ARTICLE | doi:10.20944/preprints202103.0237.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: graphene oxide; human keratinocytes; proliferation; gene expression; cytotoxicity
Online: 8 March 2021 (16:20:37 CET)
Few-layer graphene oxide (GO) has shown none or very weak cytotoxicity and anti-proliferative effects in a wide range of cell lines such as glyoma cells and human skin HaCaT cells, in concentrations up to 100 µg/mL However, multi-layer GO has been hardly explored in the biomedical field. Thus, multi-layer GO was examined here in human keratinocyte HaCaT cells treated with different concentrations ranging from 0.01 to 150 µg/mL during different periods of times (3, 12 and 24 hours). The results of this study showed a time-concentration dependence with two non-cytotoxic concentrations (0.01 and 0.05 µg/mL) and a median effective concentration value of 4.087 µg/mL at 24 hours of GO exposure. Contrary to what has been reported for few-layer GO, cell proliferation of the HaCaT cells in contact with the multi-layer GO at 0.01 μg/mL showed identical proliferative activity compared to an epidermal growth factor (1.6-fold greater than the control group) after 96 hours. The effects of the multi-layer GO on the expression of 13 genes (SOD1, CAT, MMP1, TGFB1, GPX1, FN1, HAS2, LAMB1, LUM, CDH1, COL4A1, FBN and VCAN) at the non-cytotoxic concentrations of GO in the HaCaT cells were analyzed after 24 hours. Thus, the lowest non-cytotoxic GO concentration was able to up-regulate the CAT, TGFB1, FN1 and CDH1 genes, which confirms the great potential of multi-layer GO in the biomedical field.
REVIEW | doi:10.20944/preprints202103.0227.v1
Subject: Medicine And Pharmacology, Surgery Keywords: meshes; hernia; biomaterials; antimicrobials; surgery; abdominal wall
Online: 8 March 2021 (13:54:28 CET)
Worldwide, hernia repair represents one of the most frequent surgical procedures encompassing a global market valued at several billion dollars. This type of surgery usually requires the implantation of a mesh that needs the appropriate chemical, physical and biological properties for the type of repair. This review thus presents a description of the types of hernias, current hernia repair methods, and the state of the art of prosthetic meshes for hernia repair providing the most important meshes used in clinical practice by surgeons working in this area classified according to their biological or chemical nature, morphology and whether bioabsorbable or not. We emphasise the importance of surgical site infection in herniatology, how to deal with this microbial problem, and we go further into the future research lines on the production of advanced antimicrobial meshes to improve hernia repair and prevent microbial infections, including multidrug-resistant strains. A great deal of progress has been made in this biomedical field in the last decade. However, we are still far from an ideal antimicrobial mesh that can also provide excellent integration to the abdominal wall, mechanical performance, low visceral adhesion and minimal inflammatory or foreign body reactions, among many other problems.
COMMUNICATION | doi:10.20944/preprints202203.0035.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: calcium alginate; SARS-CoV-2; bacteriophage; phi 6; biomaterials; films; hydrogels
Online: 2 March 2022 (07:17:08 CET)
The current pandemic is urgently demanding to discover alternative materials capable of inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its negative charge density that may bind to viral envelopes inactivating membrane receptors.
ARTICLE | doi:10.20944/preprints202209.0333.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: rosé wine; probiotic yeast; fermentation; distillation; viability
Online: 22 September 2022 (05:44:56 CEST)
This paper reports for the first time on the production of probiotic alcoholic and non-alcoholic rosé wines with enhanced health benefits made with Saccharomyces cerevisiae var. boulardii probiotic yeast. The alcohol, sugar, volatile acidity lactic and malic acid contents were assessed for S. cerevisiae var. boulardii before and after fermentation and distillation and compared with a conventional Saccharomyces cerevisiae (ex-bayanus) yeast. The free amino nitrogen and gluconic acid concentrations in the musts were determined. Yeast viability was evaluated after fermentation and distillation as a function of time (0, 15 days, 3 months and 6 months) both at room temperature (25±0.5ºC) and refrigerator temperature (4±0.5ºC). The results obtained showed that the probiotic rosé wine produced with S. cerevisiae var. boulardii possesses the typical values and sensory attributes of other commercial wines produced with S. cerevisiae (ex-bayanus). The probiotic S. cerevisiae var. boulardii yeast survives the high alcohol content produced during fermentation and vacuum distillation. The study also showed that this probiotic rosé wine stored either at room temperature or in a refrigerator keeps its probiotic viability for at least six months, which makes it a promising for large-scale production, in which long storage times are required by both producers and consumers.
ARTICLE | doi:10.20944/preprints202108.0329.v1
Subject: Chemistry And Materials Science, Surfaces, Coatings And Films Keywords: face shield; facial protective equipment; SARS-CoV-2; phi 6; MRSA; MRSE; polyethylene terephthalate; benzalkonium chloride; COVID-19; multidrug-resistant bacteria
Online: 16 August 2021 (11:38:49 CEST)
Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.
COMMUNICATION | doi:10.20944/preprints202203.0185.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: SARS-CoV-2; COVID-19; variant; sublineage; transmission; immunity; infection; vaccination; non-pharmaceutical interventions
Online: 14 March 2022 (11:19:04 CET)
The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?
ARTICLE | doi:10.20944/preprints202107.0554.v1
Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; ORF10; Co-mutations; Intrinsic Protein Disorder; Ubiquitin Ligase Complex
Online: 26 July 2021 (09:07:38 CEST)
The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made fighting of the COVID-19 pandemic is a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in the lung tissues. Mutations and co-mutations in the emerging SARS-CoV-2 ORF10 variants are expected to impact the severity of the virus and its associated consequences. In this article, We highlight 128 single mutations and 35 co-mutations in the unique SARS-CoV-2 ORF10 variants in this article. The possible predicted effects of these mutations and co-mutations on the secondary structure of ORF10 variants and host protein interactomes are presented. The findings highlight the possible effects of mutations and co-mutations on the emerging 140 ORF10 unique variants from secondary structure and intrinsic protein disorder perspectives.
REVIEW | doi:10.20944/preprints202101.0297.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: COVID-19; SARS-CoV-2; carbon-based nanomaterials; antiviral properties; pneumonia
Online: 15 January 2021 (13:30:21 CET)
Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.
REVIEW | doi:10.20944/preprints202307.1595.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Glioblastoma, Notch signaling, lncRNAs, miRNAs
Online: 24 July 2023 (10:51:59 CEST)
Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.
ARTICLE | doi:10.20944/preprints202106.0472.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; Mutations; Furin Cleavage Site (FCS); Evenly-uneven; Invariant regions
Online: 18 June 2021 (09:22:08 CEST)
Several hypotheses have been presented on the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from its identification as the agent causing the current coronavirus disease 19 (COVID-19) pandemic. So far, no hypothesis has managed to identify the origin, and the issue has resurfaced. Here we have unfolded a pattern of distribution of several mutations in the SARS-CoV-2 proteins across different continents comprising 24 geo-locations. The results showed an evenly uneven distribution of unique protein variants, distinct mutations, unique frequency of common conserved residues, and mutational residues across the 24 geo-locations. Furthermore, ample mutations were identified in the evolutionarily conserved invariant regions in the SARS-CoV-2 proteins across almost all geo-locations we have considered. This pattern of mutations potentially breaches the law of evolutionary conserved functional units of the beta-coronavirus genus. These mutations may lead to several novel SARS-CoV-2 variants with a high degree of transmissibility and virulence. A thorough investigation on the origin and characteristics of SARS-CoV-2 needs to be conducted in the interest of science and to be prepared to meet the challenges of potential future pandemics.