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Background: Snake venoms are mainly composed of a mixture of proteins and peptides with antiviral activity against several viruses including HIV. Therefore, snake venoms represent promising source for new antiviral drugs. Aim: The study examines the toxin's capacity to disrupt the spike glycoprotein of HIV, the virus accountable for the HIV epidemic. Methods: The active protein structure of HIV and snake toxins was derived from the protein RCSB-PDB. The interactions between this toxin and the spike protein were evaluated using molecular docking software/interface such as 'Cluspro 2' and analyzers such as 'PyMOL' and 'Ligplot'. The objective was to identify potential pharmacophores that could be used as a basis for future drug development. Results: The latest study findings uncover fascinating affinities and interaction patterns between snake poisons and the HIV spike glycoprotein. We analyzed the consequences of these interactions and their capacity to impair viral entry and infection. Conclusion: This work highlights a prospective approach for the advancement of antiviral treatments, utilizing nature's collection of toxins as a basis for pharmacophore-based medication exploration against viral infections. [Open Vet J 2024; 14(11.000): 2936-2949]

Ginger rich in polyphenols, possesses various biomedical properties. Researchers investigated the effects of dietary ginger supplementation on turkey performance traits, biochemical parameters, haematological parameters and mRNA gene expression. Ginger root powder was administered at different doses (0, 10, 20 and 40 g/kg) to the turkeys. Notably, the 20 g/kg group exhibited improved performance traits and a higher broiler production efficiency factor (BPEF). Importantly, ginger was found to be safe for turkeys based on serum indices. Furthermore, the expression of several growth-related genes, including growth hormone receptor (GHR), insulin-like growth factor 1 (IGF-1), adenine nucleotide translocase (ANT), cyclooxygenase 3 (COX-3) and uncoupling protein 3 (UCP-3), was upregulated in the 20 g/kg enhancing their growth performance and economic efficiency in addition to keeping their health status safe. Therefore, Ginger root powder can be supplemented for turkey at a concentration of 2% as the addition of ginger powder is a long-term process.

Purpose The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries.Methods Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days.Results Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p

ABSTRACT: Live vaccines containing Eimeria oocysts are commercially available to protect against avian coccidiosis. Additionally, probiotics (PRO) and prebiotics (PRE) improve the poultry productivity and health and can be used as anticoccidial substitutes. However, the impact of PRO and PRE on reproductive potential, lesion score, intestinal health, and immunization outcomes of the live coccidia vaccines has not received adequate attention. Five groups of unsexed 1-day-old broiler chicks were used as follows: negative control (NC); challenged control (CC); vaccinated and challenged (VC); vaccinated, PRO-treated, and challenged (V-PRO); and vaccinated, PRE-treated, and challenged (V-PRE). At 21 d post-vaccination (pv), the vaccine increased the count of cecal anaerobes (P ≤ 0.05) and coliforms (P > 0.05) as well as harmed body weight gain (WG) (P ≤ 0.05), cecal lactic acid bacteria (P ≤ 0.05), and plasma carotenoid level (P > 0.05). None of the additives decreased oocyst shedding after vaccination, although they lowered the middle intestine and cecal lesion scores (P > 0.05). Compared to VC (2.68 ± 0.12) and V-PRE (2.66 ± 0.05), the V-PRO group showed an improved carotenoid level pv (2.96 ± 0.05) (P ≤ 0.05). V-PRE exhibited higher WG (822.95 ± 18.25) (P > 0.05) and FI (1153.01 ± 10.02) (P ≤ 0.05) than VC (781.86 ± 25.16 and 1109.85 ± 33.68) and V-PRO pv (787.61 ± 19.92 and 1077.43 ± 15.99). Following the homologous coccidia challenge, coccidia-vaccinated broilers adminstered the PRO or PRE continued to exhibit protection levels comparable to those received the vaccine alone. During 2 weeks post-challenge, VC, V-PRO and V-PRE improved bird performance and reduced oocyst shedding and lesion scores compared to CC. Ultimately, PRO and PRE treatments did not significantly reverse the reduction in growth performance in broiler chickens vaccinated against coccidia during the 1st three weeks of age.

Quercetin (QRT), a potent flavonoid, holds immense mechanistic potential in enhancing various aspects of broiler chicken physiological status. This comprehensive study explores the profound еffеcts of QRT on behavior, productive performance, and immune functions, unraveling the underlying mechanisms behind its efficacy. Four hundred, one-day-old Cobb 500 chicks were placed randomly into 4 supplementation groups (100 birds /group and five replicates) and provided diets enriched with varying concentrations of QRT (0, 200, 400, and 600 ppm) for six weeks. Visual scanning revealed significant (P > 0.05) improvements in feeding and body care behaviors, accompanied by reduced instances of idleness and walking in the QRT-supplemented groups. Moreover, QRT supplementation exerted a substantial (P > 0.05) positive influence on weight gain, feed intake and the final body weight of the broilers. In-depth evaluation of immune parameters, QRT supplementation elicited significant (P > 0.05) enhancements in immune functions, including improved spleen, thymus, and bursa indices, enhanced secretion of immunoglobulin M (IgM) and immunoglobulin A (IgA), and stimulated humoral immunity against sheep red blood cells (SRBCs). Furthermore, QRT displays potent antioxidant properties, as showed by diminished splenic malondialdehyde levels and augmented activity of antioxidative stress enzymes. Remarkably, QRT supplementation elicited dose-dependent upregulation (P < 0.001) of key immune-related genes, such as intеrlеukin-4 (IL-4), interferon-γ (INF-γ), Toll-like receptor 2 (TLR2), and tumor necrosis factor-α (TNF-α) in the splenic tissue. Collectively, these mechanistic insights underscore the profound impact of QRT as a functional feed additive, fostering enhanced behavior, performance, and immune function in broiler chickens, while delivering robust antioxidant fortification.

5-Fluorouracil (5-FU) is one of the most used anticancer drugs. However, its nephrotoxicity-associated drawback is of clinical concern. Lycopene (LYC) is a red carotenoid with remarkable anti-inflammatory and anti-oxidative properties. In this study, rats were divided randomly into five groups: control, lycopene (10 mg) (10 mg/kg/day; P.O), 5-FU (30 mg/kg/day; i.p.), Lycopene (5 mg) + 5-FU (5 mg/kg + 30 mg/kg/day), and lycopene (10 mg) + 5-FU (10 mg/kg + 30 mg/kg/day). LYC attenuated the loss of renal function induced by 5-FU in a dose-dependent manner. Rats co-treated with LYC had lower serum urea, creatinine, uric acid and KIM-1 levels, and a higher serum albumin level than those receiving 5-FU alone. Furthermore, co-treatment with the high dose of LYC maintained renal oxidant–antioxidant balance by ameliorating/preventing the loss of antioxidants and the elevation of malondialdehyde. Rats treated with 5-FU had markedly lower renal levels of PPAR-gamma, HO-1, Nfr2, and Il-10 and higher levels of NF-kB, TNF-alpha, and IL6 compared to the control rats. Co-treatment with LYC attenuated the reduction in PPAR-gamma, HO-1, Nfr2, and IL-10 levels and moderated the elevated levels of NF-kB, TNF-alpha, and IL-6. The kidneys from rats co-treated with lycopene (10 mg) + 5-FU did not show the degenerative changes in the glomerular tufts and tubules observed for the rats treated with 5-FU alone. In conclusion, LYC is a promising therapeutic strategy for attenuating 5-FU-induced nephrotoxicity through the restoration of antioxidant activities and inhibition of inflammatory responses by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6, signals.

The present study aimed to characterize the biosurfactants synthesized by lactic acid bacteria (LAB) obtained from fermented foods, optimize the conditions for increasing the yield of biosurfactants and explore their antimicrobial and antibiofilm potential. Out of the 26 LAB isolates, isolate BS2 showed the highest biosurfactant production as indicated in the oil displacement test, drop collapse and emulsification activity. BS2 was identified as Lactiplantibacillus plantarum 1625 using 16S-rRNA gene sequencing and phylogenetic analysis. The biosurfactant produced by BS2 was identified as an anionic glycol-lipo-proteins by employing Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography–Mass Spectrometry (GC–MS) analysis. The biosurfactants produced by L. plantarum 1625 demonstrated strong antibacterial and antibiofilm characteristics against pathogenic strains such as Staphylococcus aureus MTCC 1049, Escherichia coli MTCC 1587, and Pseudomonas putida MTCC 1655. The minimal inhibition concentration value of antibacterial activity was found to be 0.1 mg/mL with the inhibition percentage ranging from 90 to 95%. Further, the effect of temperature, pH, and substrate composition on biosurfactant production was also studied to enhance it production using the Box–Behnken Design approach of Response surface methodology (RSM). Application of biosurfactant led to a considerable decrease in biofilm-forming harmful bacteria, as proven by scanning electron microscopy analysis. The results highlight the potential uses of biosurfactants in distinct industries, and biotechnological contexts, especially in the creation of new antimicrobial and antibiofilm agents.

Background: Lemongrass (LG) had various phytochemical components such as saponins, phenols, resins, alkaloids, tannins, flavonoids, glycosides and terpenes, minerals as well as vitamin C which had various pharmacological actions (antioxidant, anti-inflammatory, antibacterial, antibiotic, and antifungal) and growth promoter. The use of LG in broiler nutrition can be optimized the bird performance and gut health. Based on the high nutrition value of LG and absence of sufficient studies on the effect of lemongrass aqueous extract (LGX) on broiler performance and gut health (antioxidant and immune biomarkers and intestinal morphology), the aim of the present study is to investigate the impact of using LGX on productive performance, blood biomarkers, immunity and gut health of broilers. Methods: A total of two hundreds one-day- old male broiler chicks (Cobb 500) were fed on the starter basal diet for 6 days. From day 7 of age onwards, the birds were distributed, at random, into 4 groups. Each group included 5 replicates with 10 chicks per replicate. The birds in group 1 were not administered lemongrass extract (control, LGX0) while chicks in group 2 (LGX100), 3 (LGX200) and 4 (LGX300) were administered the aqueous extract of lemongrass in drinking water at levels of 100, 200 and 300 ml/l, respectively. The experimental period lasted for 35 day. Growth performance parameters, economic efficiency, hematological and biochemical biomarkers, expression of some antioxidant and immune related genes, cecal bacterial counts and intestinal morphological changes all were assessed. Results: The results indicated that, administration of LGX in drinking water at levels of 200, 100 ml/l, respectively significantly improved (p ≤ 0.001) body weight (BW), body weight gain (BWG) and feed conversion ratio (FCR) than the control but without any effect on economic efficiency index (EEI) and feed intake (FI). On the other hand, the addition of LGX in drinking water at levels of 300 ml/l significantly decreased (p ≤ 0.001) FI, EEI and all growth performance parameters as compared to those other groups. LGX supplemented birds groups exhibited higher Hb, PCV, MCH, platelets, and lymphocytes than the control group. However, the ratio of H/L in LGX100 and LGX200 groups was lower (p ≤ 0.001) than other groups. LGX supplemented groups showed low (p ≤ 0.001) cholesterol, creatinine, MDA and high (p ≤ 0.01) TAC. Up regulation (p ≤ 0.001) of the expressions of catalase, GPX1, and SOD1 were in LGX200 group compared to other groups. While, the proinflammatory genes expression (IL1B, IL6, IFNᵧ, and TNF) were down regulated (p ≤ 0.001) in the LGX200 compared to others. Moreover, LGX200 and LGX300 reduced (p ≤ 0.001) the intestinal pathogens counts (E.coli and Salmonella). Administration of LGX at levels of 200 and 100 ml/l, respectively enhanced (p ≤ 0.001) villi height and crypts depth. Conclusions: It was concluded that lemongrass aqueous extract can be included at level 100 and 200 ml/l in broilersˈ drinking water since it resulted in improved weight, feed conversion ratio, blood parameters, immunity and gut health without any deleterious effect on the health and performance of the birds. LGX at a 200 ml/l supplementation level achieved the best results followed by a 100 ml/l level. Also, the tested supplements can be used as natural growth promoter instead of antibiotic and help in solving the global problem of antimicrobial resistant bacterial strains responsible for human and animal diseases.

Abstract The present study aimed to investigate the decolorization of various commercial dyes by azoreductases (AzrBmH21, AzrBmH22/3, and AzrBmH24/5) through bioinformatics means, comprising molecular docking, molecular dynamics simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA). Therefore, four commercial dyes, namely acid orange 7, cresol red, methylene blue, and malachite green, were selected as potential targets for degradation by the above said azoreductases derived from Bacillus megaterium H2. The prediction of ligand binding or catalytic sites for AzrBmH21, AzrBmH22/3, and AzrBmH24/5 were performed using a machine learning algorithm based on the Prank Web and DeepSite chemoinformatic tool. This analysis revealed that several amino acids of AzrBmH2 interacted with the tested dyes, indicating the presence of distinct ligand-binding sites for AzrBmH2-dye complexes. Likewise, the binding affinity for AzrBmH21, AzrBmH22/3, and AzrBmH24/5 ranged from − 9.4 to − 5.5 kcal/mol, − 9.2 to − 5.4 kcal/mol, and − 9.0 to − 5.4 kcal/mol, respectively, with each complex stabilized at a minimum of 0–5 hydrogen bonds. MD simulations revealed stable AzrBmH2-dye complexes with RMSD and RMSF values ranging from 0.15 to 0.42 nm and 0.05 to 0.48 nm, respectively, with Rg values between 1.75 and 1.88 nm. MM-PBSA calculations indicated that the AzrBmH2–dye complexes, except for AzrBmH2–malachite green, exhibited the lowest binding energy (− 191.05 ± 7.08 to 314.19 ± 6.88 kcal/mol), with prevalent hydrophobic interactions (− 268.25 ± 12.25 to − 418.92 ± 29.45 kcal/mol) through van der Waals forces. Therefore, this study was able to highlight the potential role of enzymes, specifically azoreductases from Bacillus megaterium H2, in predicting the decolorization of commercial dyes. These findings could contribute to our understanding of the azoreductases’ mechanisms in bioremediation and for biotechnological applications.

This study aimed to evaluate the effect of adding liquid extract of algae (Hypnea musciformis, Grateloupia acuminata, and Sargassum muticum) (HGS) and Magnesium oxide nanoparticles (MgO NPs) using this extract to rear water of Oreochromis niloticus, on improving culture water indices, growth performance, digestive enzyme, hemato-biochemical characters, immune, antioxidative responses, and resistance after challenged by Aeromonas hydrophila with specific refer to the potential role of the mixture in vitro as resistance against three strains bacteria (Aeromonas sobria, Pseudomonas fluorescens, P. aeruginosa) and one parasite (Cichlidogyrus tilapia). The first group represented control, HGS0, whereas the other group, HGS5, HGS10, and HGS15 mL−1 of liquid extract, as well as all groups with 7.5 μg mL−1 MgO-NPs added to culture water of O. niloticus, for 60 days. Data showed that increasing levels at HGS 10 and HGS15 mL−1 in to-culture water significantly enhanced growth-stimulating digestive enzyme activity and a significantly improved survival rate of O. niloticus after being challenged with A. hydrophila than in the control group. The total viability, coliform, fecal coliform count, and heavy metal in muscle partially decreased at HGS 10 and HGS15 mL−1 than in the control group. Correspondingly, the highest positive effect on hemato-biochemical indices was noticed at levels HGS 10 and HGS15 mL−1. Fish noticed an improvement in immune and antioxidant indices compared to control groups partially at HGS 10 and HGS15 mL−1. Interestingly, fish cultured in rearing water with the mixture provided downregulated the related inflammatory genes (HSP70, TNF, IL-1β, and IL-8) partially at HGS15 mL−1. In vitro, the mixture showed positive efficiency as an antibacterial and partially antiparasitic at HGS 10 and HGS15 mL−1. This study proposes utilizing a mixture of (HGS) and (MgO-NPs) with optimum levels of 10–15 mL-1 in cultured water to improve water indices, growth, health status, and increased resistance of O. niloticus against bacterial and parasitic infection.

Background: Venomous marine cone snails produce unique neurotoxins called conopeptides or conotoxins, which are valuable for research and drug discovery. Characterizing Conus venom is important, especially for poorly studied species, as these tiny and steady molecules have considerable potential as research tools for detecting new pharmacological applications. In this study, a worm-hunting cone snail, Conus flavidus inhabiting the Red Sea coast were collected, dissected and the venom gland extraction was subjected to proteomic analysis to define the venom composition, and confirm the functional structure of conopeptides. Results: Analysis of C. flavidus venom identified 117 peptide fragments and assorted them to conotoxin precursors and non-conotoxin proteins. In this procedure, 65 conotoxin precursors were classified and identified to 16 conotoxin precursors and hormone superfamilies. In the venom of C. flavidus, the four conotoxin superfamilies T, A, O2, and M were the most abundant peptides, accounting for 75.8% of the total conotoxin diversity. Additionally, 19 non-conotoxin proteins were specified in the venom, as well as several potentially biologically active peptides with putative applications. Conclusion: Our research displayed that the structure of the C. flavidus-derived proteome is similar to other Conus species and includes toxins, ionic channel inhibitors, insulin-like peptides, and hyaluronidase. This study provides a foundation for discovering new conopeptides from C. flavidus venom for pharmaceutical use.

Physico-chemical properties of fish flesh are reliable predictors of fillet quality and nutritional value. In our study, the age-related variations of the chemical composition, pH, water activity (aw), water holding capacity (WHC), color and texture analysis, protein thermal stability, myofibrillar fragmentation index (MFI), glycogen content, protein oxidation and protein profiles were investigated in Oncorhynchus mykiss (rainbow trout) fillet. The results revealed that protein denaturation temperatures (Tmax1 and Tmax2) decreased by 2 % and 11.6 % depending on fish age. Tmax1 and Tmax2 values in the same groups were raised 71 % at 11 months' fish and this increase was 58 % at 23 months’ fish. An age-related reduction by 66.6 % and 31.25 % was noticed for protein oxidation markers sulfhydryl groups and disulfide bonds. MFI value increased by 86.6 % connected with age.The characteristics of fish meat quality are complex and are influenced by various factors that affect the degree of freshness of the product and its acceptance in the market. Taking into account the different demands of the consumer, this study has shown that age at slaughter has an impact on final product quality and that the recommended age at slaughter, taking into account market weight, positively affects meat quality.

This study sheds the light on the potential of licorice (Glycyrrhiza glabra) root aqueous extract as a cornerstone for mitigating and detoxifying the residues of the widely used agricultural Glyphosate-based pesticides (GBPs). This study examined the GBPs toxic effects on kidney, liver, thyroid functions, and apoptosis using 50 adult male albino rats. All rats were divided into 5 groups, with 10 each. Control: served as untreated rats. GBP: rats were treated with 1 mL glyphosate solution 24 % orally for three weeks. The glyphosate-treated rats were gavaged with licorice root aqueous extractsolution (100, 200, and 300 mg/mLdistilled water, respectively) daily for three weeks. Licorice root aqueous extract solution (300 mg/mL distilled water) yielded notable reductions in liver, kidney enzymes, albumin, and AFP levels within the serum. Immunological tests, including immunohistochemical evaluations of caspase-3 and TNF-α expressions revealed a dose-dependent attenuation of apoptosis and inflammation with licorice intervention. This will provide a valuable perspective for agricultural practices future and paving the way for a more sustainable approach for using GBPs in animal agriculture industries.

Abstract Objectives Pseudomonas aeruginosa (P. aeruginosa) is one of the most serious pathogens implicated in antimicrobial resistance, and it has been identified as an ESKAPE along with other extremely significant multidrug resistance pathogens. The present study was carried out to explore prevalence, antibiotic susceptibility phenotypes, virulence-associated genes, integron (int1), colistin (mcr-1), and β-lactamase resistance' genes (ESBls), as well as biofilm profiling of P. aeruginosa isolated from broiler chicks and dead in-shell chicks. Design A total of 300 samples from broiler chicks (n = 200) and dead in-shell chicks (n = 100) collected from different farms and hatcheries located at Mansoura, Dakahlia Governorate, Egypt were included in this study. Bacteriological examination was performed by cultivation of the samples on the surface of both Cetrimide and MacConkey’s agar. Presumptive colonies were then subjected to biochemical tests and Polymerase Chain Reaction (PCR) targeting 16S rRNA. The recovered isolates were tested for the presence of three selected virulence-associated genes (lasB, toxA, and exoS). Furthermore, the retrieved isolates were subjected to phenotypic antimicrobial susceptibility testing by Kirby–Bauer disc diffusion method as well as phenotypic detection of ESBLs by both Double Disc Synergy Test (DDST) and the Phenotypic Confirmatory Disc Diffusion Test (PCDDT). P. aeruginosa isolates were then tested for the presence of antibiotic resistance genes (ARGs): int1, mcr-1, and ESBL genes (OXA-10, OXA-2, VEB-1, SHV, TEM, and CTX-M). Additionally, biofilm production was examined by the Tube Adherent method (TA) and Microtiter Plate assay (MTP). Results Fifty –five isolates were confirmed to be P. aeruginosa, including 35 isolates from broiler chicks and 20 isolates from dead in-shell chicks. The three tested virulence genes (lasB, toxA, and exoS) were detected in all isolates. Antibiogram results showed complete resistance against penicillin, amoxicillin, ceftriaxone, ceftazidime, streptomycin, erythromycin, spectinomycin, and doxycycline, while a higher sensitivity was observed against meropenem, imipenem, colistin sulfate, ciprofloxacin, and gentamicin. ESBL production was confirmed in 12 (21.8%) and 15 (27.3%) isolates by DDST and PCDDT, respectively. Antibiotic resistance genes (ARGs): int1, mcr-1, and ESBL genes (OXA-10, SHV, TEM, and CTX-M), were detected in 87.3%, 18.2%, 16.4%, 69.1%, 72.7%, and 54.5% of the examined isolates respectively, whereas no isolate harbored the OXA-2 or VEB-1 genes. Based on the results of both methods used for detection of biofilm formation, Kappa statistics [kappa 0.324] revealed a poor agreement between both methods. Conclusions the emergence of mcr-1 and its coexistence with other resistance genes such as β-lactamase genes, particularly bla OXA-10, for the first time in P. aeruginosa from young broiler chicks and dead in-shell chicks in Egypt pose a risk not only to the poultry industry but also to public health. Graphical Abstract

This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa (kiwifruits) aqueous extract in streptozotocin-treated rats. Animals were distributed into; control, A. deliciosa aqueous extract (ADAE; 1 g/kg orally), streptozotocin (STZ; 50 mg/kg, i.p, single dose), and STZ plus ADAE, respectively. Results showed that ADAE had high antioxidant and radical scavenging potency. Elevation in blood sugar level, lipid peroxidation (LPO), kidney function biomarkers, and perturbations in hematological parameters were observed in diabetic rats. While, enzymatic and non-enzymatic antioxidants, protein content, and alkaline phosphatase (ALP) activity declined. Furthermore, histological, immunohistochemical alpha-smooth muscle actin immunoreactivity (α-SMA-ir) and histochemical (collagen, total protein, DNA, and RNA) alterations were observed in rat kidneys. Moreover, STZ produced upregulation of inflammatory associated genes (tumor necrosis factor-alpha; TNF-α and transforming growth factor β1; TGF-β1) and triggered apoptosis by upregulating apoptotic related gene [Bcl2-associated X protein (Bax)] and downregulating anti-apoptotic related gene B-cell lymphoma-2 (Bcl-2) based on real-time PCR data. Moreover, diabetic rats administered with ADAE showed significant restoration in LPO, antioxidant status, and biochemical indices besides tissue architecture, and genes improvement regarding STZ group. Conclusively, A. deliciosa has a valuable ameliorative influence and can restore glucose levels and improve kidney dysfunction in diabetic rats.

Colorectal cancer is the second leading cause of cancer-related deaths. In 2018, there were an estimated 1.8 million cases, and this number is expected to increase to 2.2 million by 2030. Despite its prevalence, the current therapeutic option has a lot of side effects and limitations. Therefore, this study was designed to employ a computational approach for the identification of anti-cancer inhibitors against colorectal cancer using Resveratrol derivatives. Initially, the pass prediction spectrum of 50 derivatives was conducted and selected top seven compounds based on the maximum pass prediction score. After that, a comprehensive analysis, including Lipinski Rule, pharmacokinetics, ADMET profile study, molecular orbitals analysis, molecular docking, molecular dynamic simulations, and MM-PBSA binding free energy calculations. The reported binding affinity ranges of Resveratrol derivatives from molecular docking were -6.1 kcal/mol to -7.9 kcal/mol against the targeted receptor of human armadillo repeats domain of adenomatous polyposis coli (APC) (PDB ID: 3NMW). Specifically, our findings reported that two compounds [(03) Resveratrol 3-beta-mono-D-glucoside, and (29) Resveratrol 3-Glucoside] displayed the highest level of effectiveness compared to all other derivatives (-7.7 kcal/mol and -7.9 kcal/mol), and favorable drug-likeness, and exceptional safety profiles. Importantly, almost all the molecules were reported as free from toxic effects. Subsequently, molecular dynamic simulations conducted over 100ns confirmed the stability of the top two ligand-protein complexes. These findings suggest that Resveratrol derivatives may be effective drug candidate to manage the colorectal cancer. However, further experimental research, such as in vitro/in vivo studies, is essential to validate these computational findings and confirm their practical value.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer–Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent “n” was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

ABSTRACT: Investigating the impact of early egg production selection (the first 90 d of laying) on egg production features, cumulative selection response (CSR), and the mRNA expression of gonadotropins (FSHβ and LHβ), and their receptors (FSHR and LHR), in Japanese quails was the goal. The selection experiment involved 1293 females in all, 257 from the base group and 1036 from the 4 selected generations. Age and body weight at sexual maturity (ASM, BWSM), weight of the first egg (WFE), days to the first 10 eggs (DF10E), egg mass for the first 10 eggs (EMF10E), egg weight (EW), egg number at the first 90 d of laying (EN90D), and egg mass at the first 90 d of laying (EM90D) were all recorded. Most egg production traits had heritability estimates that were low to moderate and ranged from 0.17 to 0.33., where the highest estimates were reported for EN90D (0.33) and BWSM (0.32). With the exception of EN90D, low to moderate positive genetic correlations were observed between ASM and other egg production traits (0.17–0.44). The fourth generation showed significantly (P < 0.05) lower ASM and DF10E but higher BWSM, WFE, EN90D, EM10E, and EM90D when compared with the base generation. CSR were significant (P < 0.05) for ASM (−6.67 d), BWSM (27.13 g), WFE (0.93 g), DF10E (−1.25 d), EN90D (7.24 egg), EM10E (10.57 g), and EM90D (140.0 g). FSHβ, LHβ, FSHR, and LHR gene mRNA expression was considerably (P < 0.05) greater in the fourth generation compared to the base generation. In conclusion, selection programs depending on the efficiency of egg production (EN90D) could improve the genetic gain of egg production traits and upregulate the mRNA expression of FSHβ, LHβ, FSHR, and LHR genes in selected quails (fourth generation). These findings might help to enhance breeding plans and create commercial lines of high egg production Japanese quails.

Chlorpyrifos (CPS), an organophosphorus insecticide, is widely used for agricultural and non-agricultural purposes with hazardous health effects. Berberine (BBR) is a traditional Chinese medicine and a phytochemical with anti-inflammatory and anti-oxidative properties. The present study evaluated the effects of BBR against kidney damage induced by CPS and the underlying mechanisms. An initial study indicated that BBR 50 mg/kg was optimal under our experimental conditions. Then, 24 rats (6/group) were randomized into: control, BBR (50 mg/kg/day), CPS (10 mg/kg/day), and CPS + BBR. BBR was administration 1 h prior to CPS. Each treatment was delivered daily for a period of 28 consecutive days using a gastric gavage tube. Compared to CPS-alone treated rats, BBR effectively improved renal function by preventing the rise in serum urea, creatinine, and uric levels. The reno-protective effects of BBR were confirmed through a histological examination of kidney tissues. BBR restored oxidant-antioxidant balance in renal tissues mediated by Keap1/Nrf2/HO-1 axis modulation. In addition, BBR decreased nitric oxide (NO) and myeloperoxidase (MPO) activity. This was paralleled with the potent down-regulation of NF-κB. Furthermore, BBR exhibited anti-apoptotic activities supported by the upregulation of Bcl-2 and down-regulation of Bax and caspase-3 expression. In conclusion, our data suggest that BBR attenuates CPS-induced nephrotoxicity in rats by restoring oxidant-antioxidant balance and inhibiting inflammatory response and apoptosis in renal tissue. This is mediated, at least partly, by modulation of the Nrf2/HO-1 axis.

Abstract Sitotroga cerealella is one of the major pests of cereals in the field and storage conditions throughout the world. The main objective was to study the life tables of S. cerealella on wheat, maize and barley and its implications on percent parasitism of Trichogramma chilonis. S. cerealella is reared under lab conditions as its eggs are utilized for rearing T. chilonis. Fresh eggs of S. cerealella were collected and after hatching the neonate larvae of S. cerealella were transferred onto each host plant species for obtaining first (F1) generation (G). Seventy eggs were used for each host and each egg was used as a replicate. Daily observations were made for recording the life-table parameters of the S. cerealella. The data showed that the developmental time of S. cerealella eggs and pupae was maximum (5.68 and 7.75 days) when reared on wheat, while the maximum larval duration (19.77 days) of S. cerealella was recorded on barley. The maximum fecundity (290.30 ± 22.47 eggs/female) was recorded on maize, while minimum fecundity per female was recorded on barley (159.30 eggs/ female). The S. cerealella reared on maize had significantly higher values of finite rate of increase (λ), intrinsic rate of increase (r), and net reproductive rate (R o ) (0.14 ± 0.04 day− 1, 1.16 ± 0.05 day− 1, and 136.85 ± 20.25 eggs/ female) respectively. The mean generation time (T) (35.18 ± 0.61 days) was higher on wheat. Likewise, the gross reproductive rate (GRR) and the age-stage specific reproductive values (v xj ) of newly oviposited eggs of S. cerealella were recorded higher (136.85 ± 20.25; 1.160 offspring) on maize. The data regarding the efficacy of T. chilonis for different parameters were recorded higher on maize i.e., percent parasitism (89.00 ± 2.30%), percent adult emergence (81.60 ± 1.20%), adult longevity (3.80 ± 0.10 days) and total adult longevity (9.90 ± 0.20 days) as compared to wheat and barley. Our findings revealed that S. cerealella can be best reared on maize under laboratory conditions as it prefers this host as compared to wheat and barley. Therefore, assigning the most susceptible and favorite host (maize) would help us to improve T. chilonis mass production under laboratory conditions.

Abstract The current study regarding the effects of larval diets on the life table parameters of dengue mosquitoes, Aedes aegypti was conducted under laboratory conditions at 27 ± 2 °C and 60 ± 5% relative humidity at NIFA (Nuclear Institute for Food and Agriculture) Peshawar, Pakistan. The data on life table parameters of Ae. aegypti reared on Diet 1 (replacement diet), Diet 2 (Khan’s diet for Anopheles), Diet 3 (Khan’s modified diet) and Diet 4 (IAEA diet) were analyzed using the age-stage, two-sex life table software. Diet 4 (IAEA) was used as a control for comparison. The results indicated that significantly maximum percentage of egg hatching of Ae. aegypti was observed when reared on Diet 4 (73.86%) and Diet 3 (72.90%), while less % of egg hatching was recorded in Diet 1 (40.67%) and Diet 2 (55.53%). The data further showed that the Diet 3 had a highest intrinsic rate of increase (r) (0.097 ± 5.68 day−1), finite rate of increase (λ) (1.10 ± 6.26 day−1) and net reproductive rate (R 0 ) (11.99 ± 1.52 eggs/female) followed by Diet 2 and Diet 4. The mean generation time (T) of Ae. aegypti reared on Diet 3 (23.67 ± 0.86 days) and Diet 1 (24.05 ± 0.61 days) was significantly shorter than Diet 2 (26.15 ± 0.71 days) and Diet 4 (26.41 ± 0.38 days). The overall results revealed that Diet 3 showed good results at different life table parameters of Ae. aegypti and can be used as the preferred diet in the Sterile Insect Technique (SIT) where the mass culture of mosquitoes is required.

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg-1), PE-MPs (1.5 mgkg-1) + KFD (20 mgkg-1) co-treated and KFD (20 mgkg-1) only treated group. PE-MPs intoxication significantly (P

IntroductionThe research focuses on Rhododendron ferrugineum L., Nepal’s national flower and Uttarakhand’s state tree, thriving in high-altitude mountain ecosystems.Methodology and ResultA study conducted in Himachal Pradesh (Latitude: N 31° 6’ 2.0088”, Longitude: E 77° 10’ 29.9136”) identified leaf anomalies resembling rust-like manifestations in R. ferrugineum. These anomalies were traced back to the pathogenic fungus Curvularia tuberculata, marking the first documented case of its impact on R. ferrugineum in India.DiscussionThis discovery emphasizes the need for vigilant monitoring, disease management research, and conservation efforts to protect the cultural and ecological significance of this iconic shrub. Beyond its immediate findings, the study introduces a novel dimension to Indian flora by associating C. tuberculata with R. ferrugineum, historically linked to monocotyledonous crops. The research methodology combines traditional microscopic examination with advanced genomic sequencing and phylogenetic analysis, enhancing pathogen identification accuracy.Future prospectIn a broader context, this research aligns with the United Nations Sustainable Development Goals (SDGs) by highlighting the importance of environmental preservation, conservation, and sustainable management. It underscores the intricate interplay between biodiversity, cultural heritage, and the need for holistic solutions. Overall, this study calls for proactive measures to protect R. ferrugineum’s cultural and ecological heritage and emphasizes the significance of interdisciplinary approaches in addressing emerging ecological threats.

Clindamycin phosphate is a topical antibiotic agent used to treat acne vulgaris, while Aloe vera has both antimicrobial and anti-inflammatory properties. The current study is aimed at formulating an antiacne gel with antioxidant and antimicrobial effects. The antiacne gels were prepared by using polymer HPMC K15M by cold dispersion method. Unveiling the intricacies of gel design, our research harnessed the power of Design Expert 11 to optimize critical parameters—viscosity, spreadability, and permeability. In vitro characterization tests, including pH, spreadability, viscosity, permeability, antimicrobial activity, antioxidant activity, and stability of the gels, were performed. The results of in vitro characterization tests showed that the gels had a mint-like odor, a pH of 6.8, and a spreadability of 21.5 g cm/sec. The gels had a viscosity of 34.2 Pa s and drug content ranging within 90%-110%, as per USP standards. Notably, in vitro permeation assays reveal an exceptional 86% drug release, showcasing the efficacy of our formulation. The uniqueness of our study lies not only in the robust optimization process but also in the multifaceted characterization. Our gel emerges as a promising candidate, exhibiting not only desired antimicrobial and antioxidant properties against acne vulgaris but also demonstrating stability under varied conditions. As we advance toward in vivo studies, our research paves the way for a nuanced understanding of the safety and efficacy of this distinctive antiacne gel.

Diabetes-related distress (DRD) is a psychological syndrome with worsened prognosis in uncontrolled diabetic patients. The current study aimed to assess the factors contributing to DRD among the Lebanese population using the Diabetes Distress Scale (DDS-17) score and its sub-scores. A cross-sectional analysis was conducted between March and September 2021 enrolling. 125 diabetic from six Lebanese governorates through an online survey. The survey included two parts: the first section gathered sociodemographic data sociodemographic and socioeconomic data and the second one focused on assessing the Diabetes Distress Scale (DDS-17) score. Participants 30 years old and above had higher emotional distress compared to younger patients, (65.2 % versus 45.5 %). Those with a primary educational level showed significantly higher emotional distress than those with a secondary and tertiary level of education (72.5 %, versus 66.7 % and 46.4 %). Participants who were treated with both insulin and non-insulin medications or had a diastolic blood pressure of more than 90 mmHg showed significantly moderate to high distress (63.6 % or 53.8 %). Participants who lived in rural areas showed higher distress (35.6 %). Obese and overweight had significant moderate to high distress (64.1 %, and 48.0 %). The same results were found in non-married (divorced or widowed) and married participants (76.9 % and 51.3 %). The association between medical history with total distress showed that participants with glycemic store HbA1c of more than 6.5 followed by those who had HbA1c between 5.7 and 6.4 showed moderate to high total distress (45.9 % and 40.0 %). It is concluded that the prevalence of DRD is high in Lebanon, more common among rural residents, and among participants high HbA1c, low educational level, unmarried and on complex treatment regimens. Screening for DRD and providing better support can optimize clinical outcomes.

Aflatoxins (AFs) are secondary metabolites produced by the fungus Aspergillus flavus, of which Aflatoxin-B1 (AFB1) appears to be the most cancerogenic and of the highest toxicity. AFB1 causes serious effects on several organs including the liver. Morin is a flavonol that exists in many fruits and plants and has diverse biological properties including anticancer, anti-atherosclerotic, antioxidant, anti-inflammatory, immunomodulatory, and multi-organ protective activities. The present study aims to evaluate the potential protective effects of morin against acute AFB1-induced hepatic and cardiac toxicity in rats. Forty rats were divided into five groups (n = 8) as follows: control received the vehicle, morin was orally administered 30/mg/kg body weight (MRN30), the AFB1 was administered orally at a dose of 2.5 mg/kg, twice on days 12 and 14 of the experiment for the 3rd, 4th, and 5th groups., AFB1-MRN15 was orally given morin at a dose of 15 mg/kg body weight, and AFB1-MRN30 orally received morin at 30 mg/kg body weight. The results indicated a significant decrease in serum AST, ALP, LDH, GGT, CK, CK-MB, 8-OHdG, IL-1β, IL-6, TNF-a levels in MRN30 compared to AFB1, and AFB1-MRN15 groups. However, the results indicated non-significant differences in the serum levels between MRN30, control, and AFB1-MRN30 groups. Meanwhile, regarding the hepatic and cardiac parameters, there were significant differences in the levels of MDA, NO, GSH, GSH-Px, SOD, and CAT in MRN30 compared to AFB1, and AFB1-MRN15 groups, overall implying the protective effects of morin. To conclude, morin at a dose of 30 mg/kg b. wt. showed significant enhancements in acute AFB1-induced hepatic and cardiac toxicity in rats, which could play a role in limiting the public health hazards of AFs.

In an innovative approach to push the boundaries of antimicrobial and antioxidant strategies, we present the synthesis and characterization of a novel terpolymer derived from N-Phenyl-p-phenylenediamine and 2-aminopyrimidine with formaldehyde in the presence of dimethylformamide as a reaction medium through polycondensation technique. Leveraging this terpolymer as a ligand, we introduce an intriguing terpolymer-metal complex, created with Ni (II) metal ion. In our pursuit to validate the structure and properties of these substances, we performed meticulous characterizations using important spectral studies such as FTIR, electronic, and 1H NMR spectroscopy. This provided us with a unique fingerprint for the (N-Phenyl-p-phenylenediamine-2-aminopyrimidine-formaldehyde) terpolymeric ligand (PAF) and its metal complex. In addition, the molecular weights of PAF terpolymer were established using gel permeation chromatography.Upon investigation, PAF terpolymer and PAF-Ni complex exhibited impressive antimicrobial activity, tested by the disc-diffusion technique. Both demonstrated potency against a range of harmful bacterial and fungal strains, including Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger. In an extension to their biological applications, we evaluated the free radical scavenging activity of PAF terpolymer and PAF-Ni complex using the DPPH assay. The complex PAF-Ni showcased an enhanced scavenging activity 73.94% (IC50 = 17.58) compared to the ligand PAF 63.06% (IC50 = 27.61) at 100 μg/ml indicating its potential role in oxidative stress management.

Chlorpyrifos (CPF), is an organophosphate pesticide that is widely used for agricultural purposes. However, it has well-documented hepatotoxicity. Lycopene (LCP) is a plant-derived carotenoid with antioxidant and anti-inflammatory activities. The present work was designed to evaluate the potential hepatoprotective actions of LCP against CPF-induced hepatotoxicity in rats. Animals were assigned into five groups namely: Group I (Control), Group II (LCP), Group III (CPF), Group IV (CPF + LCP 5 mg/kg), and Group V (CPF + LCP 10 mg/kg). LCP offered protection as evidenced by inhibiting the rise in serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) induced by CPF. This was confirmed histologically as LCP-treated animals showed liver tissues with less proliferation of bile ducts and periductal fibrosis. LCP significantly prevented the rise in hepatic content of malondialdehyde (MDA), depletion of reduced glutathione (GSH), and exhaustion of glutathione-s-transferase (GST) and superoxide dismutase (SOD). Further, LCP significantly prevented hepatocyte death as it ameliorated the increase in Bax and the decrease in Bcl-2 expression induced by CPF in liver tissues as determined immunohistochemically. The observed protective effects of LCP were further confirmed by a significant enhancement in heme oxygenase-1 (HO-1) and NF-E2–related factor 2 (Nrf2) expression. In conclusion, LCP possesses protective effects against CPF-induced hepatotoxicity. These include antioxidation and activation of the Nrf2/HO-1 axis.

Furan (C4H4O) is a naturally occurring organic compound. It develops as a result of the thermal processing of food and stimulates critical impairments in male reproductive tract. Eriodictyol (Etyol) is a natural dietary flavonoid possessing diverse pharmacological potentials. The recent investigation was proposed to ascertain the ameliorative potential of eriodictyol against furan-instigated reproductive dysfunctions. Male rats (n = 48) were classified into 4 groups: untreated/control, furan (10 mg/kg), furan+ eriodictyol (10 mg/kg + 20 mg/kg) and eriodictyol (20 mg/kg). At the 56th day of the trial, the protective effects of eriodictyol were evaluated by assessing various parameters. Results of the study revealed that eriodictyol attenuated furan-induced testicular toxicity in the biochemical profile by increasing catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) along with glutathione reductase (GSR) activities, whereas reduced the reactive oxygen species (ROS) along with malondialdehyde (MDA) levels. It also restored the normal state of sperm motility, viability, the count of hypo-osmotic tail swelled sperm as well as epididymal sperm number along with reduced sperm anomalies (morphological) tail, mid-piece and head. Furthermore, it elevated the decreased levels of luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) as well steroidogenic enzymes (17β-HSD, StAR protein & 3β-HSD) and testicular anti-apoptotic marker (Bcl-2) expression, whereas, down-regulating apoptotic markers (Bax & Caspase-3) expression. Eriodictyol treatment also effectively mitigated the histopathological damages. The outcomes of the current study provide fundamental insights into the ameliorative potential of eriodictyol against furan-instigated testicular toxicity.

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington’s disease (HD).Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability.Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain’s motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD.Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

The use of gelatin and gelatin-blend polymers as environmentally safe polymers to synthesis electrospun nanofibers, has caused a revolution in the biomedical field. The development of efficient nanofibers has played a significant role in drug delivery, and for use in advanced scaffolds in regenerative medicine. Gelatin is an exceptional biopolymer, which is highly versatile, despite variations in the processing technology. The electrospinning process is an efficient technique for the manufacture of gelatin electrospun nanofibers (GNFs), as it is simple, efficient, and cost-effective. GNFs have higher porosity with large surface area and biocompatibility, despite that there are some drawbacks. These drawbacks include rapid degradation, poor mechanical strength, and complete dissolution, which limits the use of gelatin electrospun nanofibers in this form for biomedicine. Thus, these fibers need to be cross-linked, in order to control its solubility. This modification caused an improvement in the biological properties of GNFs, which made them suitable candidates for various biomedical applications, such as wound healing, drug delivery, bone regeneration, tubular scaffolding, skin, nerve, kidney, and cardiac tissue engineering. In this review an outline of electrospinning is shown with critical summary of literature evaluated with respect to the various applications of nanofibers-derived gelatin.

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignant cancer and the third most frequent cause of tumour-related mortality worldwide. Currently, several surgical and medical therapeutic strategies are available for HCCs; however, the interaction between neoplastic cells and non-neoplastic stromal cells within the tumour microenvironment (TME) results in strong therapeutic resistance of HCCs to conventional treatment. Therefore, the development of novel treatments is urgently needed to improve the survival of patients with HCC. The first step in developing efficient chemotherapeutic drugs is the establishment of an appropriate system for studying complex tumour culture and microenvironment interactions. Three-dimensional (3D) culture model might be a crucial bridge between in vivo and in vitro due to its ability to mimic the naturally complicated in vivo TME compared to conventional two-dimensional (2D) cultures. In this review, we shed light on various established 3D culture models of HCC and their role in the investigation of tumour-TME interactions and HCC-related therapeutic resistance. Graphical Abstract

Vitamin D, a secosteroid hormone, appears to have significant beneficial effects on various physiological systems, including the musculoskeletal system. Vitamin D assists in the regulation of numerous critical biological functions and physiological processes in humans, including inflammation, oxidative stress, and mitochondrial respiration, and is also linked to cardiac diseases. It is also reported that vitamin D plays a central role in molecular and cellular mechanisms, which reduce oxidative stress, and tissue damage and regulate cellular health. On the other side, hypovitaminosis D reduces mitochondrial activity and increases oxidative stress and inflammation in the body. Hypervitaminosis D increases the prevalence and severity of cellular damage. It has also been reported that vitamin D is involved in many functions of the reproductive system in human and critically play an important role in the reproductive tissues of women and men. Its role is very well defined, starting from female menarche to menopause, pregnancy, and lactation, and finally in male fertility. Hence, the appropriate amount of vitamin D is necessary to maintain the normal function of cell organelles. Based on recent studies, it is understood that vitamin D is involved in the biological activities of mitochondria in cells, especially in cardiomyocytes. In this review, we emphasized the role of vitamin D in mitochondrial respiration, which could significantly influence heart health and human reproduction.

Background Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer’s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer’s disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. Result In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex’s dynamic development. Conclusion As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.

Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1’s binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.

BackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19.MethodsWe conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations.ResultsThe comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation.ConclusionsThe presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.

Nardostachys jatamansi (D. Don) DC is a highly valued medicinal herb that has been used in traditional medicinal systems for its remedial effects. Owing to the over-exploitation and unethical trade of N. jatamansi, the accelerating global demand of herbal products from this plant cannot be satisfied by the conventional extraction approach. In view of the progressive demand and incredible biological potential of herb, the present research was designed to optimize various extraction parameters for microwave-assisted extraction (MAE). The extracts obtained from the traditional and green approach were also assessed for the recovery of secondary metabolites and anti-Alzheimer’s potential. Various parameters like microwave power, temperature, and time of irradiation were optimized for MAE using Box Behkhen Design (BBD) The scanning electron microscopy of different plant samples was also done to observe the effect of microwave radiations. Further, the metabolite profiling of different extracts was also done by gas chromatography-mass spectrometry (GC-MS) analysis. Also the different behavioral and biochemical parameters along with acetylcholinesterase (AChE) inhibitory potential were assessed to evaluate the anti-Alzheimer’s potential. Optimized parameters for MAE were found to be as microwave power 187.04 W, temperature 90°C, and irradiation time 20 min. The extract yield in MAE was significantly enhanced as compared to the conventional method. Also, the total phenolic content and total flavonoid content (TFC) were improved pointedly from 32.13 ± 0.55 to 72.83 ± 1.1 mg of GAE/g of extract and 21.7 ± 0.85 to 39.21 ± 0.7 mg of RUE/g of extract respectively. Later, the GC-MS analysis of various extracts confirmed the enhancement in the concentration of various sesquiterpenes like jatamansone, spirojatamol, valerenal, valeric acid, globulol, nootkatone and steroidal compounds such as sitosterol, ergosterol, stigmastanone, etc. in the optimized extract. A significant improvement in anti-Alzheimer’s potential was also observed owing to the better concentration of secondary metabolites in the optimized microwave extract. From the current findings, it could be concluded that the MAE could be a successful and green alternative for the extraction and recovery of secondary metabolites from the selected medicinal herb.

Groundwater contamination through potentially harmful metals (PHMs) is an environmental hazard in Pakistan with significant human health risk reports. The current research was conducted in Sheikhupura District, which is a major industrial site in Punjab, Pakistan. According to the Punjab Directorate of Industries in Pakistan, there are a total of 748 industries in this area. These industries produce a lot of waste and effluent, which contaminate the environment with harmful and toxic materials. Continuous irrigation with industrial effluent and sewage sludge may make groundwater sources vulnerable. Therefore, we collected 243 groundwater samples from community tube wells to investigate the groundwater quality cconcerning PHM contaminations in the study area. This research presents the values of pH, total dissolved solids (TDS), electrical conductivity (EC), and potentially harmful metals (PHMs) like arsenic (As), manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), nickel (Ni), and iron (Fe). PHMs such as As (91%), Mn (14%), Pb (97%), Fe (45%), Zn (15%), in these samples were beyond the permitted limit recommended by the world health organization (WHO). Principal component analysis (PCA) results with total variability of (60%) reveal that the groundwater sources of the study area are contaminated about 30.9, 31.3, and 37.6% of contaminations of groundwater sources of this study are resulted from geogenic sources, anthropogenic sources, or both geogenic and anthropogenic sources, respectively. Such sources may include rock-water interaction, mining actions, agricultural practices, domestic sewage, and industrial effluent in the study area. Saturation indices show that the aquifers of the study area are saturated with lead hydroxide, zinc hydroxide, and goethite minerals, indicating that these minerals have a vital role in the contamination of groundwater. Health risk assessment results predicted that the non-carcinogenic risk (HQ) values of PHMs were found within the permissible limit (

Summary Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA‐based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well‐tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off‐targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.

(1) Background: Diet and statins are commonly used to treat high cholesterol (CHOL) levels. (2) Aim: To compare adherence to Mediterranean diet (Med-D), orthorexia nervosa (ON), and musculoskeletal pain in individuals in treatment with statins metabolized by CYP3A4, not metabolized by CYP3A4 or red yeast rice (RYR, containing monacolin K: MON-K). (3) Methods: starting from 80 individuals, after the exclusion of those with other causes of possible pain, 56 individuals were selected and divided into three groups according to the type of statin (CYP3A4, NO-CYP3A4 and MON-K). Adherence to the Med-D was evaluated with the MEDScore and a sub-score was calculated for fruit and vegetables consumption (MEDScore-FV). ON and musculoskeletal pain were assessed with the ORTO-15 and with the Nordic Musculoskeletal questionnaires, respectively. A retrospective analysis of CHOL decrease after treatment was conducted. (4) Results: CHOL levels were lower in CYP3A4 and NO-CYP3A4 after treatment (182.4 ± 6.3 and 177.0 ± 7.8 mg/dL, respectively), compared with MON-K (204.2 ± 7.1 mg/dL, p < 0.05). MON-K and CYP3A4 groups had a high prevalence of reported knee pain (33.3% and 18.8%, respectively) than NO-CYP3A4 group (0%, p < 0.05). A high percentage of individuals in MON-K take supplements and nutraceuticals (87.5%), whereas MEDScore-FV was higher in CYP3A4 (9.4 ± 0.2) compared to NO-CYP3A4 (7.6 ± 0.5, p < 0.05). (5) Conclusions: This study suggests that individuals receiving treatment with statins and RYR should be monitored from the perspective of plant foods’ consumption and nutraceutical use, to prevent musculoskeletal pain.

This study aims to increase the aqueous solubility of ciprofloxacin (CPN) to improve oral bioavailability. This was carried out by formulating a stable formulation of the Self-Emulsifying Drug Delivery System (SEDDS) using various ratios of lipid/oil, surfactant, and co-surfactant. A pseudo-ternary phase diagram was designed to find an area of emulsification. Eight formulations (F1-CPN–F8-CPN) containing oleic acid oil, silicone oil, olive oil, castor oil, sunflower oil, myglol oil, polysorbate-80, polysorbate-20, PEO-200, PEO-400, PEO-600, and PG were formulated. The resultant SEDDS were subjected to thermodynamic study, size, and surface charge studies to improve preparation. Improved composition of SEDDS F5-CPN containing 40% oil, 60% polysorbate-80, and propylene glycol (Smix ratio 6: 1) were thermodynamically stable emulsions having droplet size 202.6 nm, charge surface -13.9 mV, and 0.226 polydispersity index (PDI). Fourier transform infra-red (FT-IR) studies revealed that the optimized formulation and drug showed no interactions. Scanning electron microscope tests showed the droplets have an even surface and spherical shape. It was observed that within 5 h, the concentration of released CPN from optimized formulations F5-CPN was 93%. F5-CPN also showed a higher antibacterial action against S. aurous than free CPN. It shows that F5-CPN is a better formulation with a good release and high antibacterial activity.

Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma.Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4.Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events.Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.

The ameliorative effects of Spirulina and Saccharomyces cerevisiae (S. cerevisiae) against fipronil toxicity in Nile tilapia fish were investigated. Fipronil is a kind of pesticide that is widely used in agriculture, thus this trial was conducted to evaluate the effect of fipronil on growth related parameters (final body weight, feed intake, weight gain, feed conversion ratio, specific growth rate, and protein efficiency ratio), hematology related parameters (RBCs, WBCs, hemoglobin, packed cell volume, and deferential leukocytic count), biochemistry related parameters (alanine aminotransferase, aspartate aminotransferase, total protein, albumin, urea, and creatinine), histopathology of liver, intestine, gills, and spleen, and gene expression of antioxidants, stress, inflammatory, apoptotic, and related to junction proteins genes as SOD and GPx, COX II, TNF-α, Casp-3, and Claudin-3, respectively, in Nile tilapia (Oreochromis niloticus). Four hundred and five Nile tilapia fish were distributed in a glass aquarium into nine groups according to the Spirulina and S. cerevisiae supplemented diets, with or without fipronil contaminated water. The classified groups are control, Sc: S. cerevisiae (4 g/Kg diet), Sp: Spirulina (1 g/100 g diet), Fb1: 0.0021 mg fipronil/L, ScFb1: S. cerevisiae (4 g/Kg diet) with 0.0021 mg fipronil/L, SpFb1: Spirulina (1 g/100 g diet) with 0.0021 mg fipronil/L, Fb2: 0.0042 mg fipronil/L, ScFb2: S. cerevisiae (4 g/Kg diet) with 0.0042 mg fipronil/L, and SpFb2: Spirulina (1 g/100 g diet) with 0.0042 mg fipronil/L. The results of the present investigation indicated the negative effect of fipronil on the growth performance parameters of Nile tilapia, which was confirmed by the results of hematology, biochemistry, and histopathology. In addition, the results of gene expression of antioxidants, stress, inflammatory, and apoptotic genes indicate the genotoxicity of fipronil. However, these negative effects were ameliorated by Spirulina and Saccharomyces dietary supplementation.

Osteoporosis (OP) is a serious health problem, and the most popular therapeutic strategy for OP is hormone replacement (estrogen); however, it increases the risk of reproductive cancers. Hydroxyapatite (HA) nanoparticles have a similar chemical structure to the bone mineral component and can be used as a new remedy for OP. This study was designed to investigate the osteoporosis-protective potential of nano zinc hydroxyapatite (ZnHA-NPs) and/or estradiol (E2) combined therapy. A total of 35 adult female rats were assigned into five groups (n = 7): 1) control group; 2) ovariectomized group (OVX); 3) OVX received oral estradiol replacement therapy (OVX/E2); 4) OVX received ZnHA replacement therapy (OVX/ZnHA); and 5) OVX received both estradiol and ZnHA-NPs combined therapy (OVX/E2+ZnHA). After 3 months of treatment, serum bone markers and estrogen level, oxidative/antioxidant, and inflammatory cytokines were determined. Additionally, femoral expression of estrogen receptors alpha and beta (ESR1; ESR2), receptor activator of nuclear factor-kappa B (RANKL) ligand, osteoprotegerin (OPG), bone mineral density (BMD), histological alterations, and immunohistochemical expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were assessed. ALP, PINP, Ca, and P concentrations improved significantly (p < 0.05) in all treatment groups, especially in the OVX/E + ZnHA group. MDA and NO were higher in OVX rats, while SOD activity and GSH were lower (p < 0.05). E2 alone or with ZnHA-NPs restored the estimated antioxidant molecules and cytokines toward normal levels in OVX rats (p < 0.05). On the other hand, E2 and ZnHA increased OPG and OC expression in femurs while decreasing ESR1, ESR2, and NF-kB expression (p < 0.05). The combination treatment was superior in the restoration of normal femoral histoarchitecture and both cortical and trabecular BMD (p < 0.05). Overall, the combined therapy of OVX/E2+ZnHA was more effective than the individual treatments in attenuating excessive bone turnover and preventing osteoporosis.

Abstract Background Broilers are continuously stressed because of the rapid growth rate and the environmental issues associated with industrialized poultry production systems, which lead to higher susceptibility for infection with pathogens. It is well known that vitamin E (Vit. E) and selenium (Se) supplementation have protective functions in such stressful conditions. This protocol was to investigate the impact of Vit. E and/or Se on the production performance, some serum biochemistry, and expression of some growth-related gene in the liver tissue of the broilers. The day-old chicks were allotted into four groups according to the supplement; Control group and groups supplemented with Vit. E and/or Se into Vit. E group (100 mg Vit. E/kg diet), Se group (0.3 mg sodium selenite/kg diet), and Vit E + Se group that supplemented with both Vit. E and Se. Results The data of the present experiment showed that dietary inclusion of Vit. E and/or Se significantly (P ≤ 0.05) improved the production parameters without any side effect on the general health status of the broilers, which indicated by normal serum biochemical parameters. Moreover, the treatments positively affected the expression of some genes related to growth performance including growth hormone receptor (GHR) and insulin-like growth factor 1 (IGF1) in the liver tissue of broilers. Conclusion Dietary supplementation of Vit. E and/or Se improved the production parameters and upregulate the growth-related genes without effect on the general health status of the broilers.

Fenpropathrin (FNP) is one of the commonly used insecticides in agriculture and domestically, leading to environmental and health problems. The goal of the current investigation was to determine how well pomegranate peel extract (PGPE) could prevent the testicular toxicity and oxidative stress induced by FNP. Four groups of male Wistar rats were randomly assigned: negative control (corn oil), PGPE (500 mg/kg BW), positive control (FNP; 15 mg/kg BW, 1/15 LD50), and PGPE + FNP. For four weeks, the rats received their doses daily and orally via gavage. The major phytochemical components (total phenolic, flavonoids, and tannins contents) detected in PGPE by GC-MS included ellagic acid, hydroxymethylfurfurole, guanosine, and pyrogallol with high total phenolic, flavonoids, and tannin contents. FNP-treated rats showed a marked elevation in testicular levels of thiobarbituric acid-reactive substances, hydrogen peroxide, and protein carbonyl content, as well as the activity of aminotransferases and phosphatases. Meanwhile. a significant decline in body weight, gonadosomatic index, glutathione, protein contents, enzymatic antioxidants, and hydroxysteroid dehydrogenase (3β HSD, and 17β HSD) activity was observed. In addition, significant alterations in testicular P53, Cas-3, Bcl-2, IL-β, IL-10, testosterone, follicle-stimulating and luteinizing hormones, and sperm quality were detected. Furthermore, biochemical and molecular changes were corroborated testicular histological abnormalities. Moreover, PGPE-pretreated FNP-intoxicated rats demonstrated considerable improvement in the majority of the studied parameters, when compared to FNP-treated groups. Conclusively, PGPE provided a potent protective effect against the testicular toxicity caused by FNP, due to its antioxidant-active components.

In the original publication [...]