The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH). Haematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves. In a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a perspective multitarget drug candidate for treatment of Alzheimer’s disease.

Piceatannol is a naturally occurring polyphenolic compound that is widely found in grapes, blueberries, mushrooms, passion fruit and other edible fruits and vegetables. It has a variety of biological activities and pharmacological effects, including anti-inflammatory, antioxidation, antiaging, antiviral, antitumor, anticancer, antiatherosclerosis, antiparasitic, immunoregulatory, and cardiovascular protection effects. The aim of this study was to investigate the antiherpesvirus effects of piceatannol. Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiherpesvirus effect of piceatannol. In this study, we evaluated the antiviral activity of piceatannol against PRV in vitro and in vivo. The results showed that piceatannol could reatrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, the IC50 was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. The addition of piceatannol at different stages of PRV infection inhibited the viral adsorption and intracellular replication phases of PRV. Piceatannol significantly reduced the expression levels of the IE180, EP0, UL29, UL44, US6 and UL27 genes of PRV within 48 h, significantly reduced the expression levels of the PRV gB and gD proteins, and reduced PRV-induced apoptosis. Molecular docking showed that piceatannol had good binding activity with the PRV gB and gD proteins. The results of animal experiments in vitro indicated that piceatannol could delay the onset of disease, improve the survival rate of the mice (14.3%), reduce the viral load in the brain and kidney of the mice, alleviate the pathological changes in the mouse tissues and organs, and increase the levels of TNF-α, IEN-γ and IL-4 in the serum of the mice. These data indicate that piceatannol has good anti-PRV activity in vitro and in vivo, indicating that it could be a novel antiherpesvirus infection agent in the future.

Diabetes mellitus is a global health issue that necessitates the development of novel therapeutic approaches. Today numerous experimental methods have been used and set up to evaluate novel drugs with antidiabetic effects. In addition, several research studies have been done to induce diabetes under in vitro and in vivo conditions, but only a small number of these efforts are currently in a usable stage. This review aims to provide useful guidance for researchers who seek to evaluate the antidiabetic potential of drugs, agents, or new medications using the standard methods published by authorities and academics worldwide organizations and research centers. In this review, we collected 132 relevant articles from prominent databases such as PubMed, ScienceDirect, Scopus and others to summarize in vitro and in vivo experimental validation of antidiabetic treatment from 1943 to present.

Background: The identification of novel therapeutic strategies for Ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-Hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with cyste-ine-dependent deubiquitinating enzymes (DUBs), thus affecting the ubiquitin-proteasome de-pendent degradation of proteins. Methods: 2c phenotypic/molecular effects were studied in two OC cell lines, primary tumor cells cultured in 2D/3D and in a mouse xenograft model. We also propose an in-silico model of 2c interaction with DUBs. Finally, we tested the effect of 2c conju-gated to several linkers to generate 2c-derivatives usable for improved drug delivery. Results: 2c effectively impairs OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs pro-teasome activity and triggers apoptosis most likely by interacting with DUBs; we propose a mechanism for the interaction with a model DUB via an in-silico evaluation of the en-zyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcrip-tion factor E2F1. Finally, 2c activity is often retained after the conjugation with linkers. Conclu-sion: Our data strongly support the potential therapeutic value of 2c/derivatives in OC.

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 µM were not significant difference (p > 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p < 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

Nociceptive innervation of the thoracolumbar fascia (TLF) has been investigated over decades, however these studies have not been compiled or collectively appraised. The purpose of this scoping review was to assess current knowledge regarding nociceptive innervation of the TLF to better inform future mechanistic and clinical TLF research targeting low back pain (LBP) treatment. PubMed, ScienceDirect, Cochrane and Embase databases were searched in January 2021 using relevant descriptors encompassing fascia and pain. Eligible studies were: (a) published in English; (b) preclinical and clinical (in vivo and ex vivo) studies; (c) original data; (d) included quantification of at least one TLF nociceptive component. Two-phase screening procedures were conducted by a pair of independent reviewers, data were extracted and summarized from eligible studies. The search resulted in 257 articles of which 10 met inclusion criteria. Studies showed histological evidence of nociceptive nerve fibers terminating in low back fascia, suggesting a TLF contribution to LBP. Noxious chemical injection or electrical stimulation into fascia resulted in longer pain duration and higher pain intensities than injections into subcutaneous tissue or muscle. Pre-clinical and clinical research provides histological and functional evidence of nociceptive innervation of TLF. Greater knowledge of fascial neurological components could impact LBP treatment.

Ceratonia siliqua L. is a medicinal plant that has long been used in traditional Moroccan medicine to treat many diseases. This study aimed to assess the impact of the stages of the immature phase of carob pulp (M1, M2, M3, M4, and M5) on phytochemical composition, antioxidant activity, and antidiabetic activity of Ceratonia siliqua L. The identification of the phenolic profile by HPLC-UV/MS-MS and the study of the antidiabetic effect by in silico, in vitro, and in vivo studies were carried out for extracts with a high content of phenolic compounds from immature wild carob pulp from the communes of Timoulit (TM), Bin Elouidane (AW), and Ouaouizerth (TG) in the province of Azilal in the Beni Mellal-Khenifra region. The results revealed a gradual increase in total sugar content over the pulp's ripening period, reaching a value of 2134 ±56.23 mg GE/100 g fresh matter (FM) for TG. The three locations showed peak values for total polyphenol content (TPC), total flavonoid content (TFC), and total condensed tannin (TCT) at the M2 stage. AW has the highest concentrations of TPC (3819 ± 226.4 mg GAE/100 g FM), TFC (1034 ± 57.08 mg QE/100 g FM), and TCT (1472 ± 28.46 mg CE/100 g FM). The DPPH assay (7892 ± 296.1 mg TE/100 g FM) and the FRAP assay (278.2 ± 7.85 mg TE/100 g FM) both demonstrate that the TG zone is a highly potent antioxidant zone. In contrast, the AW site exhibits a markedly elevated value of 725.4 ± 103.6 mg TE/100 g FM in the ABTS assay. HPLC-UV-MS/MS analysis showed that the methanolic extracts of immature carob pulp (MEICP) from the three areas contained several different chemical compounds. The most prevalent were 3-O-p-coumaroyl-5-O-caffeoylquinic acid, quercetin 3-methyl ether, gallic acid, and galloylquinic acid. Immature carob pulp extract. (ICPE) from AW showed the strongest in vitro inhibition of pancreatic α-amylase (IC50 = 0.405 µg/mL) and TG extracts were most potent against intestinal α-glucosidase (IC50 = 0.063 µg/mL). In vivo, AW, TG, and TM extracts significantly reduced postprandial glycemia in rats, with AW having the greatest effect. These results highlight the antidiabetic potential of ICPE. The 3-O-p-Coumaroyl-5-O-caffeoylquinic acid showed a better affinity for α-amylase compared to acarbose and interacted significantly with several amino acid residues of the enzyme. Similarly, this molecule and 3,4-Dicaffeoylquinic acid demonstrated a strong affinity for α-glucosidase, suggesting their potential as natural inhibitors of enzymes involved in carbohydrate metabolism. Most of the compounds are not substrates of P-glycoprotein and exhibit high intestinal absorption. Furthermore, the majority of these compounds do not act as inhibitors or substrates of CYP450 enzymes, reinforcing their suitability for development as oral medications. These results underscore the potential of immature carob pulp as a promising antidiabetic agent.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

Using polymethylmethacrylate (PMMA) bone cement is widespread in orthopedic surgeries for implant fixation and as a carrier for antibiotic delivery to prevent and treat infections. This review comprehensively evaluates in vitro studies investigating the antibiotic elution profiles and mechanical properties of PMMA bone cement. We explore the kinetics of antibiotic release, factors influencing elution efficiency, and the impact of various antibiotics on the mechanical properties of PMMA composites. At the same time, we examine how the inclusion of antibiotics affects the mechanical integrity of PMMA, including parameters such as compressive strength, tensile strength, and fatigue resistance. Through a detailed analysis of these studies, this review aims to provide insights into optimizing PMMA bone cement formulations for enhanced therapeutic efficacy and structural performance.

Hepatocellular carcinoma (HCC) results in high mortality due to ineffective systemic therapy. Human immortalized cell lines are commonly used to study anti-tumour effects in the context of new anti-tumour therapies and tumour biology. As immortalized cell lines have limited biological relevance and heterogeneity compared to primary cells, patient-derived tumour tissues and corresponding immune cells are the gold standards for studying the complexity of individual tumour entities. However, culturing primary HCC cells has a low success rate. Here, we aimed to establish a reproducible approach to preserve the patient-derived liver cancer cells for in vitro and in vivo studies. The underlying study aimed to establish an in vitro pre-screening platform to test treatment options' effectivity and dosage, e.g., for new substances, autologous modified immune cells, or combined therapies in HCC. We initially employed 15 surgical resection specimens from patients with different HCC entities for isolation and preservation. The isolated liver cancer cells from four HCC-diagnosed patients were used for orthotopic transplantation into the healthy liver of immunodeficient mice, allowing them to grow for six months before human liver cancer cells were isolated and cultured. As a result, we generated and characterized four new primary-like liver cancer cell lines. Compared to immortalized HCC cell lines, freshly generated liver cancer cells displayed individual morphologies and heterogenous protein-level characteristics. We assessed their ability to proliferate, migrate, form spheroids, and react to common medications compared to immortalized HCC cell lines. All four liver cancer cell lines exhibit strong migration and colony-forming characteristics in vitro, comparable to extensively investigated immortalized HCC cell lines. Moreover, the four etiological different liver cancer cell lines displayed differences in the response to 5-FU, Sorafenib, Axitinib and Interferon-alpha treatment, ranking from non-responders to responders depending on the applicated medication. In sum, we generated individual patient-derived liver cancer cell lines suitable for predictive in vitro drug screenings and moreover for xenograft transplantations to realize the in vivo investigation of drug candidates. We overcame the low cultivation success rate of liver cancer cells derived from patients and analyzed their potential to serve a pre-clinical model.

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. Aureus and K. Pneumoniae. The compounds CY-R2-25 and CY-R2-28 have been identified as the high potential molecules in this series based on in vitro experiments. CY-R2-25 has zone of inhibition values of 15 0.82 and 14 0.7, whilst CY-R2-28 has the zone of inhibition values of 18 0.95 and 16 0.82 against S. Aureus and K. Pneumoniae, respectively. MIC and MIB values for CY-R2-25 and CY-R2-28 against S. Aureus and K. Pneumoniae are 0.25 and 0.5, respectively.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments many times lacking efficiency and leading to severe side-effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150.4 ± 3.7 nm) and homogeneous (PDI of 0.162 ± 0.008) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models, with GI50 values between 12.37 ng/mL and 14.72 ng/mL. Additionally, they also revealed substantial anti-inflammatory activity, with an IC50 of 28.98 ng/mL, effects that have been reported to be complementary to direct antitumor activity. Finally, the niosomes' safety was assessed, both in vitro, on skin, liver and kidney cells, and ex vivo, in a HET-CAM assay, and results showed that compound encapsulation increased its safety. Hence, small and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies.

In this study, hybrid materials were synthesized incorporating curcumin, Cu²⁺ or Fe³⁺, and Kappa-carrageenan as a reducing agent to improve its stability, considering that curcumin has low thermal and solution stability, which limits its applications. Colorimetric analysis showed color changes in the hybrids, ultraviolet-visible spectroscopy revealed band shifts in the hybrids, and infrared analysis indicated shifts in wavenumbers, suggesting changes in the vibrational state of curcumin after bonding with metal ions. These techniques confirmed the formation of the hybrid materials. Thermogravimetric and chromatographic analyses demonstrated greater thermal and solution stability for the hybrids compared to curcumin. Additionally, the hybrid composites effectively developed natural and sebaceous latent fingerprints with good clarity and contrast on glass surfaces. Both composites performed similarly to commercial gold powder. When applied to surfaces representative of forensic scenarios, the composites were versatile, revealing sufficient fingerprint details for human identification on both porous and non-porous surfaces. Scanning electron microscopy images showed greater clarity in sebaceous and natural fingerprints developed with the Fe composite compared to the Cu composite, due to minimal interaction of Fe with the glass surface.

Despite extensive research on autism in children, much less attention has been given to the transition into adulthood. This study aims to address this gap by examining the dietary behaviors of young adults with autism during this critical transition period, highlighting the role of diet in enhancing their readiness for adulthood. Forty-seven participants (mean age 21.0 ± 1.1 years), both male and female, were involved in this study. Participants had various comorbidities, such as mood disorders, attention-deficit/hyperactivity disorder, depression, and anxiety disorders, for which they required medication. Dietary behavior was assessed using the Starting the Conversation: Diet survey, while transition readiness was measured with the Transition Readiness Sur-vey. T-test and regression analysis were utilized to evaluate the data. The results indicated that participants did not follow healthy eating habits, as reflected by the dietary scores (1.08 ± 0.07), and were not adequately prepared for adulthood, as shown by the transition readiness scores (3.19 ± 1.10). A statistically significant and negative correlation was found between dietary pat-terns and transition readiness (r = -0.51, p < 0.001), indicating an adverse relationship: transition readiness ratings decline as diet scores rise. Linear regression analysis revealed that dietary habits accounted for 26.20% of the variation in transition readiness, with the confidence interval for the coefficient of dietary habits being -2.89 to -0.95 (p = 0.002). The negative significant correlation between dietary scores and transition readiness scores shows that diet behavior significantly influences participants’ assessed readiness for transition.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

Background/Objective: In-vivo diabetes detection of glucose were sought using square-wave anodic stripping voltammetry (SW), with bismuth-immobilized carbon nanotube paste electrode (BCE). Methods: The optimum analytical results indicated sensitive peak signals on the BCE. The raw voltammogram was approached within the 1 mgL^-1-14 mgL^-1 and 10 ugL^-1-140 ugL^-1, detection limits with preconcentration times of 100 and 200 sec. Results: The relative standard deviation was 0.02 % (n = 15) of 10.0 mgL^-1 under optimum conditions. The analytical detection limit (S/N) was attained at 8 ugL^-1. The handmade microsensor was directly used in vivo on the living fish brain and human urine.Conclusion: The method was applied at real time in vivo, without requiring any pretreatment and other ionic electrolyte solutions. It can be used for medicinal and other materials requiring biological-fluid detection in real time. This study was designed to be suitable for real-time unmanned remote diagnosis and therapeutic drug injection into the body, micro-needle long-term administration, wearable artificial skin tattoo sensor, and real-time control. In addition, the glasses monitor was designed to be suitable for multitasking and multi-user control.

Cruciferous vegetables represent a valuable source of bioactive compounds. However, there is currently a paucity of information regarding the extent to which these compounds remain bioavailable to the body following thermal treatment and digestion processes within the digestive tract. Accordingly, the aim of this study was to evaluate the impact of heat treatment and in vitro digestion on the level of selected bioactive compounds in Brussels sprouts. The Brussels sprouts samples were subjected to a range of thermal processing techniques, which were then followed by a simulated in vitro digestion. The investigated compounds were analysed using UV-Vis spectrometry and liquid chromatography coupled to mass spectrometry (LC-MS). The findings revealed that the sous-vide method of cooking Brussels sprouts resulted in significantly higher losses of glucosinolates (GLS) in comparison to conventional cooking methods. No significant differences were observed with regard to isothiocyanates and indoles. The analysis of GLS following digestion revealed that the process was more effective after sous vide and traditional cooking, and slightly less effective after steam cooking. With regard to individual compounds, glucoraphanin (GRA), glucoraphenin (GIV) and gluconasturtiin (GNS) were found to be completely degraded, whereas methoxyglucobrassicin (metGBS) was the most resistant to digestion in both the sous vide and steamed Brussels sprouts. The results indicated that the process of simulating digestion had no significant effect on isothiocyanates and indoles. This suggests that, if present in the heat-treated samples, these compounds remained stable during the in vitro digestion procedure.

The numerous biological activities of phenothiazine and sulphonamide derivatives, especially their antibacterial qualities, have attracted so much interest. In this study, the synthesis and characterization of phenothiazine-3-sulphonamide derivatives and evaluation their antimicrobial activity against the following pathogenic microorganisms is reported. Two gram-positive bacteria; (Staphylococcus aureus, and Streptococcus pyogenes), two gram-negative bacteria; (Escherichia coli, and Salmonella typhi) as well as one fungus (Aspergillus fumigatus) were used while ciprofloxacin, gentamycin and ketoconazole served as standard drugs. The synthesis of the derivatives was achieved through a base catalyzed the reaction of 4-chloroaniline with 1-naphthylamine to form 1-(naphthalen-1-yl) benzene-1,4-diamine. This intermediate was then treated with sulphur and iodine to yield the phenothiazine derivative while subsequent treatment of the phenothiazine compound with sulphonyl chlorides gave the final products. The synthesized compounds were characterized via proton nuclear magnetic resonance (1HNMR), carbon-13 nuclear magnetic resonance (13C NMR) and Fourier-transform infrared (FTIR) spectroscopic techniques. The minimum inhibitory concentration (MIC) of each compound was then determined using the agar well diffusion method. To predict the binding energies and patterns of the synthesized compounds with target proteins of the above mentioned microorganisms, molecular docking simulations were run using Autodock Vina software (version 4.2). The spectra data of the compounds for FTIR, 1H NMR and 13C NMR (δ) spectral data were consistent with the assigned structures of the synthesized compounds. The binding energies (kcal/mol) for in silico antimicrobial studies were in the range -5.1 to -7.6 kcal/mol. The MIC values were in the range -3.5 to 1.0 mg/L. The results of the in vitro test revealed that the synthesized compounds exhibits promising antimicrobial activity, and showed excellent bactericidal and fungicidal activities. The results obtained showed that the synthesized compounds possess drug-like properties and are good starting materials for drug production.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

This literature review was aimed to collect investigations on the in vivo evidences for bacteria associated to fermented dairy foods to behave as probiotics with beneficial effects in the prevention and treatment of various diseases. All main bacterial groups commonly present in high numbers in fermented milks or cheeses were taken into account, namely starter lactic acid bacteria (SLAB) Lactobacillus delbrueckii subsp. bulgaricus and lactis, L. helveticus, Lactococcus lactis, Strepto-coccus thermophilus, non starter LAB (NSLAB) Lacticaseibacillus spp., Lactiplantibacillus plantarum, dairy propionibacteria and other less frequently encountered species. Only studies regarding strains of proven dairy origin were considered. Studies in animal models and clinical studies showed that dairy bacteria ameliorate symptoms of inflammatory bowel disease (IBD), mucositis, metabolic syndrome, aging and oxidative stress, cancer, bone diseases, atopic dermatitis, allergies, infections and damages caused by pollutants, mild stress and depression. Immunomodulation and changes in the intestinal microbiota were the mechanisms most often involved in the observed effects. The results of the studies considered indicated that milk and dairy products are a rich source of beneficial bacteria that should be further exploited to the advantage of human and animal health.

Recently, the concept of participatory democracy developed in the early 1970s has come back into fashion to revitalize the public involvement in political decision-making processes. Public par-ticipation in forest policy has been fully conceptualized by the scientific community in the late 1990s and early 2000s, but in many contexts the practical application remains unfulfilled. The aim of this study is to identify and analyze the participatory techniques used in literature to increase knowledge and facilitate its transferability into forest policies and strategies. A literature review was carried out to offer an overview of the participatory techniques adopted in the deci-sion-making process. At the end of literature review, 25 participatory techniques were identified based on over 2,000 publications. Afterwards, the participatory techniques were assessed using seven indicators (degree of participation, type and number of participants, time scale, cost, po-tential influence on policy). The results showed that the type of actors involved in the participa-tory technique is a key variable for the complexity and usefulness of the process, while the number of participants influences how information is disseminated. The Principal Component Analysis highlighted that the participatory techniques can be divided in three groups: the first group includes those techniques with a high degree of participation and a contextual high po-tential influence on policies, the second one includes techniques with a costs in terms of re-sources, while the third one consists of those with a large number of participants and reduced time requirements.

Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

Silicon nanoparticles (SiNPs) are highly promising for biological and biomedical applications, including bioimaging, due to their unique opltical properties (i.e. strong fluorescence and very high photostability). Their low or negligible in vitro toxicity has been reported, but in vivo toxicity and biological effects of SiNPs are still uncertain. Uncoated SiNPs were dispersed in distilled water via sonication, and their rapid aggregation was observed (319.0 ± 2.4 nm particle size). In vivo toxicity was studied using Danio rerio embryos and larvae. Rapid aggregation in their incubation medium was observed; besides that, SiNPs at 25 mg/L or higher concentration induced swim bladder malformation and/or death of the fish. The estimated LC50 value for 7-day larvae was 180 mg/L. This is the first in vivo toxicity study of uncoated and unfunctionalized SiNPs. To achieve better stability in biological media and lower toxicity, SiNPs should be covered with hydrophilic layers, but their absorption by cellular membranes may be weaker in this case.

Infections due to Candida spp., they are a threat to global health, with high rates of morbidity and mortality due to their drug resistance, especially in immunocompromised people. Thus, the search for new alternatives is urgent today. In recent years, combined therapy with compounds of natural origin has been proposed as an alternative. Considering the biological potential of isoespintanol (ISO) and continuing with its study, the objective of this research was to assess the effect of ISO in combination with the antifungals, fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP), against clinical isolates of C. tropicalis and evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84), in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. Evaluation of the mice by direct vision showed no behavioral changes or variation in weight during treatment; furthermore, the analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process and histopathological studies of lung, liver and kidney showed no signs of toxicity caused by ISO; this was consistent with the analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated. Our results place ISO as a monoterpene of interest in the search for compounds with pharmacological potential.

During the preclinical research process, multiple factors can be difficult to implement without the careful consideration and planning of each step. As research has become more advanced with the use of increasingly complex technology, animal models have also become essential for understanding the potential impact of devices, drug therapies, and surgical techniques on humans before clinical trials are conducted. The use of an in vivo animal model is a key and necessary step in the progression of preclinical research studies that will lead to future medical inventions and innovation. Here, we describe the three phases of effectively designing a preclinical research protocol: the research, preprocedural planning, and experimental phases. Furthermore, we provide researchers with guidance through these phases and discuss important considerations.

Abstract: To obtain bovine oocytes in high quality, effects of vitamin C (VC) on in vitro maturation (IVM) of bovine oocytes and early embryo development were investigated. The results showed that: 1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate, while no effects on the development of parthenogenetic embryos; 2) The in vitro culture (IVC) medium containing 20 µg/mL VC increased the cleavage rate of the in vitro fertilized (IVF) embryos, enhanced the mRNA levels of pluripotency gene Oct4, Sox2, Cdx2 and Nanog in the blastocysts, but no effect on the blastocyst rate; 3) Combing supplemention of 50 µg/mL in IVM medium + 20 µg/ml VC in IVC medium (VC 50/20) increased the cleavage rate of IVF embryos and enhanced the mRNA levels of Oct4, Sox2, Cdx2 and Nanog in the blastocysts; 4) Combination of VC 0/20 and VC 50/20 enhanced the expression of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the expression of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and decreased the Bcl-2/Bax ratio in blastocysts. Together, VC supplementation at tuned concentration as well its combination in IVM and IVC media improves the developmental rates of bovine oocytes and embryos.

Among the alternatives pointed out as able to make livestock a more efficient activity and reduce its environmental impact, the use of feeds with high digestibility and the use of non-conventional fodder species can be highlighted. Tithonia diversifolia (Hemsl.) A. Gray (TD) has already gained attention as a feed for ruminants. Nonetheless, there has been little discussion about the impacts of this plant on the rumen dynamics that lead to better animal performance. The aim of this study was to assess how increasing levels of TD could affect ruminal microbial biomass synthesis, degradability, and in vitro gas production (IVGP) of diets. Four diets were evaluated: a control diet (TD0: 400 g kg-1 soybean meal and corn grain, and 600 g kg-1 Tifton 85 hay (Cynodon spp)) and three increasing levels of TD (TD9: 90, TD27: 270, and TD45: 450 g kg-1 – dry matter basis) as a replacement for dietary roughage. A 96-hour IVGP assay was carried out and five incubation times (2, 4, 10, 24, and 96 hours) were used for degradability determination. Gas produced, methane (CH4), degradability of organic matter (IVDOM), short-chained fatty acid (SCFA) production, partitioning factor (PF), and microbial biomass (MB) were evaluated among treatments. There was no significant effect (P&gt;0.05) between TD inclusion and IVGP at most incubation times; only at 6 hours of incubation did gas production increase linearly with TD inclusion (R2=0.19; P&lt;0.05). TD inclusion had no effects on CH4. IVDOM increased linearly with TD inclusion at 6 and 10 hours, with TD45 being more degradable than the control diet at 6 hours only. There was a positive linear relationship (R2=0.20; P&lt;0.05) between TD inclusion and PF. TD45 had significantly higher PF values than the control. MB also increased linearly (R2=0.30; P&lt;0.05) with TD inclusion, and all diets with TD had significantly more MB than the control diet. The inclusion of TD at the levels used in this work was revealed to have a positive impact on microbial protein synthesis, which could be related to the higher microbial efficiency of increased substrate quality.

During embryo development, the endoplasmic reticulum (ER) acts as an important site for protein biosynthesis, however, in vitro culture (IVC) can negatively affect ER homeostasis. Thereby, the aim of our study was to evaluate the effects of supplementation of tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, in the IVC of bovine embryos. Two experiments were carried out: Exp. 1: evaluation of blastocyst rate, hatching kinetics and gene expression of hatched embryos after being treated with different concentrations of TUDCA (50, 200 or 1,000 μM) in the IVC; Exp. 2: evaluation of the re-expansion, hatching, and gene expression of hatched embryos previously treated with 200 µM of TUDCA at IVC and submitted to vitrification. There was no increase in the blastocyst and hatched blastocyst rates treated with TUDCA in the IVC. However, embryos submitted to vitrification after treatment with 200 µM of TUDCA, increased hatching rate post-warming, together with a down-regulation in the expression of ER stress-related genes and the accumulation of lipids. In conclusion, this work showed that the addition of TUDCA during in vitro culture can improve the cryotolerance of the bovine blastocyst through the putative modulation of ER and oxidative stress.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Acacia nubica is well-adapted to harsh conditions and offers valued socio-economic and environmental benefits. This research studied seed germination and seedling growth of A. nubica in vitro in response to the application of different concentrations of sodium hypochlorite, sucrose, and Murashige and Skoog (MS) medium. The synchrony, percentage, and rate of germination of A. nubica seed were studied. Seedling development was assessed by measuring the shoot, root, and number of nodes. Sodium hypochlorite at 10% produced the maximum germination percentage, while 5% induced a faster and more uniform emergence. Sucrose has various effects on seed emergence and germination depending on the concentrations; 30 g/L elicited the highest germination, while 10 g/L improved seed emergence rate with higher uniformity. The highest seed germination was achieved on ¼-MS medium, although 0-MS strength recorded faster and more synchronized germination. The development of A. nubica seedlings was influenced by MS medium strengths and sucrose concentrations. Full MS medium produced the highest shoot length and the highest vigor index with the addition of 20 g/L sucrose and the maximum root length with 50 g/L sucrose. Also, 30 g/L sucrose gave the maximum number of nodes and the maximum root/shoot ratio. However, ½-MS strength yields the highest seedling biomass with 30 g/L sucrose. This is the first successful report on the seed germination and seedling growth of A. nubica in vitro.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

Prediabetes is a significant risk factor for the development of Type 2 diabetes, cardiovascular diseases, chronic kidney disease, and other complications. Early diagnosis of prediabetes, coupled with education on lifestyle changes that support blood glucose management, are crucial for the prevention or delay of type 2 diabetes and related complications. This study aimed to examine the effects of individualized nutrition therapy (INT) combined with continuous glucose monitoring (CGM) on blood glucose control in individuals with prediabetes who are overweight or obesese. Participants (mean age ± SD: 55 ± 6 years; BMI: 31.1 ± 4.1 kg/m²) were randomly assigned to either the treatment group (n = 15) or the control group (n = 15). Both groups received INT and CGM, but the control group was blinded to the CGM data until the end of the study. Participants were followed for 30 days and visited the lab every 10 days for CGM replacement, study measurements, and dietary consultations. The treatment group showed a significant increase in the percent of time in the target blood glucose range (p=0.02) and a significant decrease in mean blood glucose concentration (p&lt;0.05), glucose management indicator (p=0.02), percent coefficient of variation for blood glucose (p=0.01), and the percent time spent in the high or very high blood glucose ranges (p= 0.04). These changes were not statistically significant for the control group. We conclude that adding CGM feedback to INT resulted in better management of blood glucose levels in overweight or obese individuals with prediabetes.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

Regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new hints on microglia heterogeneity across central nervous system (CNS) regions are still being unraveled by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on in vitro behavior by applying the same experimental protocol and culture conditions. We analyzed microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in spinal cord-derived glial cultures, presenting different expression of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-. Morphologically, cortical microglial cells are more complex and present longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired in the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.

Microparticles derived from biomaterials are becoming increasingly popular for various applications, particularly in drug delivery systems. In this study, the water-in-oil (W/O) emulsification-diffusion method was used to create cellulose (C), silk fibroin (SF), and C/SF composite microparticles. We then observed the morphology of all obtained microparticles using scanning electron microscopy (SEM), evaluated their functional groups using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and conducted thermogravimetric analysis using a thermogravimetric analyzer (TGA). SEM micrographs indicated that the native SF microparticles have the highest spherical shape with smooth surfaces. With blue dextran, the C microparticle was smaller compared to the native microparticle, while the drug-loaded SF microparticles were bigger than the native microparticle. The morphological surfaces of the C/SF composite microparticles were varied in shape and surface depending on the C/SF ratio used. The spherical shape of the C/SF composite microparticle was increased as SF content increased. Furthermore, the size of drug-loaded C/SF composite microparticles was gradually increased by the SF content. The significant functional groups in the C and SF structures were identified based on the ATR-FTIR data, and a suggestion was made regarding the interaction between the functional groups of each polymer. When compared to both native polymers, the C/SF composite microparticles exhibit improved thermal stability. The C/SF composite microparticle at a 1:3 ratio had the lowest drug release content, whereas the hydrophilicity of the C microparticle affected the highest drug release content. As a result, one crucial factor affecting the medication released from the microparticle is its thermal stability. According to the obtained results, C, SF, and C/SF composite microparticles show promise as delivery systems for drugs with controlled release.

Introduction: Pharmaceutical tablets are solid forms administrated orally and they constitute 80% of the market because of its best stability and ease of large-scale production, adherence and treatment. The Brazilian Legislation establishes that for a drug to be registered as a similar or generic drug is necessary to verify the pharmaceutical equivalence in relation to the reference drug, indicated by ANVISA, through quality control tests, ensuring that the drug is approved with satisfactory quality. Objective: to evaluate the reference, generic and similar glibenclamide tablets through quality control tests, comparing the results with each other and relate clinical impacts on the patient in the face of changes in the quality control of medicines. Methodology: tests of average weight, friability and disintegration were done, according to the Brazilian Pharmacopoeia VI Edition, in uncoated tablets of Glibenclamide 5mg Reference (Daonil), Generic (Glibenclamide) and Similar (Glionil), and the results obtained were compared with the that advocates the scientific literature. Results: Data referring to the average weight: Reference 0.1591g, Generic 0.1002g and Similar 0.0996g; For friability: Reference value 0.54%, Generic value 0.49% and Similar value 0.28%. The disintegration tests showed the following times: Reference 35 seconds, Generic 29 seconds and Similar 33 seconds. Conclusion: the tests to which the glibenclamide tablets were submitted showed results within the parameters established by the Brazilian Pharmacopoeia.

Ice formation on aircraft surfaces poses significant safety risks, and current detection systems often struggle to provide accurate, real-time predictions. This paper presents the development and comprehensive evaluation of a smart ice control system using a suite of machine learning models. The system utilizes various sensors to detect temperature anomalies and signal potential ice formation. We trained and tested supervised learning models (Logistic Regression, Support Vector Machine, Random Forest), unsupervised learning models (K-means clustering), and neural networks (Multi-Layer Perceptron) to predict and identify ice formation patterns. Experimental results demonstrate that our smart system, driven by machine learning, accurately predicts ice formation in real-time, optimizes de-icing processes, and enhances safety while reducing power consumption. This solution holds the potential for improving ice detection accuracy in aviation and other critical industries requiring robust predictive maintenance.

Wheat pollen, characterized by its short lifespan, exhibits rapid germination after anthesis. The preservation of wheat pollen is contingent upon environmental factors, including temperature, relative humidity, light, and wind. The objective is to develop a method for preserving wheat pollen effectively, specifically for the purpose of breeding. The short longevity of wheat pollen grains renders it impractical to conduct tests for pollen viability and in vitro germination on a large scale. Herein, the impact of storage temperatures and duration was assessed on pollen viability and in vitro germination to optimize storage conditions for preserving pollen viability. Pollen grains from 50 diverse spring wheat genotypes, each with three replicates, were harvested and stored at temperatures of 22°C, -20°C, and 4°C. Subsequently, pollen viability and in vitro germination rates were determined after storage of 1, 3, and 6 days. The results revealed that storage temperatures, durations, genotypes, and their interactions had a statistically significant impact on both pollen viability and in vitro germination. Notably, when pollen was kept at 22°C, almost all genotypes exhibited a loss of pollen viability and in vitro germination after 1, 3, and 6 days of storage. Likewise, storage at -20°C failed to extend pollen germination. However, at a storage temperature of 4°C, the pollen of 36 wheat genotypes exhibited a range of 6-14% in vitro pollen germination and remained viable even for 6 days. Simple linear regression analysis further revealed a significant negative correlation between pollen viability, in vitro germination, and storage time and temperature. In conclusion, our findings underscore 4°C as the optimal temperature for preserving pollen viability and in vitro pollen germination in spring wheat for up to 6 days. The results of the present study suggests that pollen viability of wheat is genotype de-pendent, storage temperature and storage duration. Thus, the 36 wheat genotypes identified during the present work could be efficiently maintained at 4◦C for short-term storage (6 days) and could be further used for genetics and breeding purposes.

The main purpose of our research is the evaluation of the efficacity of solvent polarity on phenolic composition, as well as the antibacterial, and antioxidant activities of extract of Moroccan Mentha aquatica L., leaves. To attempt these objectives, the HPLC-DAD was used to identify the biomolecules. The total amount of phenolic and flavonoid content was determined using the Folin-Ciocalteu and aluminum trichloride processes as well as the DPPH, RP, and TAC tests were used to evaluate the antioxidant capabilities. In addition, by employing both in vitro and in silico analysis through the microdilution method, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extracts were assessed against multidrug-resistant bacteria. Furthermore, the High-Performance Liquid Chromatography (HPLC) analysis indicated that all extracts of M. aquatica were abundant in noteworthy phytochemical compounds, especially gallic acid, vanillic acid, chlorobenzoic acid, quercetin, and kaempferol. Furthermore, the results indicated that the total phenolic content was higher in hydroethanolic extract (62.19 ± 1.19 mg GAE/g DW) in contrast to the acetonic and aqueous extracts (22.22 ± 0.64, and 22.44± 0.57 mg GAE/g DW) respectively. Similarly, the aqueous ethanol extract contained the greatest flavonoid concentration, with values of 29.15± 0.09 mg QE/g DW when compared with the other extracts. The seam extract poses excellent antioxidant power with an IC50 of 0.06 ± 0.00 mg/mL for the DPPH test, and lower RP with EC50 of 80± 0.00 µg/ml when compared with acetonic and aqueous extract (370± 0.00 and 460± 0.01 µg/mL) respectively. Moreover, the hydroethanolic extract has a high level of TAC 75.09± 2.00 mg EAA/g DW, followed by aqueous extract carrying a value of 28.53 ± 1.36 mg EAA/g DW. The antibacterial capacity is ranged between 0.78 ± 0.05 mg/mL and 12.60 ± 0.00 mg/L. The results of the in-silico study demonstrated that quercetin, vanillic acid, and naringenin components contribute to the antioxidant capability. While gallic acid, kaempferol, and quercetin components are attributed to the antibacterial capacity.

The use of optical fibers is increasing in modern aircraft because it helps solve challenges of size, weight, communication, and reliability in new aircraft generation. This work describes a video and power transmission system using optical fibers (PoF) for in-flight entertainment (IFE) system application. We present the benefits and the limitations of this application, and we perform two practical experiments to demonstrate their performance. It used off-the-shelf devices in the experiments, such as one 15-W semiconductor laser operating at 808 nm, GaAs photovoltaic converters, optical transmitters and receivers, and video monitors. The power and video signals were transmitted using two 50-m multimode fibers. In addition, we proposed and tested two types of energy transformation units (ETU), which are responsible for supplying electrical energy to the IFE video monitor and the optical fiber receiver.

In the field of human in vitro fertilization (IVF), selecting the best oocyte for freezing or embryo for transfer remains an important focus of clinical practice. Although several techniques are and have been used for this goal, results have generally not been favorable and/or are invasive such that damage to some embryos occurs, resulting in a reduced number of healthy births. Therefore, the search continues for non-invasive oocyte and embryo quality markers that signal the development of high-quality embryos. Multiple studies indicate the important positive effects of retinoic acid (RA) on oocyte maturation and function. Here, we present evidence that part of these effects are via the ability of RA to regulate the activity of connexin 43 (Cx43), the main subunit of gap junction channels in human cumulus granulosa cells (CGC). These channels play an important role in regulating the micronutrient environment of the oocyte by allowing the transfer of ions, metabolites, and small molecules. Multiple studies have demonstrated the requirement for Cx43 in CGC for the normal progression of folliculogenesis, and that increased expression of this connexin is linked to improved developmental competence of the oocyte. The data has shown that RA can up-regulate gap junction intercellular communication (GJIC) in the cumulus-oocyte complex by a non-genomic mechanism that results in the dephosphorylation of Cx43 and enhanced GJIC. Recognizing the positive role played by gap junctions in CGC on oocyte development and the regulation of Cx43 by RA, the findings have highlighted the possibility that CGC RA levels may serve as a non-invasive indicator for selecting high-quality oocytes for IVF procedures. In addition, the data suggests that manipulation of Cx43 with retinoid compounds could provide new pharmacological approaches to improve IVF outcomes in cases of failed implantation, recurrent miscarriage, or in certain diseases that are characterized by reduced fecundity, such as endometriosis.

The alarming rise of antibiotic resistance has made it imperative to find novel antimicrobial medications. This study reports the design and synthesis of new molecules based on benzofu-ran-pyrazole scaffolds hybridized with various N/O heterocycles using the molecular hybridiza-tion process. The newly synthesized candidates were confirmed using micro-analytical and spectral analyses, and their antimicrobial characteristics were assessed against different bacterial and fungal isolates in comparison with novobiocin and clotrimazole as antibacterial and anti-fungal standards, respectively. In addition, the new compounds were further evaluated as in vitro antioxidants and anti-inflammatory congeners. The most promising broad spectrum antimicrobial compounds 9, 10 with values ranging from 2.50-20.60 μg/mL were further examined as E. coli DNA gyrase B enzyme suppressors using novobiocin as a reference drug. In silico computational and ADMET studies were carried out for the most active compounds.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

In silico prediction of the in vivo efficacy of siRNA ionizable-lipid nanoparticles is desirable yet never achieved before. This study aims to computationally predict siRNA nanoparticles in vivo efficacy, which saves time and resources. A data set containing 120 entries was prepared by combining molecular descriptors of the ionizable lipids together with two nanoparticles formulation characteristics. Input descriptor combinations were selected by an evolutionary algorithm. Artificial neural networks, support vector machines and partial least squares regression were used for QSAR modeling. Depending on how the data set is split, two training sets and two external validation sets were prepared. Training and validation sets contained 90 and 30 entries respectively. The results showed the successful predictions of validation set log(dose) with R2val = 0.86 – 0.89 and 0.75 – 80 for validation sets one and two respectively. Artificial neural networks resulted in the best R2val for both validation sets. For predictions that have high bias, improvement of R2val from 0.47 to 0.96 was achieved by selecting the training set lipids lying within the applicability domain. In conclusion, in vivo performance of siRNA nanoparticles was successfully predicted by combining cheminformatics with machine learning techniques.

The absorption of medium-chain fatty acids (MCFA) depends on the solubility of these components in the gastric fluid. Parameters such as the total MCFA concentration, carboxyl ionization level, and carbon chain length affect the solubility of these molecules. Moreover, the enzymatic lipolysis of solubilized triacylglycerol (TAG) molecules may depend on the carbon chain length of the fatty acids (FAs) components and their positions on the glycerol backbone. This present study aimed at investigating the effect of electrolyte usually formed during the gastric digestion phase on the solubility of MCFA, and evaluating the influence of the FA carbon chain length on the lipolysis rate during the in vitro digestion simulation. The results obtained here showed that the increasing of electrolyte concentrations tend to decrease the mutual solubility of systems composed by the caproic and caprylic fatty acids + sodium chloride, sodium bicarbonate, and potassium chloride solutions. We also observed that a conventional version of the thermodynamic UNIQUAC model was able to correlate the liquid-liquid phase behavior of the electrolyte solutions. Regarding the in vitro digestion simulation, the experimental data indicated that the action of the pancreatic enzyme occurred preferentially in TAG molecules comprised of short and medium-chain fatty acids.

There is a growing need for novel in vitro corneal models to replace animal-based ex vivo test in drug permeability studies. In this study we demonstrate a corneal mimetic that models the stromal and epithelial compartments of human cornea. Human corneal epithelial cells (HCE-T) were grown on top of a self-supporting porcine collagen-based hydrogel. Cross sections of the multilayers were characterized by histological staining and immunocytochemistry of zonula occludens-1 protein (ZO-1) and occludin. Furthermore, water content and elastic properties of the synthetized collagen type I-based hydrogels were measured. The apparent permeability coefficient (Papp) values of a representative set of ophthalmic drugs were measured and correlated to rabbit cornea Papp values found in the literature. Multilayered structure of HCE-T cells and expression of ZO-1 and occludin in full thickness of multilayer were observed. The hydrogel-based corneal model exhibited excellent correlation to rabbit corneal permeability (r=0.96), whereas insert-grown HCE-T multilayer was more permeable and the correlation to the rabbit corneal permeability was lower (r=0.89). The hydrogel-based human corneal model predicts the rabbit corneal permeability more reliably in comparison to HCE-T cells grown in inserts. This in vitro human corneal model can be successfully employed for drug permeability tests whilst avoiding ethical issues and reducing costs.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

Information on the nutritive value and in vitro fermentation characteristics of native shrubs in New Zealand is scant. This is despite their potential as alternatives to exotic trees and shrubs for sup-plementary fodder, and mitigation of greenhouse gas and soil erosion on hill country sheep and beef farms. The objectives of this study were to measure the in vitro fermentation gas production, predict parameters of in vitro fermentation kinetics and to estimate in vitro fermentation of volatile fatty acids (VFA), microbial biomass (MBM) and greenhouse gases of four native shrubs (Coprosma robusta, Griselinia littoralis, Hoheria populnea and Pittosporum crassifolium) and an exotic fodder tree species, Salix schwerinii. Total in vitro gas production was higher (p<0.05) for natives than S. schwerinii. Prediction using the single pool model resulted in biologically incorrect negative in vitro total gas production from the immediately soluble fraction of the native shrubs. However, the dual pool model better predicted in vitro total gas production and was in alignment with measured in vitro fermentation end products. In vitro VFA and greenhouse gas production from fermentation of leaf and stem material were higher (p<0.05), and MBM lower (p<0.05), for native shrubs com-pared to S. schwerinii. The lower in vitro total gas production, VFA and greenhouse gases produc-tion, and higher MBM of S. schwerinii may be explained by the presence of condensed tannins (CT), although this was not measured and requires further study. In conclusion, results from this study suggests that when consumed by ruminant livestock, the browsable native shrubs can provide adequate energy and microbial protein, and that greenhouse gas production from these species is within ranges reported for typical New Zealand pastures.

In the recent years, Cannabis and hemp-based products have become increasingly popular for various applications ranging from recreational use, edibles, beverages to health care products and medicines. The rapid detection and differentiation of phytocannabinoids is, therefore, essential to assess the potency, therapeutic and nutritional values of cannabis cultivars. Here, we implemented the SpiderMass technology for the in vivo detection of cannabidiol acid (CBDA) and tetrahydrocannabinol acid (THCA) and other endogenous organic plant compounds to access distribution gradients within the plants and differentiate cultivars. The SpiderMass system is composed of an IR- laser handheld microsampling probe connected to the mass spectrometer through a transfer tube. The analysis was performed in situ on different plant organs from freshly cultivated Cannabis plants in only a few seconds. SpiderMass analysis easily discriminated the two acid phytocannabinoid isomers by MS/MS and the built statistical models differentiated between four Cannabis cultivars. Different abundancies of acid phytocannabinoids were also found along the plant as well as between different cultivars. All together, these results introduce the direct analysis by SpiderMass as a compelling analytical alternative for forensic and hemp industrial analysis.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

Objective: Ensuring bone health is crucial for preventing conditions such as osteoporosis and fractures. Zingerone, a phytochemical compound, has gained attention for its potential benefits in bone health. This study evaluated the osteoprotective potential of zingerone and its effects on differentiation and signalling pathways in vitro using SAOS-2 osteosarcoma and RAW264.7 macrophage cell lines, aiming to elucidate its mechanism of action in bone metabolism. Methods: SAOS-2 osteosarcoma and RAW264.7 macrophage cells were treated with zingerone at concentrations of 0.1-200µM. Osteoblast differentiation was assessed by alkaline phosphatase (ALP) activity, bone mineralisation via alizarin red S stain and gene expression markers (ALP, runt-related transcription factor 2 (Runx2) and osteocalcin) via quantitative polymerase chain reaction. Osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity and mitogen-activated protein kinase (MAPK) pathways. Results: Zingerone at 200µM, did not significantly enhance mineralization in SAOS-2 cells, but upregulated ALP and Runx2 gene expression (p<0.05). Moreover, zingerone significantly inhibited osteoclast differentiation in RAW264.7 cells as evidenced by reduced TRAP staining and activity (p<0.05). Conclusion: The moderate anti-osteoclastic effects of zingerone suggest its potential role in preserving bone mass by reducing bone resorption. This study provides new insights into how zingerone modulates bone cell activity, highlighting its potential as a dietary supplement for bone health. Further research, including its underlying mechanisms for bone-related disorders and in vivo and clinical studies, is needed to fully understand its clinical relevance in bone-related disorders.

The Fading Affect Bias (FAB) occurs in autobiographical memory when unpleasant emotions fade faster than pleasant emotions and the phenomenon appears to be a form of emotion regulation. As emotion regulation is positively related to problem-solving, the current study examined FAB in the context of problem-solving. In-person and online studies asked participants to provide basic demographics, describe their problem-solving abilities, and rate various healthy and unhealthy variables including emotional intelligence and positive problem-solving attitudes. Participants also completed an autobiographical event memory form for which they recalled and described 2 pleasant and 2 unpleasant problem-solving and non-problem-solving events and rated the initial and current affect and rehearsals for those events. We found a robust FAB effect that was larger for problem-solving events than for non-problem-solving events in Study 1 but not in Study 2. We also found that FAB was positively related to healthy variables, such as grit, and negatively related to unhealthy variables, such as depression. Moreover, many of these negative relations were inverted at high levels of positive problem-solving attitudes, and these complex interactions were partially mediated by talking rehearsals and thinking rehearsals.

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

In the context of improving aircraft safety, this study focuses on the development and evaluation of a graphene-based ice detection system using an environmental chamber. The research is driven by the need for more accurate and efficient ice detection methods, crucial in mitigating in-flight icing hazards. The methodology employed involves testing flat graphene-based sensors in a controlled environment, simulating a variety of climatic conditions that could be experienced in an aircraft during its entire flight. The environmental chamber enabled precise manipulation of temperature and humidity levels, thereby providing a realistic and comprehensive test bed for sensor performance evaluation. The results were significant, revealing the graphene sensors’ heightened sensitivity and rapid response to the subtle changes in environmental conditions, especially the critical phase transition from water to ice. This sensitivity is the key to detecting ice formation at its onset, a critical requirement for aviation safety. The study concludes that graphene-based sensors, tested under varied and controlled atmospheric conditions, exhibit a remarkable potential in enhancing ice detection systems for aircraft. Their lightweight, efficient and highly responsive nature makes them a superior alternative to traditional ice detection technologies, paving the way for more advanced and reliable aircraft safety solutions.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

Background: Over the past few years there has been immense evolution in various areas particularly in the areas of digital technologies wherein the pace of change is very high. Industrial areas such as operations and supply chain management together with advanced technologies such as machine learning, big data analytics, artificial intelligence, as well as the Internet of Things, create completely different forms of operational models for various industries. In the area of healthcare too, these emerging computational sophistication is introduced to revolutionise the approaches to prevent, diagnose and treat diverse diseases and illnesses. Objective: The objective of this study is to provide an extensive review of the contemporary approaches utilizing data to cope with significant mental disorders. From over 60 relevant scholarly articles published between 2011 and 2023, it discusses how tools such as predictive modelling, social media analysis, data from smartphones, and chatbots help with issues such as early detection, telemonitoring, provision of psychological support, and individualised prevention. Method: An initial literature review to analyse over 60 research articles, which include empirical studies that were conducted between 2011 and 2023. The research assessed implemented novel digital approaches to mental health interventions including big data analytics for predicting condition status, machine learning for examining social media content, behaviour monitoring through smartphone sensors, and using conversational agents or chatbots. The following is an overview of general conclusions from experimental and descriptive secondary research studies published in professional outlets concerning possible advantages and disadvantages of data science applied to important concerns in mental health. Results: Research reveals that integrating subtle e-health tools in tandem with typical treatment approaches holds the potential to expand mental health services to more or less integrate them into clients’ day-to-day lives, and practically individualize effective treatments accordingly. Technological solutions for instance allow remote risk assessment, symptom monitoring and determination of treatment compliance. New lines of virtualized paradigm solve social challenges that interfere with the conventional provision and consumption of care. However, questions of privacy and the long-term effects as well as clinical adoption are yet to be solved in a analytically distinct manner.

In the contemporary era, the movement for women empowerment is not merely a social cause but a transformative force reshaping societies across the globe. The article "Breaking Barriers: Women Empowerment Transforming Societies in Modern Times Building a Better Future" delves into the multifaceted impact of empowering women, highlighting how it transcends individual upliftment and fosters widespread societal progress. It also delves into the transformative impact of women’s empowerment on societies, highlighting successful initiatives, case studies, and personal narratives that illustrate the journey towards gender parity. It examines the challenges and opportunities in this ongoing struggle, emphasizing the need for continued advocacy, education, and policy reform. By fostering an environment where women can thrive, societies can unlock unprecedented potential and build a better, more prosperous future for all. By examining key areas such as education, economic participation, political representation, and social inclusion, the article elucidates how empowering women leads to more equitable, prosperous, and resilient communities. It underscores the importance of dismantling historical and cultural barriers that have long hindered women's potential, while celebrating the strides made towards gender equality. Furthermore, the narrative showcases inspiring stories of women leaders, entrepreneurs, and change-makers who are spearheading efforts to build a better future for all. This exploration not only emphasizes the moral imperative of gender equality but also its critical role in driving sustainable development and global advancement.

Keywords: Artificial Intelligence in Implantology; AI in Dental Implantology; Machine Learning in Dental Implantology; Deep Learning in Implant Dentistry; Robotics in Dental Implantology; AI-Based Implant Planning.

Simple Summary: This review explores the origin of Leukemic Stem-Like Cells (LSLCs) from (Very) Small Leukemic Stem-Like Cells ((V)SLSLCs) and Cancer Stem Cells (CSCs) from trans-formed Very Small Embryonic-Like Stem Cells (VSELSCs). Understanding this relation is a step toward uncovering the mechanisms behind cancer and leukemia initiation and development. We explore how these very small precursor cell stages might contribute to the initiation and progres-sion of cancer as well as leukemia with a focus on Acute Myeloid Leukemia (AML) as a model. Abstract: Recent experimental findings indicate that CSCs originate from transformed VSELSCs, which are early precursor stages of healthy stem cells. This discovery marks a crucial step in understanding the mechanisms that drive cancer development and initiation. Our team's follow-up studies on leukemia, lung cancer, and healthy embryonic kidney cells have, for the first time, identified stag-es resembling very small precursor stem cells in continuously growing cell lines. These findings suggest the existence of (Very) Small Cancer Stem Cells ((V)SCSCs) or (V)SLSCs within respective subpopulations of CSCs and LSCs in vivo. In this review, we explore theoretical examples of how leukemia progresses through various stages, highlighting the role of these very small precursor cells as fundament primitive stages. We also discuss the potential implications of further research into these unique cellular stages for advancing cancer and leukemia treatment and prevention strategies.

Chlamydia trachomatis (CT) is an obligate intracellular bacterial pathogen known to cause trachoma, sexually transmitted infections, and reactive arthritis. The more serious sequelae of these diseases, blindness from trachoma and pelvic inflammatory disease from chlamydial STD are immunopathological responses to chronic infections. With the abundance of dendritic cells in CT infection sites and their central importance in immune regulation, the susceptibility of dendritic cells to CT infection was investigated in vitro. CT (serovar F) was grown and extracted from HeLa 229 cells for infection of human dendritic cells (DCs). Human DCs were generated from peripheral blood mononuclear cells in the presence of GM-CSF and IL-4. Infected DCs were harvested at 0, 4, 24, and 48 h after infection and immunostained. Results from fluorescence microscopy showed that DC can be infected and can support the growth of CT in vitro. Intracellular elementary and reticulate bodies of CT were detected, and reticulate bodies were shown to multiply over the 48 h-cycle in DC. At 48 h, intracellular elementary bodies were detected in some DCs. These results may provide new insights into the possible participation of DC in sustaining chronic or latent infection, or even dissemination of CT infection to other sites.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC₅₀ value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile. The current study provides insight for further investigation of the antitumour potential of the molecule.

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

Phytochemicals from Hedera helix L. lead to extracts with good biological properties which are beneficial to human health and can be used to protect plants against different diseases. The aim of this research was to find the most suitable extraction method and the most favorable parameters for different bioactive compounds extraction from ivy leaves. Different extraction methods, namely microwave assisted extraction (MAE), ultrasound assisted extraction (UAE), and conventional heating extraction (CHE), were used. The most suitable method for saponins extraction is MAE with an extraction efficiency of 58%, while for carbohydrates and polyphenols the best results were achieved by UAE with an extraction efficiency of 61.7% and 63.5%, respectively. The antioxidant activity (AA) of the extracts was also determined. The highest AA was obtained by UAE (368.98±9.01 µmol TR/gDM). Better results were achieved at 50 °C for 10 min of extraction, using 80% ethanol in water as solvent. In order to evaluate their in vitro cytotoxicity, the extracts richest in bioactive compounds were tested on NCTC fibroblasts. Their influence on the DNA content of RAW 264.7 murine macrophages was also tested. Until 200 µg/mL, the extracts obtained by UAE and MAE were cytocompatible with NCTC fibroblasts at 48 h of treatment.

Vitamin D3 deficiency is a global phenomenon, which can be coped with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors, such as matrix composition and interactions throughout the gastrointestinal tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, and the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the vitamin D3 initial content in supplements and foods, as well as after each digestion stage. Results indicated that foods exhibited higher bioaccessibility indices compared to supplements, and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e. gastric pH=1) enhances vitamin’s bioaccessibility.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

Leptospirosis remains an important worldwide zoonotic disease caused by Leptospira spp affecting human and animals. This research aims to study the virulent-associated secreted proteins (protein secretome) of pathogenic Leptospira interrogans serovar Icterohemorrhagiae strain RGA (Leptospira RGA) transition from the environment to mammalian physiological osmolarity, temperature (37 °C) and carbon dioxide concentration (5% CO2) conditions for 24 h. Mass Spectrometry and bioinformatics approaches, we identified 69 potential secreted proteins from the culture supernatant of the Leptospira RGA isolate. We discovered transporters and porins such as phosphate porin, outer membrane efflux, ompA family protein, and polymer-forming cytoskeletal family protein under hyperosmotic condition. Under heat stress, degradation enzymes included zinc metallopeptidase, M23 family (LA3456, LA0709), Rhs family protein (LA1765), thermolysin metallopeptidase; / hydrolase family (LA1345, LA2501). Oxidative stress response proteins induced by osmolarity and temperature shifts included chaperon GrpE, DnaK (LA3705), antioxidants, i.e., thiol-specific redoxin, and peroxiredoxin (LA2809). In response to the in vivo transition, metabolic and other enzymes involved in energy production (COG:C), amino acid metabolism and transport (COG:E), and lipid metabolism and transport (COG:I), as well as moonlighting proteins functionally binding to plasminogen and fibronectin and regulating transcription, were also discovered. An overview of secreted proteins will supplement our understanding of Leptospira biology and pathogenesis during infection and also in response to environmental stimuli and their potential virulent determinants have the potential for developing leptospirosis vaccines and diagnosis.

Recent discoveries of potential ice particles and ice-cemented regolith on celestial bodies like the Moon and Mars have ushered in new opportunities for developing technologies to extract water, facilitating future space missions and activities on these celestial surfaces. This study delves into the potential for water extraction from regolith through an experiment designed to test water recuperation from regolith simulant under varying gravitational conditions. The resultant water vapor extracted from the regolith is re-condensed on a substrate surface and collected in liquid form. Three types of substrates, hydrophobic, hydrophilic, and grooved, are explored. The system’s functionality was assessed during a parabolic flight campaign simulating three distinct gravity levels: microgravity, lunar gravity, and Martian gravity. Our findings reveal that the hydrophobic surface demonstrates the highest efficiency due to drop-wise condensation, and lower gravity levels result in increased water condensation on the substrates. This experiment aims to provide insights into in-situ water recovery, which is pivotal for establishing economically-sustainable water supplies for future missions.

Background: One of the main diseases of worldwide concern is non–insulin dependent Diabetes mellitus. 90-95% of patients with diabetes suffers from Type II diabetes, a metabolic diabetes whose prevalence is increasing in the world.Given the current prevalence of diabetes type II in society, research of natural compounds able to regulate glycaemia and insulin–resistance is nowadays covering importance, as alternative or co–adjuvant treatment to existing hypoglycaemic medicines. In pre–clinical steps of research, C. elegans is considered a promising in vivo model for the study of the molecular mechanism of glucose as part of anti–diabetic bioactivity.Most of the studies of insulin resistance with this in vivo model are carried out by using mutant strains such as daf-2 and the effects of the compounds are attributed a posteriori, after a physiological response of the worms rather than directly measuring preservation of activity inside the worm. Methods: The in vitro α-glucosidase inhibition of two oral formulations with Origanum vulgare extract before and after a simulated process of gastrointestinal digestion was evaluated. After confirming the in vitro activity, the α-glucosidase inhibition was tested in vivo through the new method proposed. Results: The crude extract showed an IC50 value similar to acarbose (positive control), before and after the gastrointestinal digestion. The encapsulated extract (111.86±1.25 µg/mL) did not present statistical differences with the positive control (110.10±1.15 µg/mL) after digestion. However, the powder formulation showed the highest hypoglycaemic activity (59.55±0.85 µg/mL).In vivo, the IC50 values showed similar profile than in vitro. Conclusion: A new simple and reliable method has been developed to determine pharmacological activities inside in vivo model C. elegans.The method has been evaluated with a hydroalcoholic extract of O. vulgare. The method is accurate and valid for the quantification of the inhibition of in vivo, allowing the direct attribution of this in vivo hypoglycaemic activity to the treatment. In addition, it opens the door to further research into in vitro pharmacological activities that require an in vivo counterpart.

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase is a cell surface receptor whose overexpression has been associated with different types of cancers including brain cancer (glioblastoma multiforme). The ability of the extract of Scutellaria baicalensis to inhibit the proliferation of malignant glioma cells have been reported. Thus, in this study we report the identification of 307 bioactive constituents responsible for the anti-glioblastoma multiforme effect from S. baicalensis using in silico studies such as molecular docking, binding free energy calculations, pharmacophore modelling, induced-fit docking, gene enrichment analysis, molecular dynamic simulations and ADMET predictions. A total of 307 chemical constituents of S. baicalensis were screened and the top 10 scoring compounds indicated different binding affinities ranging from -9.010 to -6.427 kcal/mol towards the EGFR tyrosine kinase; Ganhuangenin, 5,7,2',5'-tetrahydroxyflavone, (2R)-2-(2,6-dihydroxyphenyl)-3,4-dihydro-2H-chromene-5,7-diol, and tenaxin I possess higher binding affinities (-9.010 to -8.649 kcal/mol) compared to the standard ligand, erlotinib having -8.539 kcal/mol. The compounds interacted with amino acids of clinical importance such as MET 769, GLU 738, THR 766 via H-bond. The structural features involved in the interaction with the target were mostly two aromatic rings, H-bond donors and acceptors and some hydrophobic interactions which varies between the ligands. Better docking scores in the induced-fit docking further validates the inhibitory potential of the compounds against the flexible protein. All the top-scoring ligands from S. baicalensis had zero Lipinski violation and also obeyed other drug-likeness rules by Ghose, Veber, Egan, and Muegge with the exception of breviscapine. Interestingly, all the compounds are not likely to be hepatotoxic, mutagenic, or cytogenic, making them potentially safe as anti-cancer agents.

This study comprehensively explores Serbia's Disaster (Risk) Management System, aiming to critically evaluate its inherent strengths and weaknesses. Using descriptive-analytical methods and qualitative interpretation, SWOT analysis was applied to collect data from scientific papers, books, and institutional reports. This study delves deeply into the nuances of Serbia's Disaster Management Framework, revealing a nuanced landscape of strengths, weaknesses, and strategic improvement opportunities. Identified strengths underscore a robust foundation characterized by proficient professionals, state-of-the-art technology, and cohesive teamwork, all pivotal for effective emergency preparedness and response. Conversely, weaknesses underscore pressing imperatives for enhancements in regulatory enforcement, resource allocation, and infrastructure upgrades, presently hampering the framework's efficacy and response readiness. This research contributes to the ongoing discourse on disaster risk management and serves as a catalyst for further scholarly inquiry and policy formulation. By mapping out the structure of Serbia’s Disaster (Risk) Management Framework and integrating diverse data sources, the study enriches theoretical models and lays the groundwork for practical policy interventions. Its findings, including precise recommendations for policy reform and strategic improvements, provide valuable insights for policymakers, emergency management experts, and stakeholders seeking to enhance disaster preparedness and response capabilities on both national and global scales.

Aflatoxins in feeds cause great health hazards to animals and in advance, to human. Potential of crude clays designated AC, KC, CC and MC and ashes VA and RA were evaluated for their capacity to adsorb aflatoxins B₁ (AFB₁), B₂ (AFB₂), G₁ (AFG₁) and G₂ (AFG₂) relative to a commercial binder Mycobinder^R (Evonik Industries AG) using in-vitro technique. On average, CC, VA, KC, MC, AC, RA and Mycobind^R adsorbed 39.9%, 51.3%, 61.5%, 62.0%, 72.6%, 84.7% and 98.1% of the total aflatoxins in buffered solution, respectively. The capacity of AC and RA was statistically (p<0.05) better in binding aflatoxins next to Mycobind^R. Capacity of the TBM and Mycobind^R to bind aflatoxins, seemed to follow the trend of their cation exchange capacity (CEC). The CEC (meq/100g) of CC, MC, KC, VA, AC, RA and Mycobind^R were 7.0, 15.4, 18.8, 25.4, 27.2, 27.2 and 38.9, respectively. On average 96.3%, 42.7%, 80.8% and 32.1% of AFB1, AFB2, AFG1 and AFG2 were adsorbed, respectively. Binding capacity of the clays and ashes relative to Mycobind^R was about 100% for AC and RA, 50% for KC, MC and VA and 33.3% for CC. The AC and RA seem to be promising resources in binding aflatoxins in solution.

The formula Chong-Lou-Yao-Fang (CLYF) is an herbal medicinal formulation developed by the indigenous Naxi people for treating liver cancer. This study is to reveal the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment through network pharmacology, molecular docking and in vitro experiments. 35 key compounds were screened from 176 active ingredients in CLYF, which played a vital role in the treatment of cancer, 20 core targets were filtered through protein–protein interaction (PPI) network analysis. The enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that PI3K-Akt, MAPK, hepatitis B, hepatitis C might be effective in liver cancer treatment. Mo-lecular docking revealed stable binding between EGFR, TP53, and AKT1 with active ingredients. Experiments with cell cultures confirmed that CLYF-A suppressed the proliferation of HepG2 cells, which is consistent with the network pharmacology approach undertaken and the predictions of molecular docking. CLYF-A also induced significant apoptosis and cell cycle arrest in HepG2 cells, which was associated with the loss of mitochondrial membrane potential. This study explored the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment. Our results may provide a scientific basis for the clinical use of CLYF for cancer treatment and have important implications for developing pharmaceutical preparations, which also need more phar-macological experiments.

Confined masonry (CM) is a construction system which consists of masonry wall panels enclosed by vertical and horizontal reinforced concrete confining elements. The presence of these confining elements distinguishes CM from unreinforced masonry system and makes this technology suitable for construction of structures in regions subjected to intense seismic or wind actions. CM construction has been used in many countries and regions, and has performed well in past earthquakes. The purpose of the paper is to review past research studies related to the seismic in-plane and out-of-plane behaviour of CM structures. The authors have identified the key design and construction parameters which were considered in past research studies and have performed statistical analyses to establish their influence on the seismic performance of CM buildings. For the purpose of this study the authors have compiled databases of previous experimental studies on CM wall specimens which were used for statistical analyses. Finally, the paper discusses research gaps and needs for future research studies which would contribute to the understanding of seismic behaviour and failure mechanisms of CM walls.

Biomimetic foods are expected to have potential health benefits for the management and prevention of chronic diseases, such as diabetes and cardiovascular disease. In the current research, two commercially available and affordable plant proteins (soy protein isolate-SPI and pea protein isolate-PPI) at two levels (5%, 10%) were added to the Yangyu jiaotuan with an objective to develop a product with reduced glycemic properties and high protein content while maintaining its original taste and texture. The results showed that several important textural properties such as hardness and chewiness did not change significantly during the refrigerated storage. The storage modulus G′ increased with refrigerated storage time for different samples, there were significant differences among the five samples (with and without protein addition) with respect to frequency dependence during rheological measurements. The in vitro starch digestion experiments showed that the starch hydrolysis of Yangyu jiaotuan decreased considerably with the increase in PPI content and during refrigerated storage due to starch retrogradation. Protein has protected the microstructure and there was less damage when compared to samples without protein. The bimodal peaks of the particle size distribution curves showed that the newly developed Yangyu jiaotuan contains two different sizes of particles, the smaller particles (~30 μm) corresponded to PPI and starch granules, while the larger particles corresponded to the fragments of gel network of the starch matrix. Based on the above results, Yangyu jiaotuan mixed with pea protein is a convenient potato staple food product, which complies with the biomimetic potato food very well.

This research evaluated the role and feasibility of the granular nanocellulose particles (GNC) from sugarcane bagasse obtained from enzymatic hydrolysis in reducing lipid digestibility and permeability in the in vitro simulated gastrointestinal (GI) system. GNC concentration (0.02%, w/v) had significantly affected the released free fatty acid (FFA) reduction of approximately 20%. The Pick-ring emulsion of the GNC and olive oil simulation mixture revealed higher oil droplet size distribution and stability in the initial stage than the vortexed mixture formation. The difference in particle size distribution and zeta potential of the ingested GNC suspension and GNC-olive oil emulsion were displayed during the in vitro gastrointestinal simulation. GNC particles interacted and distributed surrounding the oil droplet leading to the interfacial emulsion. The GNC concentration (0.01-0.10%, w/v) showed low toxicity on the HIEC-6 cell, ranging from 80.0 to 99% of cell viability. The release of FFA containing the ingested GNC suspension and GNC-olive oil emulsion was about 30% reduction compared to without GNC digest solution. The FFA and triglyceride permeability through the HIEC-6 intestinal epithelium monolayer were deceased in the digesta containing the ingested GNC and emulsion. This work indicated that GNC represented a significantly critical role and properties in the GI tract and reduced lipid digestion and absorption. This GNC could be utilized as an alternative food additive or supplement in fatty food for weight control due to their inhibiting lipid digestibility and assimilation.

Bioactive peptides are sequences of amino acids, cut from the parent protein with en-zymes or high pressure processing that can impart a tertiary health benefit to the con-sumer that goes beyond basic human nutrition. This study explores mesopelagic fish in-cluding Maurolicus muelleri and Benthosema glaciale as sources of peptides with an-ti-inflammatory, heart health beneficial, antioxidant and other bioactivities. Bioactive peptides were generated post-catch using different enzymatic hydrolysis processes ap-plied to mesopelagic species caught from experimental cruises targeting these fish. Maurolicus muelleri and Benthosema glaciale were the dominant species processed. Bi-oactive hydrolysates included a Maurolicus muelleri Alcalase hydrolysate and a Maurolicus muelleri autolysis. Hundreds of peptide sequences were identified using mass spectrome-try from active hydrolysates. In silico analysis was used to rank identified peptide se-quences in terms of overall bioactivity using Peptide Ranker, anti-inflammatory activity using PrepAIP, ability to impart Umami flavours with Umami-MRNN and dipeptidyl peptidase IV inhibitory potential using AntiDMPpred . Thirty peptides were selected fol-lowing in silico analysis. Several of the selected peptides had sequence homology with peptides derived from other fish proteins including Atlantic salmon (peptide QCPLHR-PWAL) and thin-lipped mullet (peptide FDAFLPM). Seven peptides predicted to have an-ti-inflammatory, anti-type 2 diabetes or Umami potential using in silico strategies were chemically synthesized and their anti-inflammatory activities confirmed using in vitro bioassays with COX-1 and COX-2 enzymes. The peptide QCPLHRPWAL inhibited COX-1 and COX-2 by 82.90% (+/-0.54) and 53.84% respectively and had a selectivity index greater than 10. This peptide warrant further research as a novel anti-inflammatory/pain relief peptide. Other bioactivities associated with DPP-IV inhibition and Umami flavours de-velopment are discussed. Identified peptides offer potential for use in functional foods or topical agents to prevent pain and inflammation associated with diseases like psoriasis, arthritis and inflammatory bowel disease, however further research in vivo is required.

The majority of skin cancers are caused by over exposure to ultraviolet (UV) radiation. The effects of UV radiation on the expression of drug transporters expressed in human skin has never been studied. In this the effects of UVA and UVB irradiation on the expression of ATP-binding cassette (ABC) transporters and Solute carrier (SLC) transporters was evaluated in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) in primary culture. First experiments were intended to validate the inflammatory reaction in response to stimulation by lipopolysaccharide (LPS) in NHEK, NHDF and 3D-reconstructed human epidermis (3D-RHE) model. LPS treatment has shown to increase the expression of IL-8 and TNF-alpha in all three in vitro models. Expression of the most expressed ABC and SLC transporters was then measured in NHEK and NHDF after UVA (30 J/m²) and UVB (40 mJ/m²) irradiation. The most striking result was a significant 29-fold increase of the expression of SLCO4A1 in normal human dermal fibroblasts. In summary, this study shows for the first time a significant regulation of the expression of SLCO4A1 in human dermal fibroblasts induced by UVA irradiation. This finding is of particular interest as most of skin cancers are caused by over exposure to ultraviolet radiation and need to be considered in pharmacokinetic evaluation of topical drugs.

This work presents the possibility of using a synthetic membrane for pretracing mucosal penetration studies. The permeability of two types of membranes, porcine oral mucosa and a synthetic Nuclepore membrane, to water was compared. Moreover, the water permeability of membranes modified with waterproofing formulations was measured to study their ability to protect against the penetration of viruses, toxins, etc. A very good correlation was obtained between the transmucosal water loss (TMWL) values of the artificial membrane and the mucosa. These results support the possible use of this synthetic membrane in the screening of the water permeability of formulations. In addition, studies of the permeation of different actives, drugs and biocides through the two membranes were carried out, and these results were compared with their skin permeation data. The synthetic membrane does not seem to discern between compounds in terms of permeability, which could be due to the lack of lipids in the composition of this synthetic membrane. Therefore, Nuclepore alone cannot be used as a model for the release of actives. Additionally, the permeation of caffeine through intact or modified membranes incorporating waterproofing formulations was also studied. In this case, similar permeation profiles through the synthetic membrane and mucosa were found. The results from these assays should lend support to the use of this synthetic membrane when screening formulations to be applied in oral penetration studies.

In this study, four experimental treatments were evaluated: (T1) alfalfa hay + concentrate, (50:50%, DM); (T2) alfalfa hay + Leucaena leucocephala + concentrate, (30:20:50%, DM); (T3) alfalfa hay + prickly pear + concentrate, (30:20:50%, DM); and (T4) alfalfa hay + Leucaena leucocephala + prickly pear + concentrate, (30:10:10:50%, DM). NH3-N concentrations in T2 and T4 decreased when replaced alfalfa hay in 20 and 10 %, respectively. Treatments did not affect the concentration of total volatile fatty acids (TVFA) between T3 and T4 (p>0.05); while the concentrations among T1 and T2 were different (P<0.05). T2 showed a reduction of 25.5 % in the methane production when compared to T1(p < 0.05).The lowest concentrations of protozoa were observed in T2 and T4, which contained Leucaena leucocephala (T2) and Leucaena leucocephala + prickly pear (T4) (p<0.05). The highest concentration of total methanogens was recorded in T1 and were different to T2, T3 and T4 (p<0.05). Leucaena leucocephala at a inclusion percentage of 20 % decreased the methane when compared to T1; whereas prickly pear there was not a positive effect the methane production.

Soups show diverse health functions, which should be related with their nutrient profiles. NMR spectroscopy is a robust, sensitive and rapid method to unveil or identify the chemical composition of food or food-derived metabolites. In the current study, 1H-NMR spectroscopy approach was applied to identify the metabolic profiling of two kinds of home-cooked freshwater fish soups (crucian carp and snakehead fish) before and after in vitro gastrointestinal digestion. The nutritional profiles of these two kinds of soups were identified at first. With the help of OPLS-DA method (Orthogonal Partial Least Squares Discriminant Analysis), these two different kinds freshwater fish under different states were completely discriminated. The metabolites changes in digested fish soups could reveal the information of chemical compounds which play important roles in the body. Furthermore, the metabolic patterns of different kinds of fish soups could reflect the various nutrition profiling characteristics for dietary therapy.

Tinnitus is a debilitating auditory disorder commonly described as a ringing in the ears in the absence of an external sound source. Although various risk factors have been reported to be related to the perception of tinnitus, sound trauma is considered the primary cause. Neuronal hyperactivity is one of the potential mechanisms for the genesis of tinnitus and has been identified within major regions of the central auditory system, including the cochlear nucleus (CN) and the auditory cortex (AC). An imbalance of excitatory and inhibitory neu-rotransmission has been attributed to this hyperactivity. However, no study has directly cor-related tinnitus with the extracellular levels of amino acids in the CN and the AC using mi-crodialysis, which reflects the functions of these neurochemicals. In the present study, rats were exposed to either a sham condition or acoustic trauma and then subjected to behavioral confirmation of tinnitus after one month. They were further divided into sham (aged n=6; young n=6), tinnitus-positive (aged n=7; young n=7), and tinnitus-negative (aged n=3; young n=3) groups. In vivo microdialysis was utilized to collect samples from the CN and the AC simultaneously in the same rat. Extracellular levels of amino acids were quantified using high-performance liquid chromatography (HPLC) coupled with an electrochemical detector (ECD). The effects of sound stimulation and age on neurochemical changes associ-ated with tinnitus were also examined. It was found that there were no significant differ-ences in either the basal levels or the sound stimulation-evoked changes of any of the amino acids examined in the CN and the AC, between sham and tinnitus animals. However, the ba-sal levels of serine and threonine exhibited age-related alterations in the AC and significant differences in threonine and glycine levels were observed in the responses to 4 kHz and 16 kHz stimuli in the CN. These results demonstrated a lack of a direct link between extracellu-lar levels of amino acids in the CN and the AC and tinnitus perception in a rat model of tin-nitus. Further studies investigating a wide range of neurochemicals in both auditory and non-auditory brain regions are needed in order to understand tinnitus-related changes in neuro-transmission.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

This narrative review synthesizes findings from empirical studies to explore the factors influencing the adoption of ChatGPT in higher education. The review highlights several critical determinants, both confirmed and debatable, of ChatGPT acceptance among students and educators. Previous studies have predominantly utilized theories such as the Technology Acceptance Model (TAM), the Unified Theory of Acceptance and Use of Technology (UTAUT), and the Diffusion of Innovations (DoI) theory. Confirmed factors include performance expectancy, effort expectancy, social influence, facilitating conditions, and trust, which significantly predict user attitudes and intentions toward adopting ChatGPT. Perceived usefulness and ease of use are core components influencing adoption positively. However, some factors have shown inconsistent impacts. While generally critical, effort expectancy and facilitating conditions vary based on context. Social influence, demographic characteristics (age, gender), extrinsic motivation, and technology readiness exhibit inconsistent effects, suggesting that intrinsic motivations may be more critical. Data collection primarily used online surveys with structured questionnaires, varying widely in sample sizes from small pilot studies to large-scale surveys and covering diverse academic disciplines. Practical implications suggest enhancing perceived usefulness and ease of use through training and technical support, building trust by addressing privacy concerns, and leveraging social influence to drive adoption. The review underscores the need to refine technology acceptance models to incorporate broader psychological and contextual factors, integrate intrinsic motivation theories, and adopt a systems thinking approach. Addressing limitations such as potential selection bias and the quality and scope of existing studies, future research can develop robust models and provide deeper insights into ChatGPT adoption dynamics in higher education, supporting its effective integration to enhance learning outcomes and foster educational innovation.

Acemella oleracea is known as toothache plant belongs to the family of Asteraceae. It is treated as a medicinal remedy like tuberculosis, illness, cough, rheumatism, and illness. This study was concentrated on the antioxidant, cytotoxic, antimicrobial & thrombolytic activities of methanol extract of Acmella oleracea leaves using in vitro model. The antioxidant activity was estimated as trolox equivalent antioxidant capacity utilizing the DPPH and reducing power tests. The plant extract was tested for its cytotoxic action using a brine shrimp lethality bioassay, thrombolytic activity using clot disruption, and antibacterial activity using a disc diffusion assay technique against four distinct gram-positive and gram-negative bacteria. IC₅₀ value of standard ascorbic acid for DPPH was 7.8µg/ml and the IC50 of the methanol extract of Acmella oleracea leaves was 198.34µg/ml that was moderate effect at all compare with ascorbic acid. Thrombolytic assay of Streptokinase as a positive control showed 88.49% where the extract shows 18.69% lytic activity shows the assay. In this study, the sample of LC₅₀ results of cytotoxicity assay was 1.431 µg/mL which can be treated as less activity. Moreover, the extracts showed low to moderate antibacterial activity against both gram-negative and gram-positive bacterial stains (zone of inhibition-10-26 mm). Vibrio Mimicus bacteria stains exhibited the highest level of activity, with a range of 23 for the diameter of the growth inhibition zone. The current review shows leaf extracts of Acmella oleracea may be used as a source of antioxidant and thrombolytic activity, as well as a significant source of antibacterial and anticancer substances. Further research is required to evaluate in-vivo the pharmacological activity of Acmella oleracea leaves in order to identify the essential metabolites and potential mechanisms.

The poor success rate of preclinical drugs which target the nervous system is related to the highly complex nature of brain physiology and pathophysiology. For in vitro drug screening in this field, the two-dimensional (2D) approach - where cells are incubated in a monolayer - is not physiologically relevant. In contrast, in vivo rodent models are very low throughput and expensive. As such, improved, well-characterised three dimensional (3D) in vitro models should be employed to bridge the gap between 2D in vitro primary screening and rodent models by incorporating aspects of the in vivo brain environment. These key features include the extracellular matrix (ECM) and a multidimensional relationship of supporting cells. In this study, a neural progenitor cell line was differentiated into the main types of cells found in brain, including neurons and astrocytes. This model was designed in a 3D extracellular matrix replacement in a minimalised manner. Different culture formats using multi-well plates were explored and a high-throughput cellular imaging platform was applied. Next, we applied this model to assess neural toxicity of a newly synthesised dual-specificity tyrosine-regulated kinase 1 (DYRK1) inhibitor derived from natural compounds, which is structurally related to a natural DYRK1A inhibitor harmine, K04179. Chemical studies have already shown that K04179 has higher specificity to DYRK1A compared with previously reported DYRK1 inhibitors, such as INDY. We have produced the first report of the biological effects of this new compound on the new 3D minimalised mid-brain model with quantification of both neuronal and astrocyte populations in tandem, revealing differential toxic effects of DYRK1 inhibitor compounds K04179 and INDY on neurons and glia.

Background: The mechanisms underlying the effect of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein con-vertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9 and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Methods: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Levels of E2, pro-protein convertase subtilisin/kexin type 9 (PCSK9), total cholesterol (TCHOL), high-density lip-oprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). Results: A total of 34 consecutive healthy women aged 38 (26-46) years old who underwent a full IVF cycle were included. E2 levels increased by 329.6% from E2min to E2max (108 [47-346] to 464 [241-2471] pg/mL, p<0.05). At the same time, serum PCSK9 levels significantly decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p<0.05). No significant changes in TCHOL, LDL-C, TGs and HDL-C were found (-0.4%, -3.8%, -2.2%, and +5.3%, p >0.05). Conclusions: The increase in endogenous E2 production during an IVF cycle was associated with a significant decrease in serum PCSK9 levels during a 7-day period.

For over a decade, endoscopic hemostatic powders have been used to manage upper gastrointestinal bleeding (UGIB). Various preclinical benchtop and animal models have been developed to evaluate these devices. Multiple companies have released hemostatic powders to market, assessing their safety and efficacy using an established porcine gastric vessel bleed model. This model simulates an aggressive arterial bleed, allowing prototypes to be tested under challenging conditions. It requires a surgeon to insert an artery segment into the gastric lumen and puncture it to produce a bleed. In our study, we tested a control group not included in prior research. We aimed to evaluate the relationship between intragastric pressure and bleed severity by injecting gas used to deliver hemostatic powder to the bleed site, without administering hemostatic powder. Our results indicate that elevated intragastric pressures alone can cause bleed cessation. Additional findings suggest that other factors in the model can lead to false positive hemostasis. This study highlights flaws in the porcine gastric vessel bleed model and underscores the need to develop more robust models for testing hemostatic devices, as no valid endoscopic bleed model currently exists. These experiments stress the importance of vetting preclinical models before acquiring efficacy data.

The aim of this article is to present the course of the COVID-19 pandemic in Poland in 2020-2022, the formation of ad hoc health and anti-crisis policies, an assessment of crisis management and the perceived impact of the pandemic and anti-crisis measures.The paper draws on literature, official reports on the pandemic, data from Eurostat and other information from state institutions and public organisations.Particular attention was paid to the analysis and evaluation of the objectives, instruments and effects of the policies pursued by the state in a coordinated manner, i.e. the anti-pandemic policy and the anti-crisis policy. The anti-pandemic policy in Poland has failed to protect the country from significant personal losses and negative impacts on the health of the population and demographic processes.The anti-crisis policy of the state carried out with the mobilisation of businesses and disciplined society, in the form of anti-crisis shields supplemented and adjusted on an ongoing basis, allowed Poland to avoid a deep crisis and economic recession. Attention was drawn to the need to coordinate the management of health and economic crises nationally and internationally, and to the need to have a medium-term anti-crisis state strategy and a system for the early detection of crisis symptoms.

Inhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate mode of action of pollutants. Gilian 3500 pumps equipped with Standard Midget Impingers were used to collect the airborne particulate from woodworking and metalworking environments. EpiAirway™ tissues were used to model half working day (4 h), full working day (8 h), and 3 working day exposures to occupational pollutants. Tissue viability was assessed using MTT assay. RT-qPCR analyses performed to analyze the expression of gelsolin, caspase-3, and IL-6. Tissue morphology was assessed by hematoxylin/eosin staining. Acute exposure to workspace pollutants slightly affected tissue viability and did not change the morphology. Both types of particles suppressed expression of gelsolin, with metalworking samples showing the most pronounced effect. A slight reduction in caspase-3 expression was observed. Particles from metalworking suppressed IL-6 expression. 3D Epithelial tissues can be used to model exposures to airborne pollutants. Exposure to particles from woodworking and metalworking had a minor effect on tissue viability but affected the expression of inflammation and apoptosis-related genes.