REVIEW | doi:10.20944/preprints202105.0205.v1
Subject: Medicine & Pharmacology, Allergology Keywords: prostate cancer, renal cancer, urothelial cancer, vaccines, immunotherapy
Online: 10 May 2021 (14:54:43 CEST)
Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.
ARTICLE | doi:10.20944/preprints201808.0011.v1
Subject: Chemistry, Medicinal Chemistry Keywords: chitosan; aldehydes; chalcone; MIC; anti-cancer activity
Online: 1 August 2018 (09:38:35 CEST)
Versatile hybrid organic polymers are prepared using two active intermediates such as cynuric chloride and chitosan derivatives. The prepared chalcones are characterized by using FT-IR, UV, and proton NMR, thermal analysis and Minimum inhibitory Concentration. Thermal stability of the synthesized hybrid polymer is found using TGA and the hybrid chitosan derivative chalcone is thermally stable up to 270 °C. The antimicrobial activity of the prepared chitosan containing chalcone moiety are find out using Minimum Inhibitory Concentration (MIC) method. The synthesized versatile chalcone shows excellent antimicrobial activity against gram-negative bacteria such as Pseudomonas aeruginosa; and Gram-positive bacteria Chalcone containing halogen moiety shows high activity (MIC 7.8 µg/mL) than the hydroxyl containing chalcone. Cytotoxicity activity of the synthesized composites shows high activity.
REVIEW | doi:10.20944/preprints201903.0116.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: beetroot; betanins; cancer chemoprevention; anti-oxidant; inflammation; apoptosis
Online: 11 March 2019 (08:00:34 CET)
Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of aberrant gene expressions, both within the transforming cell population and the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review we discuss whereby the chemoprevention activities of the red beetroot itself may disrupt carcinogenesis and the activities of the water soluble betalains extracted from the plant.
ARTICLE | doi:10.20944/preprints201811.0629.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: bufadienolides-like chemicals; molecular mechanism; anti-cancer; bioinformatics
Online: 30 November 2018 (10:14:58 CET)
Bufadienolides-like chemicals, which mostly composed the active ingredient of Chansu, had been widely discovered to possess anti-inflammatory, tumor-suppressing and antipain activity, but the mechanisms of action were not clearly illuminated. In this research, in order to explore the potential mechanism of bufadienolides-like chemicals on breast cancer, a serious of bioinformatics analysis, included (1) differentially expressed genes identification combined with gene set variation analysis, (2) tissue specific co-expression network construction, (3) differentially regulated sub-networks detection with disease phenome, (4) hub gene selection and it’s relation to survival probability, and (5) similar small molecule detection were performed with gene expression profiles of bufadienolides-like chemicals. Results indicated bufadienolides-like chemicals had the most same target with valproic, estradiol and etc, could disturbed the pathways in RNA splicing, apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway and unfolded protein response, and had the potential ability to be used as anticancer, hormones and vasoprotectives agents.
ARTICLE | doi:10.20944/preprints202012.0032.v1
Subject: Biology, Anatomy & Morphology Keywords: Colorectal cancer; Dehydrodiisoeugenol (DEH); Autophagy inhibition; Endoplasmic reticulum (ER) stress; anti-cancer agent
Online: 1 December 2020 (14:57:00 CET)
Dehydrodiisoeugenol (DEH), a novel lignan component extracted from the Nutmeg seeds, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anti-cancer activity in gastrointestinal cancer is still to be investigated. Here, the anti-cancer effect of DEH to human colorectal cancer and its underlying mechanism were evaluated. The DEH treatment arrests the cell cycle of colorectal cancer cells at G1/S phase, which leading to a significant cell growth inhibition. Moreover, it can induce strong cellular autophagy and the autophagy would be inhibited through autophagic inhibitors with reducing EDH-induced inhibition of cell growth in colorectal cancer cells. Further studies indicated that DEH can also induce endoplasmic reticulum (ER) stress, and could subsequently stimulating autophagy through activating PERK/eIF2α and IRE1α/XBP-1s/CHOP pathways. Knockdown of PERK or IRE1α can significantly decrease the DEH-induced autophagy and retrieve cell viability in cells treated with DEH. What’s more, DEH exhibits significant anti-cancer activities through CDX- and PDX-model as well. Taken together, our studies strongly suggest that DEH might be a potential anti-cancer agent against colorectal cancer via activating ER stress-induced autophagy inhibition.
REVIEW | doi:10.20944/preprints202112.0433.v1
Subject: Life Sciences, Microbiology Keywords: Lactobacillus spp, Bacillus spp., Anti-cancer, Probiotics, Gastrointestinal, Dysbiosis.
Online: 27 December 2021 (14:50:58 CET)
Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.
REVIEW | doi:10.20944/preprints202109.0287.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: drug screening; monodrug or combinatorial drug screening; anti-cancer
Online: 16 September 2021 (13:46:49 CEST)
The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high throughput drug screening, require a small amount of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. So many attempts were performed in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.
ARTICLE | doi:10.20944/preprints201904.0299.v1
Subject: Materials Science, Biomaterials Keywords: X-ray diffraction; bioactivities; cytotoxicity test; Anti-cancer activities
Online: 26 April 2019 (11:00:21 CEST)
Owing to fascinating applications of ZnO in modern devices, it is interesting to explore its more features for future devices. Hence, herein, we have synthesized the high quality ZnO spherical nanoparticles (SNPs) through a facile green synthesis route and robust structural and biomedical studies are carried out. Hexagonal phase with 93.2% crystallinity was confirmed through XRD analysis. ZnO nanoparticles were tested for their bioactivities both in vivo (acute cytotoxicity test) and in vitro (Anti-cancer activities on liver (HepG2) and cervical (Hela) cancer cell lines, stimulatory/inhibitory effects on normal rat splenic cells and hemolytic effects on red blood cells). Results showed that ZnO SNPs has no cytotoxic effects on vital organ like liver and has no hemolytic action on red blood cells. ZnO SNPs showed inhibitory consequence on normal rat splenic cells growth at all tested concentrations. ZnO nanoparticles showed an inhibitory effect on HepG2 cell line. While showed stimulatory effect on Hela cell line. Current study presents the synthesized ZnO SNPs as highly applicable in bio-optoelectronics.
REVIEW | doi:10.20944/preprints202010.0437.v1
Subject: Life Sciences, Biochemistry Keywords: breast cancer; microbiota; bacteria; dysbiosis; pro-carcinogenic; anti-carcinogenic; genetics; next-generation sequencing; cancer treatments; cancer prevention
Online: 21 October 2020 (12:51:23 CEST)
One in eight women will be diagnosed with breast cancer (BC) in their lifetime, resulting in over 2 million cases annually. BC is the most common cancer among women. Unfortunately, the etiology of majority of cases remains unknown. Recently, evidence has shown that the human microbiota plays an important role in health and disease. Intriguingly, studies have revealed the presence of microorganisms in human breast tissue, which was previously presumed to be sterile. Next-generation sequencing technologies have paved way for the investigation of breast microbiota, uncovering bacterial signatures that are associated with BC. Some of the bacterial species were found to possess pro-carcinogenic and/or anti-carcinogenic properties, suggesting that the breast microbiota has potentially crucial roles in maintenance of breast health. In this review, we summarize the recent findings on breast tissue microbiota and its interplay with BC. Bacterial signatures identified via next-generation sequencing as well as their impact on breast carcinogenesis and cancer therapies are reviewed. Correlation of breast tissue microbiota and other factors, such as geographical and racial differences, in BC is discussed. Additionally, we discuss the future directions of research on breast microbiota as well as its potential role in prevention, diagnosis and treatment of BC.
REVIEW | doi:10.20944/preprints202004.0400.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: angiogenesis; cancer; VEGF; anticancer; vessel co-option; resistance to anti-angiogenesis treatment; cancer hallmark
Online: 23 April 2020 (04:09:02 CEST)
Angiogenesis is a term that describes the formation of new blood and lymphatic vessels from a pre-existing vasculature. This allows tumour cells to acquire sustenance in the form of nutrients and oxygen and the ability to evacuate metabolic waste. As one of the hallmarks of cancer, angiogenesis has been studied extensively in animal and human models to enable better understanding of cancer biology and the development of new anti-cancer treatments. Angiogenesis plays a crucial role in the process of tumour genesis, because solid tumour need a blood supply if they are to grow beyond a few millimeters in size. On the other hand, there is growing evidence that some solid tumour exploit existing normal blood supply and do not require a new vessel formation to grow and to undergo metastasis. This review of the literature will present the current understanding of this intricate process and the latest advances in the use of angiogenesis-targeting therapies in the fight against cancer.
REVIEW | doi:10.20944/preprints202012.0675.v1
Subject: Life Sciences, Biochemistry Keywords: Breast cancer; Estrogen Receptor; PI3K-AKT-mTOR; anti-estrogen resistance
Online: 28 December 2020 (09:22:17 CET)
Signaling from estrogen receptor alpha (ER) and its ligand estradiol (E2) is critical for growth of ~70% of breast cancers. Therefore, several drugs that inhibit ER functions are in clinical use for decades and new classes of anti-estrogens are continuously being developed. Although a significant number of ER+ breast cancers respond to anti-estrogen therapy, ~30% of these breast cancers recur, sometimes even after 20 years of initial diagnosis. Mechanism of resistance to anti-estrogens is one of the intensely studied disciplines in breast cancer. Several mechanisms have been proposed including mutations in ESR1, crosstalk between growth factor and ER signaling, and interplay between cell cycle machinery and ER signaling. ESR1 mutations as well as crosstalk with other signaling networks lead to ligand independent activation of ER thus rendering anti-estrogens ineffective, particularly when treatment involved anti-estrogens that do not degrade ERa. As a result of these studies, several therapies that combine anti-estrogens that degrade ER with PI3K/AKT/mTOR inhibitors targeting growth factor signaling or CDK4/6 inhibitors targeting cell cycle machinery are used clinically to treat recurrent ER+ breast cancers. In this review, we discuss nexus between ER-PI3K/AKT/mTOR pathways and how understanding of this nexus has helped to develop combination therapies.
ARTICLE | doi:10.20944/preprints202001.0081.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Berberine; Lipophilic substituent; Anti-cancer activity; Photocytotoxicity; Reactive oxygen species
Online: 9 January 2020 (11:30:40 CET)
The objective of this study was to synthesize 9-/13-position substituted berberine derivatives and evaluated their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e) and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in compare with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at 9-/13-position of berberine may have facilitated its penetration into test cell and hence enhanced its photocytotoxicity on human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e and 7e induced HepG2 cells to arrest at S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine (1) and its derivatives 5e, 6e and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e and 7e greatly enhanced photocytotoxicity. Taking together, the test data led us to conclude that berberine derivatives with a dodecyl group at 9-/13-position could be great candidates for the anti-liver cancer medicines developments.
REVIEW | doi:10.20944/preprints201907.0081.v1
Subject: Biology, Other Keywords: Heat shock protein 27; HSP27 inhibitor; Anti-cancer drugs, Resistance
Online: 4 July 2019 (13:19:51 CEST)
Heat shock protein 27 (HSP27), induced by heat shock, environmental, and pathophysiological stressors, is a multi-dimensional protein that acts as a protein chaperone and an antioxidant. HSP27 plays a major role in the inhibition of apoptosis and actin cytoskeletal remodeling. HSP27 is upregulated in many cancers and is associated with poor prognosis, as well as treatment resistance whereby cells are protected from therapeutic agents that normally induce apoptosis. This review highlights the most recent findings and role of HSP27 in cancer, as well as strategies for using HSP27 inhibitors for therapeutic purposes.
ARTICLE | doi:10.20944/preprints202005.0047.v1
Subject: Life Sciences, Biochemistry Keywords: tumor microenvironment; biomarkers; solid cancers; computational biology; cancer stem cells; anti-cancer stem cell therapy; chemotherapy
Online: 4 May 2020 (10:00:51 CEST)
Solid tumors display complex biology and most therapies including chemotherapy cannot prevent therapy resistance and relapse. Most therapeutics target cancer cells, but recent data suggest the presence of cancer stem cells as cells with self-renewal and tumorigenic abilities. Cancer stem cell markers have been suggested to have prognostic value and can be targeted during cancer treatment and in resistant disease. CSCs have been postulated to play significant contextual roles in tumor initiation, progression, therapy resistance and metastasis. CSCs have thus been targeted by new generation cancer drugs. The transcriptional expression of several CSC markers in different cancers was evaluated by searching publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We report here new findings on expression and prognostic significance of CSC markers in several cancers by examining the expression of CSCs markers in tumor tissues versus the adjacent normal tissues. We found that CSC markers were mostly highly expressed various tumors such as colon, lung, pancreatic and esophageal cancers. No CSC marker is expressed in the same pattern in all cancers and individual CSC marker expression was not linked to patient survival. This analysis calls for continued research on CSCs and clinical evaluation of the CSC markers in relation to prognosis of cancers in large population samples. Novel cancer drugs ought to target CSCs, cancer cells and tumor microenvironment variations.
Subject: Medicine & Pharmacology, Allergology Keywords: extracellular vesicle engineering; microRNA; loading; anti-tumor; cancer stem cells; exosomes; coincubation
Online: 10 December 2020 (10:34:42 CET)
Extracellular vesicles are considered a novel therapeutic tool, due to their ability to transfer their cargoes to target cells. Different strategies to directly load extracellular vesicles with RNA species have been proposed. Electroporation has been used for the loading of non-active vesicles, however the engineering of vesicles already carrying a therapeutically active cargo is still under investigation. We here set up a coincubation method to increase the anti-tumor effect of extracellular vesicles isolated from human liver stem cells (HLSC-EVs). Using the coincubation protocol, vesicles were loaded with the anti-tumor miRNA-145, and their effect was evaluated on renal cancer stem cell invasion. Loaded HLSC-EVs maintained their integrity and miR transfer ability, and miR-145 was protected by RNAse digestion possibly due to its binding to RNA-binding proteins on HLSC-EV surface, such as Annexin A2. Moreover, miR-145 coincubated HLSC-EVs were more effective in inhibiting the invasive properties of cancer stem cells, in comparison to naïve vesicles. The protocol reported here exploits a well-described property of extracellular vesicles to bind nucleic acids on their surface and protect them from degradation, in order to obtain an effective miRNA loading that results in the increase of the effect of naïve active extracellular vesicles.
REVIEW | doi:10.20944/preprints201808.0488.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Sarcophyton; Sinularia; Lobophytum; new compounds; anti-microbial; anti-inflammatory; anti-tumoral
Online: 29 August 2018 (09:03:48 CEST)
Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.
REVIEW | doi:10.20944/preprints202112.0525.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: colorectal cancer; immunotherapy; checkpoint blockade; adoptive cell therapy; monoclonal antibodies; oncolytic viruses; anti-cancer vaccines; cytokine; T cell; NK cell
Online: 31 December 2021 (15:14:39 CET)
Though early-stage colorectal cancer has a high 5-year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments. We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair proficient patients to immunotherapy.
ARTICLE | doi:10.20944/preprints201911.0343.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: anti-apoptosis; anti-oxidant; curcumin; hyperglycemia; hyperlipidemia
Online: 27 November 2019 (09:57:14 CET)
Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.
REVIEW | doi:10.20944/preprints201912.0342.v1
Subject: Life Sciences, Microbiology Keywords: Anti-MDR strategies; anti-persistent treatments; drug repurposing
Online: 25 December 2019 (09:33:57 CET)
Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.
ARTICLE | doi:10.20944/preprints201912.0304.v1
Subject: Mathematics & Computer Science, Information Technology & Data Management Keywords: Anti-counterfeiting; Anti-theft; RFID security; Tag cloning
Online: 23 December 2019 (12:17:40 CET)
Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.
CASE REPORT | doi:10.20944/preprints202005.0220.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: checkpoint inhibitors; tuberculosis; non-small cell lung cancer (NSCLC); Anti-PD-1; toxicity management; immunotherapy; pembrolizumab
Online: 13 May 2020 (04:38:50 CEST)
Immune checkpoint inhibitors (ICIs) – anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events have been linked to these agents. However, tuberculosis (TB) reactivation during their use is increasingly reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 Immune histochemistry (IHC) strongly positive in 95% of tumor cells. The patient presented with high-grade fever and a history of productive cough for a 1-week duration. A few days later, she was diagnosed with pulmonary tuberculosis following the 6th cycle of Pembrolizumab, an anti-PD-1 monoclonal antibody. AFB smear and TB PCR from BAL were positive (rifampin resistance not detected), and she was accordingly started on Anti-TB medications. Immunotherapy was held. Of note, the patient had a history of sick contact with a patient with active TB infection ten years ago, but there was no documentation of latent TB or previous TB infection. Her HIV status is negative. Her sputum AFB smear continued to be positive after four weeks of anti-TB medications. Later, the patient was discharged after her sputum was cleared from AFB (negative x 2 sets). We assumed that our patient developed reactivation of pulmonary tuberculosis secondary to an immune checkpoint inhibitor (Pembrolizumab). She was not re-challenged with Pembrolizumab following TB diagnosis. To our knowledge, this is the first reported case from the Arab and the Middle East; it reinforces the previous observations of the association between ICIs administration and the development of MTB. Nevertheless, further studies in the clinical setting are necessary to establish the exact mechanism involved in this association. Oncologists' awareness & prompt recognition of this potential hazardous consequence are essential. Since there is no clear evidence whether LTBT prior PD-1/PD targeted immunotherapy is required, targeted LTBT before starting ICIs immunotherapy with TB chemoprophylaxis; yet to be explored, particularly in the regions where the MTB prevalence is high.
ARTICLE | doi:10.20944/preprints202008.0077.v1
Subject: Chemistry, Medicinal Chemistry Keywords: anti-oxidant activity; anti-oxidant enzymes, anti-proliferative activity; maslinic acid; melanoma; Olea europaea; ROS levels
Online: 4 August 2020 (04:57:13 CEST)
Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.
ARTICLE | doi:10.20944/preprints202105.0546.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: triple negative breast cancer; Pembrolizumab; Atezolizumab; chemotherapy; anti-PD-L1; biomarkers; targeted therapies; development of novel drugs
Online: 24 May 2021 (09:23:50 CEST)
Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.
REVIEW | doi:10.20944/preprints202108.0328.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Phytobioactive compounds; anti-inflammatory; anti-oxidant; methotrexate; hepatotoxicity; oxidative stress
Online: 16 August 2021 (11:37:17 CEST)
Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.
ARTICLE | doi:10.20944/preprints201912.0286.v1
Subject: Materials Science, Biomaterials Keywords: Moringa oleifera; bismuth nanoparticles; polyphenolics; anti-bacterial; anti-fungal; antioxidant
Online: 21 December 2019 (12:28:21 CET)
The use of plant extracts in the synthesis of metal nanoparticles is a very attractive approach in the field of green synthesis. To benefit from the potential synergy between the biological activities of the Moringa oleifera leaves extract and metallic bismuth, our study aimed at synthesizing bismuth nanoparticles using a hydroalcoholic extract of M. oleifera leaves as a means of green synthesis that yields nontoxic products and reduces the production of wasteful material. To this end, the M. oleifera leaves extract was treated with a bismuth nitrate pentahydrate solution. A color change from light brown to dark brown indicates the synthesis of bismuth nanoparticles. The total phenolic content in the M. oleifera leaves extract used was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. Antioxidant property of MO synthesised bismuth Nanoparticles was evaluated and in line with the extract used in the synthesis of NPs. The physical properties of the synthesized bismuth nanoparticles were characterized using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized bismuth nanoparticles have a size in the range of 40.4-57.8 nm with amorphous morphology. Using DPPH and phosphomolybdate assays, our findings revealed that the M. oleifera leaves extract and the synthesized bismuth nanoparticles possess antioxidant properties. Using resazurin microtiter assay, we also demonstrate that the M. oleifera leaves extract and the synthesized bismuth nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis, similarly to the inhibition exerted by Moringa extract, especially against Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the bismuth nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized bismuth nanoparticles display relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the bismuth nanoparticles: 250, 250, 62.5, and 62.5 µg/mL, respectively). Thus, the hydroalcoholic extract of M. oleifera leaves was successfully used in the synthesis of bismuth nanoparticles, showing a positive antioxidant, anti-bacterial, and anti-fungal activity. Therefore, the synthesized bismuth nanoparticles can potentially be employed in the alleviation of symptoms associated with oxidative stress and in the topic treatment of Candida infections.
ARTICLE | doi:10.20944/preprints201911.0305.v1
Subject: Life Sciences, Microbiology Keywords: Moringa oleifera; copper nanoparticles; polyphenolics; anti-bacterial; anti-fungal; antioxidant
Online: 26 November 2019 (03:45:52 CET)
The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the anti-microbial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 μg/mL; MIC values for the cooper nanoparticles: 500, 500, 500, and 250 μg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively more potent anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 μg/mL; MIC values for the cooper nanoparticles: 125, 125, 62.5, and 31.2 μg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their potent antioxidant, anti-bacterial, and anti-fungal activities.
ARTICLE | doi:10.20944/preprints201801.0193.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: multi-agent system; decision support; anti-money laundering; anti-fraud
Online: 22 January 2018 (04:46:20 CET)
The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.
REVIEW | doi:10.20944/preprints202208.0011.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: SBSJ; polyphenolic constituents; antioxidants; anti-inflammatory, chemoprevention; immunomodulation; anti-aging; adaptogen
Online: 1 August 2022 (08:06:10 CEST)
Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.
ARTICLE | doi:10.20944/preprints201804.0100.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Cd36; mass spectrometry; NAFLD; anti-lypase activity; anti-amylase activity; insulin resistance
Online: 9 April 2018 (08:28:02 CEST)
Rhizophora mangle L. is a well-known medicinal plant found in mangroves worldwide used to treatment diabetes. This study evaluated the chemical composition of the acetonic extract from Rhizophora mangle barks (AERM), by HPLC-PDA and FIA-ESI-IT-MS/MS and the effects on high-fat diet induced obesity in mice and its mechanism of action by gene expression of inflammatory markers (Pparg, Ppara, Srebf1, Cd36, Tnf, Ccl2, Lep, Il10, Il6, Fasn, 18s). High-fat diet fed mice during 12 weeks was used as model of obesity and associated alterations. The results were very satisfactory, the extract, rich in polyphenolic compounds, flavonoids and phenolic acids, displayed intense antioxidant activity in vitro (608 µmol Trolox/g), and showed excellent activity against non-alcoholic fatty liver disease (NAFLD) and reverse insulin resistance in a model of diet-induced obesity. We can registered a modulatory effect of AERM in liver PPAR-γ mRNA expression associated to an important inhibition of CD36 mRNA expression suggesting that AERM induces the down regulation of CD36 mRNA via PPAR-gamma inhibition. These results support the traditional knowledge about the use of R. mangle for the treatment of type 2 diabetes and reveal the potential of AERM for the treatment of NAFLD and management of obesity and comorbidities.
REVIEW | doi:10.20944/preprints201805.0413.v1
Subject: Life Sciences, Other Keywords: silver nanoparticles; nanosilver; endocytosis; oxidative stress; reactive oxygen species; inflammation; wound healing; hypoxia; mitochondria; endoplasmic reticulum stress; unfolded protein response; autophagy; apoptosis; angiogenesis; epigenetics; genotoxicity; cancer; anti-cancer
Online: 28 May 2018 (15:51:12 CEST)
Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.
REVIEW | doi:10.20944/preprints202005.0003.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: Anti-platelets; Anti-rheumatic drugs; Bisphosphonates; Oral anticoagulants; Oral contraceptives; Vitamin K antagonist
Online: 2 May 2020 (11:50:24 CEST)
More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.
REVIEW | doi:10.20944/preprints201906.0042.v2
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: glucosinolate; sulphopharane; allyl isothiocyanate; phase II detoxification enzymes; anti-tumour agents; anti-bacterials.
Online: 27 July 2019 (08:40:12 CEST)
Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.
ARTICLE | doi:10.20944/preprints201805.0467.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Tspo; prostate cancer; stomach cancer; colon cancer; liver cancer; lung cancer; kidney cancer; breast cancer; brain cancer
Online: 31 May 2018 (10:59:31 CEST)
Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.
REVIEW | doi:10.20944/preprints202301.0513.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: polyacetylenes; phytochemicals; anti-inflammatory; anticancer.
Online: 28 January 2023 (03:24:05 CET)
Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of polyacetylene-rich vegetables with reduced risk of inflammation and cancer. Polyacetylene supplementation can influence cell growth, gene expression, and immunological responses, and reduce tumour number in rat and mouse models. Cancer chemoprevention by dietary polyacetylenes involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, UPR pathway, growth factor signalling, cell cycle progression, and apoptosis. This review summarises the published research on falcarinol-type polyacetylene compounds and their mechanisms of action regarding cancer chemoprevention and treatment, and also identifies some gaps in our current understanding of the health benefits of these polyacetylenes.
ARTICLE | doi:10.20944/preprints201712.0036.v1
Subject: Keywords: Sorghum bicolor leaf extract; SBLS; Jobelyn®; antioxidant; Immune-modulatory; anti-inflammatory; anti-anemia; HIV
Online: 7 December 2017 (04:37:20 CET)
The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.
REVIEW | doi:10.20944/preprints202301.0321.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Anti-inflamotry; antioxidant; oxidative stress; zebrafish
Online: 18 January 2023 (07:06:34 CET)
This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.
REVIEW | doi:10.20944/preprints202112.0014.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Pediatrics; Gait; Rehabilitation; Anti-gravity; Treadmill
Online: 1 December 2021 (12:57:48 CET)
The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.
REVIEW | doi:10.20944/preprints202001.0230.v1
Online: 21 January 2020 (03:15:50 CET)
Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.
ARTICLE | doi:10.20944/preprints201912.0060.v1
Subject: Keywords: mobile app, software quality anti-patterns
Online: 5 December 2019 (04:16:35 CET)
As the time passes the modification in technology world lead to the evaluation in mobile application as well. With evaluation in mobile industry it is an open challenge for software quality researcher that how to enhance software quality to meet the needs of changes? Quality assurance play a key role in differentiating good application from bed application. With the continuous evaluation of mobile application developing process should be quick and efficient to comply with user requirements and satisfaction. While the listed requirement leads to bad design choices known as antipatterns, which in turn affect the reliability of the code. A tool based method PAPRIKA is used in the proposed re-search to identify and monitor these antipatterns together with a two-step assessment model for software quality assurance and object oriented software quality matrix.
ARTICLE | doi:10.20944/preprints201801.0170.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Scandoside; NF-κB; MAPK; Anti-inflammation
Online: 18 January 2018 (07:03:53 CET)
The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.
ARTICLE | doi:10.20944/preprints201705.0174.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: steroid; metabolism; anti-inflammatory drug; inhibition
Online: 24 May 2017 (08:25:26 CEST)
In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.
ARTICLE | doi:10.20944/preprints202203.0236.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; BBIBP-CorV; children 3-12 years old; the anti-spike; Anti-nucleocapsid; Neutralizing antibody
Online: 16 March 2022 (15:24:51 CET)
Background and Objectives: In the current Covid-19 pandemic, children below the age of 12 could manifest Covid-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. Subjects and Methods: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. Results: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to Covid-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to Covid-19. Children with previous Covid-19 exposure had higher averages of anti-S (2379 U/ml compared to 409.1), anti-N (177.6 U/ml compared to 30.9) and neutralizing antibody (93.7 U/ml compared to 77.1) than children with no prior exposure at day 35. Conclusions: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.
REVIEW | doi:10.20944/preprints201807.0454.v1
Subject: Life Sciences, Biochemistry Keywords: Carica papaya; fermented papaya preparation (FPP); free radical scavenging; antioxidant; oxidative stress; anti-diabetic; anti-carcinogenic
Online: 24 July 2018 (11:39:50 CEST)
The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.
ARTICLE | doi:10.20944/preprints202107.0430.v1
Subject: Life Sciences, Biochemistry Keywords: Breast cancer infection; breast cancer immunity; breast cancer virus; nasopharyngeal cancer; EBV cancer; hereditary breast cancer; BRCA1; BRCA2
Online: 20 July 2021 (09:29:06 CEST)
Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, broken chromosomes may not be restored correctly, allowing breaks to persist or rearrange chromosomes. These abnormalities are potentially catastrophic events that can originate from viral infections. I used bioinformatic analyses of publicly available breast cancer patient data to show that the distribution of chromosome breaks in hereditary breast cancers differs markedly from sporadic breast cancers. Then I tested hereditary breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had decisive matches to Epstein-Barr virus (EBV / HHV4) tumor variants HKHD40 and HKNPC60. Many breakpoints were near EBV genome anchor sites, human EBV tumor-like sequences, EBV-associated epigenetic marks, and some fragile sites. On chromosomes 2 and 12, sequences near EBV genome anchor sites accounted for 90% and 88% of breakpoints (p<0.0001), respectively. On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences in 19 hereditary breast cancers. In contrast, 19 sporadic breast cancers only had 12 interchromosomal breakpoint regions on chromosome 4 near EBV-like sequences. On various other chromosomes, five EBV genome anchor sites were near hereditary breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Independent evidence further implicating EBV in hereditary breast cancer breakpoints is that 25 breast cancer break positions are within 1.25% of breakpoints in model EBV cancers. In addition to BRCA1 or BRCA2 mutations, all the hereditary breast cancers had mutated genes essential for immune responses. This compromise facilitates reactivation of herpes viruses which produce nucleases capable of breaking chromosomes. EBV also causes other deleterious effects: anchored EBV episomes can interfere with normal replication and obstruct DNA break repairs; even very early infection causes massive transcription changes. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.
REVIEW | doi:10.20944/preprints201709.0069.v1
Subject: Life Sciences, Biochemistry Keywords: Glyoxalases; urological malignancies; prostate cancer; kidney cancer; bladder cancer testicular cancer
Online: 15 September 2017 (14:28:24 CEST)
Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide and although advances have been made toward understanding the molecular basis of these diseases, a complete insight of the pathogenic mechanisms is still a research challenge for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these neoplasms for which no effective therapies exist. Glyoxalases are enzymes that catalyzes the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggest that glyoxalases, especially Glo1, would act as oncogenes in urological malignancies and be central to their initiation, growth and progression. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-PCa therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.
Online: 2 November 2020 (13:50:43 CET)
Epidemiological studies on micronutrient consumption have reported protective associations in the incidence and/or progression of various cancer types. Supplementation with some of these micronutrients has been analyzed, showing chemoprotection, low toxicity, antiproliferation, and the ability to modify epigenetic signatures in various cancer models. The following review inves-tigates the reported effects of micronutrient intake or supplementation in breast cancer progres-sion. A PubMed search was conducted with the keywords “micronutrients breast cancer progres-sion,” and the results were analyzed. The selected micronutrients were: Vitamins (A, C, D, and E), Folic Acid, metals (Cu, Fe, Se, and Zn), fatty acids, polyphenols, and iodine. The majority of in vitro models showed antiproliferative, cell cycle arrest, and antimetastatic effects for almost all the micronutrients analyzed, but these effects do not reflect animal or human studies. Only one clinical trial with Vitamin D and one pilot study with molecular iodine showed favorable overall survival and disease-free interval.
REVIEW | doi:10.20944/preprints201807.0525.v2
Subject: Medicine & Pharmacology, Gastroenterology Keywords: 4-Hydroxynonenal; lipid peroxidation; redox balance; oxidative stress; stomach; peptic ulcer; gastritis; Helicobacter pylori; gastric cancer; non-steroid anti-inflammatory drugs-induced gastropathy
Online: 23 August 2018 (04:24:43 CEST)
Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.
ARTICLE | doi:10.20944/preprints202210.0470.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: metastasis; cancer evolution; bioinformatics; cancer biology; cancer genomics
Online: 31 October 2022 (07:06:45 CET)
: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.
Subject: Medicine & Pharmacology, Allergology Keywords: Cancer; Cancer Prevention; Cancer Therapy; Immune Boosting Interventions
Online: 30 April 2021 (15:52:40 CEST)
Cancer risk is known to increase tremendously when the immune system is suppressed, e.g., as observed in young organ-transplant recipients and AIDS patients. Based on such data, it may be hypothesized that the main reason for the development of clinical cancer is the weakening or suppression of the immune system, and that uncontrolled multiplication of cancer cells occurs when some aspects of the immune system fall below certain critical levels. Therefore, cancer may be prevented and treated by boosting these critical aspects of the immune system so that they are maintained above the critical levels. If multiple immune system boosting interventions are utilized, more aspects of the immune system would be boosted, increasing the likelihood of enhancing the critical aspects of the immune system and generating a cancer preventive and/or therapeutic effect. Clinical trials are needed to validate this approach for cancer prevention and treatment. If validated, the proposed approach could result in a major reduction of the death and suffering caused by cancer in the world.
ARTICLE | doi:10.20944/preprints202211.0089.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Tibouchina granulosa; anti-inflammatory activity; hispiduloside; cytokines
Online: 4 November 2022 (07:24:02 CET)
The ethanol extract (EE) prepared from the leaves of Tibouchina granulosa, and its fraction in ethyl acetate (fEA) were evaluated concerning their capacity to reduce inflammation in different experimental models. fEA was also studied concerning its chemical constituents. EE and fEA were assayed for their anti-inflammatory potential, using formalin-induced licking behaviour and carrageenan-induced inflammation into the subcutaneous air pouch (SAP) models. Reduction in polymorphonuclear cells (PMN) activation was performed in freshly isolated PMN. Chromatographic analysis of fEA was done by HPLC. Hispiduloside was isolated as the main constituent in fEA and its quantity was estimated to be 11.75% in fEA, 3.05% in EE, and 0.2% (w/w) in the plant. EE (30 mg/kg) significantly reduced the second phase of formalin-induced licking. fEA demonstrated a reduction in leukocyte migration into the SAP. EE and fEA drastically reduced cytokines (TNF-α, IL-1β, and IFN-γ), nitric oxide (NO) production, in vitro PMN migration induced by C5a and IL-8, and TNF-α and IL-1β gene expression. Taken together our data indicate that either ethanol extract or its fEA fraction from leaves of T. granulosa present an anti-inflammatory effect contributing to the pharmacological and chemical knowledge of this species and confirming the rationale behind its traditional use.
ARTICLE | doi:10.20944/preprints202111.0541.v1
Subject: Life Sciences, Biotechnology Keywords: Codium fragile; marine algae; anti-obesity; prebiotics
Online: 29 November 2021 (14:51:07 CET)
Polysaccharides from marine algae exhibit beneficial biological activities. In this study, we examined the effect of polysaccharides from Codium fragile (PCF) on prebiotic and anti-obesity activity. PCF increases the growth of specific beneficial microbial populations with concomitant decrease in pathogenic microbes. Further, total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH activity) after fermentation with PCF as carbon source were higher than for the glucose as control. Moreover, PCF inhibited adipocyte differentiation by inducing differentiation-related factors when the induction of 3T3-L1 preadipocytes into adipocytes was induced. Therefore, we suggest that PCF can be used as prebiotic material with anti-obesity for human health.
REVIEW | doi:10.20944/preprints202108.0200.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: antioxidant; anti-inflammatory; cardiovascular; Channa striatus; diabetes
Online: 9 August 2021 (14:59:08 CEST)
Diabetes mellitus remains a major risk factor for developing cardiovascular diseases, resulting in increased morbidity and mortality associated with cardiovascular complications. Given the burden of diabetes-related cardiovascular complications, there is a need to identify strategies, safe and effective therapeutic agents that could effectively prevent and control diabetes. Presently, many patients living with diabetes depends on traditional medicines as an alternative cure. Channa striatus (Haruan) is a freshwater fish traditionally used to treat wounds, inflammations, and pains. Several pharmacological investigations have supported the folkloric claims of C. striatus extracts, including hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory, and pro-platelet aggregation activities. The therapeutic potentials of C. striatus were demonstrated to be associated with the presence of high content essential amino acids and good fatty acids known to improve cell growth and facilitate wound healing. Therefore, C. striatus bioactive compounds have great potentials to serve as lead candidates in developing novel therapeutic agents for the management of diabetes and related cardiovascular diseases. This review aims to provide a comprehensive overview of the pharmacological properties and therapeutic potentials of C. striatus for the management of diabetes and associated cardiovascular complications.
REVIEW | doi:10.20944/preprints202106.0620.v1
Subject: Medicine & Pharmacology, Allergology Keywords: adipogenesis; signaling pathways; anti-obesity treatment; obesity
Online: 25 June 2021 (12:09:51 CEST)
Abstract: As a risk factor, obesity is a threat to human well-being and related metabolic disorders such as diabetes mellitus and dyslipidemia. adipogenesis is defined as the proliferation and maturation of adipocyte predecessor cells to adipocyte. As the adipogenesis process decides adipocyte production, it may be considered a therapeutic target for obesity and obesity-related disorders. White adipose tissue abnormal expansion increases the size and number of adipocytes. For that reason, this review aims to spot the molecular mechanisms implicated in adipogenesis that lead to application in the therapeutic targets. Keywords: adipogenesis, signaling pathways, anti-obesity treatment, obesity
ARTICLE | doi:10.20944/preprints202102.0013.v1
Subject: Social Sciences, Accounting Keywords: anti-globalization; economic globalization; US-dominated globalization
Online: 1 February 2021 (11:28:16 CET)
Since the financial crisis in 2008, the U.S. economy has weakened, and the world economy has slowly developed. As the world's leading country, the United States has used many methods to restore the economy. But it does work efficiently. However, there are many issues in developed countries such as domestic social, economic, immigration in the United States/United Kingdom; those are not optimistic. Developed countries have entered a dilemma. The neoliberalism financial system has been unable to move forward. Populists have pointed out that those problems have been causing by globalization. Under the leadership of the Brexit Referendum, President Trump has caused a wave of anti-globalization. Under a series of systems such as the China-US trade war and the US-Mexico border wall repairs, the anti-globalization trend is getting stronger. This article mainly analyzes the in-depth reasons and mechanism research of globalization and anti-globalization alternately—the data obtained from an international method performance study. The results show that anti-globalization is temporary, along with globalization. There are three main factors affecting globalization: the situation of the dominant country, natural disasters, and wars. After so much literature review, I believe that the United States' globalization is gradually weakening, and globalization may return to regionalization under the United States' opposition.
ARTICLE | doi:10.20944/preprints202007.0360.v2
Online: 10 August 2020 (15:16:58 CEST)
Product counterfeiting is an on-going problem in supply chains and retail environments, Recently an anti-counterfeiting protocol to address this issue via cost-effective use of auto-identification technologies such as radio-frequency identification (RFID) was proposed by researchers.Yet the use case of re-selling the same product was not been fully addressed which might cause serious problem for the exciting and proposed schemes and transactions. This paper proposes an extended RFID-based anti-counterfeiting to address the use case of the original buyer reselling the same item to a second buyer. The extended scheme will be followed by a formal security analysis to show that the proposed protocol satisfies the requirements of security correctness and is resistant to compromise through security attacks.
COMMUNICATION | doi:10.20944/preprints202005.0270.v1
Online: 16 May 2020 (16:51:36 CEST)
A novel approach has been suggested to use isoelectric points of viral and human proteins to quickly identify proteins that are effective in not allowing virus particles to attach to human receptor cells by virtue of their electrical charge. The method has been applied to SARS CoV-2 to suggest potentially important human proteins that can be suitable for making anti-viral drugs.
REVIEW | doi:10.20944/preprints201812.0063.v1
Online: 5 December 2018 (07:40:27 CET)
Chaenomeles plants are adapted to diverse ecological zones particularly the temperate areas of Korea, Japan and China. In China, Chaenomeles speciosa mainly planted in Chongqing, Anhui and Hubei provinces. Most of the studies till date have been focused on the anti-inflammatory activities of C. speciosa fractions. The present study aimed to review the maximum literature reported for the presence of various phytochemicals in C. speciosa. In addition, the pharmacological properties of these chemical compounds of this plant shall also be discussed. The extracts of the various parts of the plant are rich in diversity of antioxidants, organic acids, phenolics, terpenoides and many different phytochemicals that bear strong anticancer, antioxidant, anti-viral, antibacterial properties, anti-inflammation, anti-hyperlipidemic, anti-hyperglycemic and anti-parkinson properties. C. speciosa fruits have broad scope in industry as well as in medicines. Not only the leaves and fruits of C. speciosa plant, but various other parts including roots, seeds, bark twigs, and flowers all have long history of clinical trials in curing many human ailments. However, the maximum accessible data concerning the chemical composition and their broad pharmacological properties of C. speciosa plant parts is pretty restricted that make it more appealing for indepth investigations.
ARTICLE | doi:10.20944/preprints201809.0323.v1
Online: 17 September 2018 (16:11:45 CEST)
Fracking in the UK has yet to reach full industrial development but it is still subject to significant opposition. This study uses Beck’s Risk Society theory and anti-politics to examine the views voiced by opponents to fracking in Yorkshire, England. A qualitative approach was used; local newspaper reports were evaluated alongside semi-structured interviews with protesters to provide a thematic analysis. Although there are signs of post-materialist concerns with the environment these issues did not dominate the discussion. Scientists were not held responsible for the risks involved in fracking. Instead economic greediness of politicians and austerity measures were perceived as putting the environment and people’s health at risk. Interviewees thought fossil fuel energy production was economically advantaged over more sustainable energy and jobs in the low carbon economy. Protesters’ trust in politicians had been eroded but faith in democracy remained. It is suggested a citizen-led deliberative approach to all the concerns raised, not simply those relating to scientific risk, might achieve some level of resolution over fracking in the UK.
ARTICLE | doi:10.20944/preprints201809.0282.v1
Online: 16 September 2018 (10:02:14 CEST)
Background. Nanotechnology is promising field for generating new applications. A green synthesis of nanoparticles through biological methods using plant extract have a reliable and ecofriendly approach to improve our global environment. Methods. Silver nanoparticles (AgNPs) were synthesized using aqueous extract of Anagalis arvensis L and silver nitrate and were physicochemically characterized. Results. The stability of AgNPs toward acidity, alkalinity, salinity and temperature showed that they remained stable at room temperature for more than two months. The SEM and TEM analysis of the AgNPs showed that they have a uniform spherical shape with an average size in the range of 40–78 nm. Further 1-Dibhenyl-2-Picrylhydrazl radical in Anagalis arvensis L.mediated AgNPs showed a maximum activity of 98% at concentration of 200μg/mL. Hydrogen peroxide scavenging assay in Anagalis arvensis L. mediated AgNPs showed a maximum activity of 85% at concentration of 200μg/mL. Reducing power of Anagalis arvensis L.Ag NPs exhibited a higher activity of 330 μg/mL at concentration of 200 μg/mL. These NPs have cytotoxic effects against brine shrimp (Artemia salina) nauplii with a value of 53% LD 178.04μg/mL. Conclusion. The AgNPs synthesized using Anagalis arvensis L. extract demonstrate a broad range of applications.
ARTICLE | doi:10.20944/preprints201805.0455.v1
Subject: Chemistry, Analytical Chemistry Keywords: Gonocaryum calleryanum; secoiridoid; structure identification; anti-inflammatory.
Online: 30 May 2018 (16:42:36 CEST)
Three new secoiridoid constituents Gonocarin A-C (1-3) and a new derivative Gonocarin A monoacetate (4), along with two known lignins pinoresinol (5) and paulownin (6) were isolated from the seed of Gonocaryum calleryanum (Baill.) Becc. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy. When mouse macrophages RAW264.7 were treated with compounds 1-6 together with LPS -stimulated, a concentration-dependent inhibition of nitric oxide (NO) and tumor necrosis factor (TNF-α) productions were detected. The results confirmed that the Gonocaryum calleryanumrrg could be a potential anti-inflammatory agent.
ARTICLE | doi:10.20944/preprints201804.0033.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: cordycepin; adenosine A1 receptor; prolactin; anti-obesity
Online: 3 April 2018 (07:53:24 CEST)
Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A1 receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.
ARTICLE | doi:10.20944/preprints201705.0208.v1
Subject: Biology, Physiology Keywords: oligonol; diabetes; pancreas; antioxidative stress; anti-inflammation
Online: 30 May 2017 (06:29:46 CEST)
Oligonol is a low-molecular-weight polyphenol derived from lychee fruit. This study was conducted to examine whether oligonol has an ameliorative effect on diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and changes in serum glucose, C-peptide, insulin, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) levels as well as body weight and food and water consumption were assessed. Furthermore, rat pancreases were analyzed for weight, ROS generation, TBARS level, insulin content, and protein expressions of phosphor (p)-p38, p-extracellular-signal regulated kinase 1/2, p-inhibitor of nuclear factor kappa Bα, nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Markers of diabetes were shown to be decreased by oligonol administration and histological damage in the pancreas was also ameliorated. These results indicate that oligonol exerts antidiabetic activities, which may be mediated via antioxidative, stress-related, anti-inflammatory signaling.
ARTICLE | doi:10.20944/preprints201611.0023.v1
Subject: Life Sciences, Other Keywords: anti-yeast; enzyme inhibitors; Terminalia mantaly; Combretaceae
Online: 3 November 2016 (09:35:17 CET)
The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC50 values below 4 µM and inhibitory constant (Ki) <3 µM.
REVIEW | doi:10.20944/preprints202203.0107.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Nanobiotechnology; Biomarkers; Biosensors; Lung cancer; Skin Cancer; Colorectal Cancer
Online: 7 March 2022 (15:03:00 CET)
In the era of nanotechnology, researchers are implementing point to care service to cancer patients to detect malignancy beforehand and to reduce the mortality rate of cancers. Cancer is known to be the most fatal disease among all other diseases and the survivability from cancer is quite impossible if the stage of the cancer is an advanced level. Though the early detection of cancer can increase the chances of survival with a double fold. Biosensor is a part of nanotechnology which is capable to provide point to care service in the field of medicine. With the rising number of cancer occurrences being identified around the world and the increasing number of deaths because of the identification of advanced cancer, biosensors can play a significant part in the early detection of cancer. New molecular methods, including as genomic and proteomic approaches, are increasingly being used to study patient molecular profiles. When such diagnosis method is paired with bioinformatics tools, they generate new data that can be used to discover new disease biomarkers. Finding precise and sensitive indicators that are corelated to a specific disease, as with many other diseases, can be challenging. Furthermore, the concentration of biomarkers in biological fluids varies according to illness states and phases. Peptides, proteins, up or down regulated expression of gene markers, and gene alternation are all examples of molecular markers that are commonly used to diagnose cancer. In this article, we have highlighted six different deadliest cancers such as Ovarian, Breast, Prostrate, Lung, Colorectal and Liver cancer. The article contains distinct types of biomarkers which are normally found in these kinds of cancer and generally used as a potential diagnostic target in the medicine field. The article mainly summarized the application of different types of biosensors devices in the detection of the mostly found biomarkers in the above cancer types.
REVIEW | doi:10.20944/preprints202007.0029.v1
Online: 3 July 2020 (09:05:13 CEST)
Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.
ARTICLE | doi:10.20944/preprints201803.0044.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cancer prevention; carcinogenesis; oral cancer; pharynx cancer; mouthrinses; ethanol.
Online: 6 March 2018 (14:28:22 CET)
Objective: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol containing mouthwashes and oral cancer.Methods: Human epithelial keratinocytes were exposed for 30 seconds to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.Results: A marked cytotoxic effect was observed for ethanol concentrations of 20% and above. Conclusions: The cytotoxicity of ethanol can explain the epidemiological association between mouthwash use and oral cancer. Recent findings indicate that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, we will force the stem cells of the oral cavity to divide more often than usual and our risk of developing oral cancer will probably increase.Clinical significance: Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol containing mouthwashes when advising their patients.
ARTICLE | doi:10.20944/preprints201808.0307.v3
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Immune Checkpoint Inhibitors; anti-PD-1/PDL-1; anti-CTLA-4; gender; sex; Nivolumab; Pembrolizumab; Atezolizumab; Ipilimumab; Durvalumab
Online: 15 November 2018 (07:02:24 CET)
Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p<0.001 and HR 0.77, p<0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p<0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p<0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.
ARTICLE | doi:10.20944/preprints202212.0399.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Amino acids, lipids, diet, low-fat diet, cancer therapy, cancer metabolism, triple-negative breast cancer, lung cancer, melanoma, colorectal cancer, ovarian cancer, metastasis
Online: 21 December 2022 (10:05:50 CET)
Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.
ARTICLE | doi:10.20944/preprints202210.0369.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Covid-19; health literacy; cancer screening; cancer care; cancer prevention
Online: 25 October 2022 (02:02:04 CEST)
The COVID-19 pandemic has led to numerous delays in cancer-related care and cancer-specific screening, but the extent is not fully understood. For those that experience a delay or disruption in care, health related self-management is required to re-engage in care pathways and the role of health literacy in this pathway has not been explored. The purpose of this analysis is to (1) report the frequency of self-reported delays in cancer treatment and preventative screening services at an academic, NCI-designated center during the COVID-19 pandemic and (2) investigate cancer-related care and screening delays among those with adequate and limited health literacy. A cross-sectional survey was administered from an NCI-designated Cancer Center with a rural catchment area during November 2020 through March 2021. Nearly 19 percent of participants were categorized as having limited health literacy. Twenty percent of those with a cancer diagnosis reported a delay in cancer-related care; and 23-30% of the sample reported a delay in cancer screening. In general, the proportions of delays among those with adequate and limited health literacy were similar with the exception of colorectal cacner screening. There was also a notable difference in the ability to re-engage in cervical cancer screening among those with adequate and limited health literacy. Thus, there is a role for those engaged in cancer-related education and outreach to offer additional navigation resources for those at risk to cancer-related care and screening disruptions. Future study is warranted to investigate the role of health literacy on cancer care engagement.
ARTICLE | doi:10.20944/preprints202203.0176.v2
Subject: Behavioral Sciences, Other Keywords: colorectal cancer screening; breast cancer screening; BC; CRC; cancer prevention; cancer screen-ing; FOBT; mammography; Flanders
Online: 20 May 2022 (12:03:16 CEST)
Despite the recognized benefits of fecal occult blood test (FOBT) and mammography screenings, participation in breast (BC) and colorectal cancer (CRC) screening programs is still suboptimal. This study investigates municipal characteristics associated with their BC/CRC screening uptake profiles among women aged 55–69 years. Using data from 308 municipalities of Flanders from 2014 to 2017, a profile for each municipality based on its BC/CRC screening uptake compared with the median screening uptake was created. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and BC/CRC screening uptake profiles. The overall median uptake of cancer screening was higher for CRC (57.4%) than for BC (54.6%). The following municipal characteristics were associated with worse performance in terms of only CRC, only BC, or both CRC and BC screening uptake, respectively: foreign nationality, self-employment rate, (early) retirement rate, diabetes, disabilities; (early) retirement rate; age group 65–69, foreign nationality, self-employment rate, (early) retirement rate, wage-earners, diabetes. The following municipal characteristics were associated with better performance in terms of only CRC, only BC, or both CRC and BC screening uptake respectively: residential stability, having a partner, having children, jobseeker rate, GP visits, preventive dental visits; having children, GP visits; age group 55–59, residential stability, having a partner, having children, jobseeker rate, higher education, GP visits, preventive dental visits. This study’s results regarding the interrelation between the BC and CRC screening could be used to tailor interventions to improve the participation of the target population in both programs.
ARTICLE | doi:10.20944/preprints202010.0590.v1
Subject: Medicine & Pharmacology, Allergology Keywords: burden of cancer mortality; cancer epidemiology; cancer etiology; cancer prevention; carcinogenic infections; modifiable risk factors
Online: 28 October 2020 (12:13:01 CET)
Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy was still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group-1 carcinogenic agents in humans by IARC. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was on average 8.7% of all cancer deaths registered yearly. Approximately 60% of deaths occurred in men and almost the whole burden was due to four infectious agents (Helicobacter pylori, HCV, HPV, and HBV). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.
ARTICLE | doi:10.20944/preprints202105.0490.v1
Subject: Life Sciences, Biochemistry Keywords: Breast cancer infection; breast cancer immunity; breast cancer virus; genome biochemistry; nasopharyngeal cancer; herpes viruses; hereditary breast cancer; BRCA1; BRCA2; Burkitt's lymphoma; homologous recombination; DNA repair; viral cancer; chromosome breaks; Breast cancer infection; breast cancer immunity; breast cancer virus; nasopharyngeal cancer; hereditary breast cancer; BRCA1; BRCA2; Burkitt's lymphoma
Online: 20 May 2021 (12:43:11 CEST)
Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, chromosome fragments may not be restored correctly. Resulting chromosome rearrangements can become critical breast cancer drivers. Because I had data from thousands of cancer structural alterations that matched viral infections, I wondered whether infections contribute to chromosome breaks and rearrangements in hereditary breast cancers. There are currently no interventions to prevent chromosome breaks because they are thought to be unavoidable. However, if chromosome breaks come from infections, they can be treated or prevented. I used bioinformatic analyses to test publicly available breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had the strongest matches to Epstein-Barr virus (EBV) tumor variants HKHD40 and HKNPC60. Many breakpoints were near sites that anchor EBV genomes, human EBV tumor-like sequences, EBV-associated epigenetic marks, and fragile sites. On chromosome 2, sequences near EBV genome anchor sites accounted for 90% of breakpoints (p<0.0001). On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences. Five EBV genome anchor sites were near breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Breakpoint flanking regions resembled known EBV-cancers. Twenty-five breakpoints in breast cancers were within 1.25% of EBV cancer breakpoints. In addition to BRCA1 or BRCA2 mutations, all the breast cancers had mutated genes essential for immune responses. Because of this immune compromise, herpes viruses can activate and produce nucleases that break chromosomes. Alternatively, anchored viral episomes can obstruct break repairs, whatever the cause. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.
ARTICLE | doi:10.20944/preprints202208.0088.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Amino acids; cancer; cancer metabolism; cancer therapy; kidney cancer; renal adenocarcinoma; renal cancer; metastasis; selective amino acid restriction therapy; restriction
Online: 3 August 2022 (11:16:39 CEST)
Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.
EDITORIAL | doi:10.20944/preprints201608.0130.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: carcinogenesis; cancer; age distribution of cancer
Online: 11 August 2016 (11:40:40 CEST)
Tobacco use, most people would say. Smoking tobacco increases the risk of developing many types of cancer and is responsible for approximately one-third of all cancer deaths. The association between tobacco use and lung cancer is well known; lung cancer occurs about 20 times more often in heavy smokers than in nonsmokers . However, many lung cancers are diagnosed in never smokers , and most smokers do not develop lung cancer [3,4].
REVIEW | doi:10.20944/preprints202208.0008.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: influenza; antivirals; anti-influenza; influenza drugs; the flu
Online: 1 August 2022 (05:41:34 CEST)
Antigenic drift in influenza strains allows viruses to avoid being fully suppressed by seasonal vaccines. As a result, public interest has led to increased scrutiny and reevaluation of anti-influenza antiviral drugs as possible solutions. Unfortunately, many anti-influenza drugs developed around the globe suffer from a lack of sufficient clinical trials, as well as a lack of toxicity data. This is especially true of Arbidol, a popularly used drug for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, which were developed in the United States, also fall victim to inconclusive clinical trials and adverse effects. Adamantanes, while proven to be effective in treating influenza A, are encountering rapid, widespread cross-resistance. Baloxavir marboxil, a newer anti-influenza medication, shows promise in treating acute uncomplicated influenza, and may avoid the development of resistance when coadministered with other antiviral drugs. This review explores the antivirals available for influenzas treatment at this time.
ARTICLE | doi:10.20944/preprints202207.0258.v1
Subject: Biology, Physiology Keywords: Melatonin; glial scar; insertion trauma; anti-inflammatory; antioxidant
Online: 18 July 2022 (10:08:28 CEST)
Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the implant site have been shown to decrease with chronic administration of antioxidant melatonin at week 16, but its effects on the acute landscape have not been studied. To assess the effect of melatonin administration in the acute phase, specifically the first week post-implantation, we utilized histological and q-PCR methods to quantify cellular and molecular indicators of inflammation and oxidative stress as well as two-photon microscopy to track the microglial responses in real-time. Histological results indicate that melatonin effectively maintained neuron density surrounding the electrode, inhibited accumulation and activation of microglia, astrocytes, and reduced oxidative tissue damage. The expression of the pro-inflammatory cytokines, TNF-α and IL-6, were significantly reduced in melatonin-treated animals. Additionally, microglia encapsulation of the implant surface was inhibited by melatonin as compared to control animals following implantation. Our results combined with previous research suggest that melatonin is a particularly suitable drug for modulating inflammatory activity around neural electrode implants both acutely and chronically, translating to more stable and reliable interfaces.
REVIEW | doi:10.20944/preprints202207.0040.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Kalanchoe; antibacterial; anti-inflammatory properties; wound healing; antioxidant
Online: 4 July 2022 (08:27:24 CEST)
The Kalanchoe genus is composed of more than 100 species that usually thrive in tropical environments, which have been used in folkloric medicine to treat various illnesses, including dermatological conditions. With this, the present study assesses the pharmacognostical and pharmacological properties of different species of the Kalanchoe genus as elements for a potential treatment for dermatological-related conditions, from findings of existing literature and studies. It was analyzed that the Kalanchoe pinnata plant, or one of the most common species of Kalanchoe, have been observed to have distinct morphological and microscopic characteristics. Further, it was discovered that different species of Kalanchoe have anti-inflammatory, antioxidant, antibacterial, and wound healing properties, which enable the plant to be used for dermatological products that are available to the market. With this, it is recommended that further studies be conducted in other understudied species of Kalanchoe regarding their pharmacological properties, as well as the use of other structures of the Kalanchoe plant for treatment of various dermatological conditions.
REVIEW | doi:10.20944/preprints202105.0625.v1
Online: 26 May 2021 (08:17:01 CEST)
Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.
ARTICLE | doi:10.20944/preprints202101.0204.v1
Subject: Biology, Plant Sciences Keywords: Antioxidant; Anti-inflammatory; Chitosan; Flavonoids; Phenolics; Silybum marianum
Online: 11 January 2021 (15:59:31 CET)
Silybum marianum (L.) Gaertn is a rich source of antioxidants and anti-inflammatory flavonolignans with great potential for use in pharmaceutical and cosmetic products. Its biotechnological production using in vitro culture system has been proposed. Chitosan is a well-known elicitor that strongly affects both secondary metabolites and biomass production by plants. The effect of chitosan on S. marianum cell suspension is not known yet. In the present study, suspension cultures of S marianum were exploited for their in vitro potency to produce bioactive flavonolignans in the presence of chitosan. Established cell suspension culture was maintained on the same hormonal media supplemented with 0.5 mg/L BAP (6-benzylaminopurine) and 1.0 mg/L NAA (α-naphthalene acetic acid) under photoperiod 16/8 h (light/dark) and exposed to various treatments of chitosan (ranging from 0.5 to 50.0 mg/L). The highest biomass production was observed for cell suspension treated with 5.0 mg/L chitosan, resulting in 123.3 g/L fresh weight (FW) and 17.7 g/L dry weight (DW) productions. Chitosan treatment resulted in an overall increase in the accumulation of flavonoids, phenolic compounds and silymarin. High accumulation levels of silybin B, silydianin and silybin A were recorded by HPLC analysis. The corresponding extracts displayed interesting antioxidant and anti-inflammatory capacities. In particular, high ABTS antioxidant activity (741.5 μM Trolox C equivalent antioxidant capacity) was recorded in extracts obtained in presence of 0.5 mg/L of chitosan. On the opposite, highest inhibitions of cyclooxygenase 2 (COX-2, 30.5 %), secretory phospholipase A2 (sPLA2, 33.9 %) and 15-lipoxygenase (15-LOX-2, 31.6 %) enzymes involved in inflammation process were measured in extracts obtained in presence of 5.0 mg/L of chitosan. Taken together, these results highlight the high potential of the chitosan elicitation of the S. marianum cell suspension for enhanced production of antioxidant and anti-inflammatory silymarin-rich extracts.
ARTICLE | doi:10.20944/preprints202012.0340.v1
Subject: Keywords: helminth; helminthic therapy; biological therapy; inflammation; anti-inflammatory
Online: 14 December 2020 (13:40:28 CET)
The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical in moving the field forward into mainstream medicine.
ARTICLE | doi:10.20944/preprints202011.0611.v1
Subject: Life Sciences, Biochemistry Keywords: cyanobacteria; thermal mud; natural products; anti-inflammatory; bioactivity
Online: 24 November 2020 (10:53:33 CET)
Background: The Balaruc-les-Bains’ thermal mud was found to be colonized predominantly by microorganisms, with cyanobacteria constituting the primary organism in the microbial biofilm observed on the mud surface. The success of cyanobacteria in colonizing this specific ecological niche can be explained in part by their taxa-specific adaptation capacities, and also the diversity of bioactive natural products that they synthesize. This array of components has physiological and ecological properties that may be exploited for various applications.
ARTICLE | doi:10.20944/preprints202011.0446.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Alkaloids; Anti-Onchocercal; Bisindoles; Docking; Homology Modeling; Monoindoles.
Online: 17 November 2020 (11:13:54 CET)
A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds, voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8), and conoduramine (9), were isolated from the stem bark of Voacanga africana. The structures of the compounds were determined by comprehensive spectroscopic analyses (1D- and 2D-NMR). Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC50 values of the isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. Homology modeling was used to generate a 3D model of the the O. ochengi thioredoxin reductase target and docking simulation attempted to offer an explanation of the anti-onchocercal structure-activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilirial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.
Online: 22 October 2020 (12:41:30 CEST)
Fibrosis is a condition characterized by thickening or/and scarring of various tissues. Fibrosis may develop in almost all tissues and organs, and it may be one of the leading causes of morbidity and mortality. It provokes excessive scarring that excels the usual wound healing response to trauma in numerous organs. Currently, very little can be done to prevent tissue fibrosis, and it is almost impossible to reverse it. Therefore, fibrosis is frequently associated with premature aging. In turn, aging is associated with more frequent incidences of fibrosis. Anti-inflammatory and immunosuppressive drugs are among the few treatments that may be efficient in preventing fibrosis. Numerous publications suggest that cannabinoids and extracts of Cannabis sativa have potent anti-inflammatory and anti-fibrogenic properties. In this review, we describe the types and mechanisms of fibrosis in various tissues and discuss various strategies for prevention and dealing with tissue fibrosis. We further introduce cannabinoids and their potential for the prevention and treatment of fibrosis, and therefore for extending healthy lifespan.
ARTICLE | doi:10.20944/preprints202008.0443.v1
Subject: Biology, Plant Sciences Keywords: cell suspension culture; anti-inflammatory activity; phytochemical analysis
Online: 20 August 2020 (07:44:18 CEST)
Many species of the Asteraceae family are used in traditional Mexican medicine for possessing healing properties. Ageratina pichinchensis (Asteraceae) is a plant used for the treatment of gastric ulcers, deep wounds and for its antifungal effects. The aim of this study was to establish a cell suspension culture of A. pichinchensis, quantify the anti-inflammatory constituents 2,3-dihydrobenzofuran and 3-epilupeol, to evaluate the anti-inflammatory potential of its extracts and perform a phytochemical analysis. Cell suspension cultures were established in MS culture medium supplemented with 30 g L-1 sucrose and 1.0 g L-1 α-naphthaleneacetic acid (NAA) plus 0.1 mg L-1 6-furfurylaminopurine (KIN). The ethyl acetate extracts of cell suspension cultures analyzed by GC revealed that the maximum production of compounds The anti-inflammatory activity of these extracts exhibited significant inhibition of NO production. Furthermore, the phytochemical study of EtOAc and MeOH extracts of the biomass on day 20 led to the identification of 17 known compounds. The structures of compounds were assigned by analysis of 1D and 2D NMR data and the remainder by GC-MS. This is the first report of the production of the (-)-Artemesinol, (-)-Artemesinol glucoside, Encecalin and 3,5-diprenyl-acetophenone compounds by a cell suspension cultures of A. pichinchensis.
ARTICLE | doi:10.20944/preprints201904.0178.v1
Subject: Chemistry, Applied Chemistry Keywords: anti-oxidative properties; DPPH; grape marmalade; lactobacillus; probiotics
Online: 16 April 2019 (10:27:52 CEST)
Grape foods fermented with probiotics are sources of beneficial bacteria for the GI tract and also have a high antioxidant capacity. The addition of probiotics to ferment food has always been a traditional process; therefore, probiotic dairy and non-dairy products might contribute to a daily antioxidant diet to improve consumers’ life quality and health. This research was undertaken to determine the viability of 4 wild isolates of Lactobacillus for storage at 5 and 25ºC within 90 days in simulated synthetic grape media and a standard grape marmalade formulation. Changes in active culture numbers, pH level, glucose concentration, and antioxidant properties were evaluated. Most of the isolates demonstrated higher growth in the grape marmalade than the synthetic grape marmalade, which was greater than 7 Log cfu/g within 90 days of storage at 5ºC. In addition, most of the wild isolates grew beyond the critical count of 106 cfu/g in sampling between 60 and 90 days of storage. Moreover, fermented grape marmalade with probiotics showed a strong antioxidant capacity that failed to differ significantly with the synthetic medium. The study confirmed L. paraplantarum, L. plantarum, W. paramesenteroides, and E. feacalis were ideal probiotics for fermentation process of grape marmalade.
ARTICLE | doi:10.20944/preprints201811.0170.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: CKD, ESKD, Death, anti-RAS, hyperkalemia, competing risk
Online: 7 November 2018 (14:48:30 CET)
Hyperkalemia burden in non-dialysis CKD under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalemia (sK≥5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of ESKD and death after visit 2. Age was 65±15 y, eGFR 35±17 mL/min/1.73 m2, proteinuria 0.40 (0.14-1.21) g/24h. In the two visits sK was 4.8±0.6 and levels ≥6 mEq/L were observed in 4%. Hyperkalemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis [sub-hazard ratio-sHR, 95%Confidence Interval-CI] evidenced that new onset [sHR 1.34, 95%CI 1.05-1.72] and persistent [sHR 1.27, 95%CI 1.02-1.58] hyperkalemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalemia status is common (37%) and predicts per se higher ESKD risk but not mortality.
REVIEW | doi:10.20944/preprints201806.0168.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: neovascular AMD; new therapies; anti-VEGFs; AMD signalling
Online: 12 June 2018 (06:26:56 CEST)
Neovascular age-related macular degeneration (nAMD) accounts for one of the leading causes of blindness among the aging population. The current treatment options for nAMD include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). However, standardised frequent administration of anti-VEGF injections only improves the vision in approximately 30%-40% of nAMD patients. Current therapies targeting nAMD pose a significant risk of retinal fibrosis and geographic atrophy (GA) development in nAMD patients. A need exists to develop new therapies to treat nAMD with effective and long-term anti-angiogenic effects. Recent research on nAMD has discovered novel therapeutic targets and angiogenic signalling mechanisms involved in its pathogenesis. For example, tissue factor, human intravenous immune globulin, interferon-β signalling, cyclooxygenase-2 (COX-2) and cytochrome P450 monooxygenase lipid metabolites have been identified as key players in the development of angiogenesis in AMD disease models. Furthermore, novel therapies such as NLRP3 inflammasome inhibition, targeted intraceptor nanoparticle therapy, inhibitors of integrins and tissue factor are currently being tested at the level of clinical trials to treat nAMD. The aim of this review is to discuss the scope for alternative therapies proposed to anti-VEGFs for the treatment of nAMD.
REVIEW | doi:10.20944/preprints201802.0084.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: dual anti platelet therapy; acute coronary syndrome; stents
Online: 12 February 2018 (05:13:18 CET)
Percutaneous coronary intervention(PCI) with stenting for the treatment of acute coronary syndrome(ACS) is the contemporary standard of care. Such treatment is followed by Dual anti-platelet therapy(DAPT) comprising of aspirin and a P2Y12 inhibitor. The efficacy of this therapy has been well established but the optimal duration of DAPT remains elusive, and has thus far attracted a prodigious deal of scientific attention. Decision regarding DAPT duration can be challenging clinically in the modern era with the evolution of newer stents, more potent antiplatelet agents and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. Major societal guidelines have emphasized comprehensive assessment of ischemic and bleeding risk, in turn recommending individualization of DAPT duration, thus encouraging "shared decision making". The following review is aimed at critically evaluating the available evidence to help make these crucial clinical decisions regarding duration of DAPT and triple therapy.
ARTICLE | doi:10.20944/preprints201608.0221.v1
Subject: Chemistry, Organic Chemistry Keywords: Tripterygium regelii; dimacrolide sesquiterpene pyridine alkaloids; anti-inflammation
Online: 29 August 2016 (10:46:49 CEST)
Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.
ARTICLE | doi:10.20944/preprints202105.0142.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Cancer Immunotherapy; Cancer Vaccine; Cancer Antigens; CRISPR-Cas9; Engineered T Cells.
Online: 7 May 2021 (11:10:13 CEST)
The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.
REVIEW | doi:10.20944/preprints202208.0163.v1
Subject: Medicine & Pharmacology, Urology Keywords: STAT3; prostate cancer; bladder cancer; upper tract urothelial carcinoma; renal cell carcinoma; penile cancer; testicular cancer
Online: 8 August 2022 (15:09:21 CEST)
Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.
ARTICLE | doi:10.20944/preprints202301.0489.v1
Subject: Life Sciences, Microbiology Keywords: multidrug resistance MDR; EPB (Xenorhabdus, (X. budapestensis, X. szentirmaii, X. innexii) and Photorhabdus) species); CFCM (cell-free conditioned media); NR-AMP (non-ribosomal-templated antimicrobial peptides); anti-microbial, (anti-bacterial, - anti-coccidial, -anti-protist, - activity; cytotoxicity; in vitro; in situ (local) bioavailablity; XENOFOOD; allometry
Online: 27 January 2023 (06:21:56 CET)
Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH),  cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD  which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).
REVIEW | doi:10.20944/preprints202202.0052.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cervical cancer; endometrial cancer; ovarian cancer; 2021 update; novel targeted therapies; immunotherapy
Online: 3 February 2022 (13:02:11 CET)
This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.
ARTICLE | doi:10.20944/preprints202007.0052.v1
Subject: Keywords: COVID-19; Breast Cancer; Breast Cancer (Suspected); Mammogram Images and Invasive Cancer
Online: 5 July 2020 (07:40:57 CEST)
Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.
REVIEW | doi:10.20944/preprints201911.0331.v1
Subject: Life Sciences, Biochemistry Keywords: pH and breast cancer; breast cancer etiology; breast cancer etiopathogenesis; breast cancer treatment; pH-centric anticancer paradigm; hydrogen ion dynamics of cancer; cancer proton reversal; MDR integral approach
Online: 27 November 2019 (04:57:00 CET)
Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.
REVIEW | doi:10.20944/preprints201707.0074.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cancer etiology; carcinogenesis; cancer prevention; stem cells; cancer stem cells; stem cell environment; cells of origin in cancer; somatic mutation theory of cancer
Online: 26 July 2017 (08:42:41 CEST)
All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.
ARTICLE | doi:10.20944/preprints202211.0176.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: prostate cancer; neuroendocrine prostate cancer; PET; DOTATATE
Online: 9 November 2022 (11:48:56 CET)
Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.
REVIEW | doi:10.20944/preprints202108.0208.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: lifestyle; esophageal cancer; cancer prevention; esophageal adenocarcinoma
Online: 9 August 2021 (18:05:44 CEST)
One of the most notable changes in the Esophageal Cancer (EC) epidemiology is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries, likely due to lifestyle and/or environmental factors that may play an important role in EAC onset. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations and EAC risk. A total of 106 publications met the inclusion criteria. Body mass index (BMI) and waist circumference (WC) are associated with increased EAC risk. Physical activity does not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a diet rich in animal fat, red meat, and processed meat. Alcohol does not seem to be related to EAC whereas smokers, particularly heavy smokers, have an increased risk of EAC. Primary prevention remains the best option to avert EAC. BMI and WC, along with low consumption of red and processed meat, high consumption of plant food, and the avoidance of smoking are pivotal for EAC prevention.
ARTICLE | doi:10.20944/preprints202107.0475.v1
Subject: Medicine & Pharmacology, Allergology Keywords: cancer pain; breakthrough cancer pain; cluster analysis
Online: 21 July 2021 (09:50:29 CEST)
Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting - Multicentric Survey (IOPS-MS) . A correlation analysis was performed to characterize NP-BTcP profile about its intensity, number of episodes per day, and type. The Multidimensional Correspondence Analysis (MCA) determined the identification of 4 groups (Phenotypes). A univariate analysis was performed to assess differences between the 4 Phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (Phenotype 1) to the worst (Phenotype 4). The univariate analysis found a significant association between the onset time >10 min in the Phenotype 1 (37.3%) vs. the onset ≤ 10 min in Phenotype 4 (74.2%) (p<0.001). The Phenotype 1 was characterized by gastrointestinal type of cancer (26.4%) respect to Phenotype 4 where the most frequent cancer affected the lung (28.8%) (p<0.001). Phenotype 4 was mainly managed with rapid onset opioids, while in Phenotype 1 many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p=0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. This strategy can provide many indications for identifying the diagnostic and therapeutic gaps on NP-BTcP management.
ARTICLE | doi:10.20944/preprints202106.0453.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Cancer-associated thrombosis; survey; anticoagulant; cancer patients
Online: 17 June 2021 (09:17:59 CEST)
Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess CAT knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind amongst patients/caregivers with CAT and identified significant gaps in patient awareness and knowledge of CAT. It also identified a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide healthcare professionals with awareness of what information should be shared with patients/caregivers as well as how and when that information should be provided. Notably, the importance of providing information on CAT risk and risk factors, how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to early identify CAT symptoms. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.