A simulation-based approach to target Zika virus RNA-dependent RNA polymerase with marine compounds for antiviral development.

Despite significant efforts, currently, there is no particular drug available to treat Zika virus (ZIKV) infection, highlighting the urgent need for effective therapeutic interventions. To identify putative inhibitors of the ZIKV RdRp protein's RNA binding function, the present study applied an extensive in-silico drug discovery methodology. The initial phase involved virtual screening using Lipinski's rule of five as a filter, ensuring the selection of molecules with favorable pharmacokinetic properties. This process yielded 238 compounds with promising docking scores, ranging from -6.0 to -7.48 kcal/mol, indicative of their potential binding affinity to the ZIKV RdRp. To refine the selection, these compounds underwent a re-docking process, comparing their binding energies with a reference molecule known for its inhibitory action against RdRp. Remarkably, five compounds, labeled CMNPD30598, CMNPD27464, CMNPD25971, CMNPD27444, and CMNPD16599, demonstrated superior re-docking energies compared to the reference, suggesting a stronger interaction with the RdRp allosteric site. Subsequent molecular dynamics (MD) simulations provided insights into the stability of these complexes over time, reinforcing their potential as RdRp inhibitors. Additionally, the calculation of free binding energies and principal component analysis (PCA) of the free energy landscape offered a deeper understanding of the binding dynamics and energetics. This study not only highlights the utility of marine fungi compounds in antiviral drug discovery but also showcases the power of computational tools in identifying novel therapeutics. The identified compounds represent promising candidates for further experimental validation and development as ZIKV RdRp inhibitors.Communicated by Ramaswamy H. Sarma.

Exploration of human pancreatic alpha-amylase inhibitors from Physalis peruviana for the treatment of type 2 diabetes.

Type 2 Diabetes (T2D), a chronic metabolic disorder characterized by persistent hyperglycemia, accounts for ∼90% of all types of diabetes. Pancreatic α-amylase is a potential drug target for preventing postprandial hyperglycemia and inhibiting T2D in humans. Although many synthetic drugs have been identified against pancreatic α-amylase, however, reported several side effects, and plant-derived natural products are less explored against T2D. This study tested 34 flavonoids derived from the plant Physalis peruviana against the human pancreatic α-amylase (HPA) using in silico computational approaches such as molecular docking and molecular dynamics simulation approaches. Schrödinger, a drug discovery package with modules applicable for molecular docking, protein-ligand interaction analysis, molecular dynamics, post-dynamics simulation, and binding free energy calculation, was employed for all computational studies. Four flavonoids, namely, Chlorogenic acid, Withaperuvin F, Withaperuvin H, and Rutin, were picked based on their docking score ranging between -7.03 kcal/mol and -11.35 kcal/mol compared to the docking score -7.3 kcal/mol of reference ligand, i.e. Myricetin. The molecular dynamics analysis suggested that all flavonoids showed considerable stability within the protein's catalytic pocket, except chlorogenic acid, which showed high deviation during the last 15 ns. However, the interactions observed in initial docking and extracted from the simulation trajectory involved > 90% identical residues, indicating the affinity and stability of the docked flavonoids with the protein. Therefore, all four compounds identified in this study are proposed as promising antidiabetic candidates and should be further considered for their in vitro and in vivo validation.Communicated by Ramaswamy H. Sarma.

Does dietary linseed or canola oil affect lipid metabolism, immunity, and n-3 polyunsaturated fatty acids content in quail eggs?

One of the most intriguing areas of research and innovation in the animal production and food sector recently has been designed-enriched products. These items are regarded as functional foods because they feature components that have advantageous physiological impacts on human health. In the production of poultry, designed eggs constitute a significant category of functional foods. The present study hypothesized that adding different kinds of oils to quail diets will help produce designer eggs rich in omega-3 and 6 fatty acids in addition to enhancing productive performance. So, this study examined how linseed (flaxseed) and canola oils with various levels can affect lipid metabolism, immune function, and the amount of n-3 polyunsaturated fatty acids (n-3 PUFA) in Japanese quail eggs. This work was conducted using 3 different vegetable oils (sunflower, linseed, and canola oils) and 3 different antioxidant supplements (0, 250 mg vitamin E/kg feed, and 1,000 mg ginger/kg feed) in a 3 × 3 factorial experiment. When linseed or canola oil was added to the diet, the number of fatty acids in the egg yolks of Japanese quail layers fell by (12.7 and 18.9%) and (41.4 and 24.6%), respectively. The amounts of saturated and monounsaturated fatty acids in total eggs fell by 21.9 and 14.6% and 24.5 and 15.8%, respectively, at 20 wk of age. However, when linseed and canola oil were added to the diet, the sum n-3 PUFA content in the egg yolk of Japanese quail-laying hens was noticeably raised at 15 and 20 wk of age. At 15 and 20 wk of age, the same groups' total n-6 PUFA content considerably increased compared to the group that did not receive flaxseed. In conclusion, during the laying period of Japanese quail, linseed oil, canola oil, vitamin E, or ginger positively affected productivity, blood hematology, constituents, resistance, lipid digestion system, and antioxidative properties in serum and egg yolk.

Pathological and genetic characterization of foot and mouth disease viruses collected from cattle and water buffalo in Egypt.

Foot-and-mouth disease (FMD), a highly contagious viral disease caused by FMD virus (FMDV) that threatens Egypt's livestock industry. FMDV causes severe economic losses in the livestock, with restriction of international trade from endemic regions. Surveillance for FMDV serotypes circulating in Egypt is urgently needed to assess the epidemiological situation in the country. FMD outbreaks reported in Egypt in between December 2016 and January-March 2017. A cross-sectional study was conducted to identify the FMDV serotypes responsible for the outbreaks and to collect information on the virus's morphopathological effects. Postmortem tissue and clinical samples (oral swabs, vesicular fluids from ruptured vesicles, and blood) were collected from recently deceased and infected animals. Pathological examination revealed classical FMD lesions as vesicular and erosive lesions on epithelial tissues with non-suppurative lymphoplasmacytic myocarditis. Phylogenetic and sequencing analyses demonstrated that FMDV serotype O, EA-3 topotype, VP1 is the prevalent serotype responsible for the pathological alterations and the high mortality in young calves, adult cattle, and water buffalo. The outcomes indicate continuous mutations in the circulating FMDV, which result in the occasional failure of vaccination. Based on these findings, extensive continuous monitoring and serotyping of the existing circulating FMDV isolates and regular vaccination with reevaluation of the currently used vaccine in Egypt are recommended to prevent the recurrence of such outbreaks.

The Influence of a Nanoemulsion of Cardamom Essential Oil on the Growth Performance, Feed Utilization, Carcass Characteristics, and Health Status of Growing Rabbits under a High Ambient Temperature.

Recently, nanotechnology approaches have been employed to enhance the solubility, availability, and efficacy of phytochemicals, overcoming some industrial obstacles and natural biological barriers. In this regard, 120 clinically healthy growing V-line rabbits (5 weeks old) reared during the summer season were divided randomly into four equal experimental groups (30 rabbits each). The first group received a basal diet without the supplementation of the nanoemulsion of cardamom essential oil (NCEO) (0 g/kg diet) and served as a control (NCEO 0). The other groups were given diets containing NCEO at levels of 150 (NCEO 150), 300 (NCEO 300), and 600 (NCEO 600) mg/kg diet, respectively. The growth performance (higher LBW and ADG), feed utilization (lower FCR), dressing percentage, and relative weight of the liver were improved significantly in the NCEO-treated groups compared to the control group. Moreover, the dietary treatment significantly decreased the rectum temperature and respiration rate, minimizing the 350 and 325 mg NECO/kg diets. The erythrocyte count, hematocrit, and hemoglobin concentration were significantly increased (p < 0.05), while white blood cells were significantly diminished (p = 0.0200) in the NCEO300 and NCEO600 groups compared to the control group. Treatment with 300 or 600 mg NCEO/kg significantly increased the blood serum total protein and albumin compared to the control group. Meanwhile, the liver enzymes (AST and ALT), uric acid, and creatinine concentrations decreased significantly in the NCEO300 group compared to the control group. The concentrations of triglycerides and total cholesterol were reduced significantly by the dietary treatment. The total antioxidant capacity, dismutase activity, and glutathione concentration were significantly higher, while the malondialdehyde and protein carbonyl levels were significantly lower in the NCEO300 group than in the control. The inflammatory responses and immunity statuses were improved in the blood serum of the NCEO-treated rabbits compared to the control. Heat-stress-induced pathological perturbations in renal/hepatic tissues and NCEO co-treatment successfully re-established and recovered near-control renal-hepatic morphology. In conclusion, a dietary supplementation of NCEO (300 mg/kg) could effectively enhance growing rabbits' growth indices, feed efficiency, redox balance, immunity, and inflammatory responses during the summer.

Influence of dietary mannan-oligosaccharides supplementation on hematological characteristics, blood biochemical parameters, immune response and histological state of laying hens.

This study aimed to determine the influence of dietary mannan-oligosaccharides (MOS) on the immune system, hematological traits, blood biochemical parameters, and histological state of laying hens. At 34 wk of age, The Mandarah chicken strain's 120 laying hens and 12 cocks were divided into 4 groups, each with 30 hens and 3 cocks. The first group performed as a control group, which nourished on a basal diet. The second, third, and fourth experimental groups received 0.1, 0.2, and 0.5 g/kg of MOS and a base diet, respectively. Birds obtained MOS at numerous doses significantly (P ˂ 0.05) raised serum levels of immunoglobulin Y (IgY), immunoglobulin M (IgM), and avian influenza (AI) antibodies compared to control birds. Furthermore, adding MOS at a level of 0.1 g/kg diet significantly improved the immune response of the control group. Additionally, compared to the control group, treated birds with MOS at various dosages did not significantly enhance hematological parameters such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin, and hematocrit. Compared to control birds, birds fed MOS at all levels exhibited considerably lower serum cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values. Also, compared to other treated birds, MOS-treated birds displayed improved histological examination of the small intestine, isthmus, and testis compared to the control group, particularly in birds fed MOS at 0.1 and 0.2 g/kg diet. It could be concluded that using MOS at 0.1 or 2 g/kg diet can successfully improve the physiological performance and overall health of laying hens.

Influences of dietary supplementation of ginger powder and frankincense oil on productive performance, blood biochemical parameters, oxidative status and tissues histomorphology of laying Japanese quail.

The objective of the current study was to ascertain the effect of using ginger powder or frankincense oil at different levels on the production rate, biochemical properties of blood, and immune response of laying Japanese quail housed from 12 to 21 wk of age. Three hundred sexually mature quail (200 females and 100 males) were distributed among 5 groups at 12 wk of age in a completely randomized design. Group 1: received basal diet not including additives and acted as a control group. Groups 2 and 3: received a basal diet with 250 and 500 mg ginger/kg feed, respectively. Groups 4 and 5: received a basal diet with 200 and 400 mg frankincense oil/kg feed, respectively. Results revealed that egg production parameters of laying Japanese quail were not influenced by ginger or frankincense oil added in all groups tested during experimental periods except at the time (15-18 wks.). Moreover, egg weight was significantly increased only during the period (15-18 wks.) and total period (12-21 wk of age), and group 5 recorded the highest weight during the 2 periods studied. Feed additives did not impact feed consumption or feed conversion ratio (FCR). Except for WBCs, Hb, and monocytes, treatments impacted blood hematological parameters. Also, blood serum parameters were influenced by feed additives, except total protein, albumin, globulin, and creatinine were not influenced. Moreover, histological examination of the spleen was influenced by feed additives. It is concluded that utilizing frankincense oil or ginger powder in diets of laying Japanese quails enhanced blood serum properties and improved reproductive and productive performance.

The efficacy of polyphenols as an antioxidant agent: An updated review.

Global production of the two major poultry products, meat and eggs, has increased quickly. This, in turn, indicates both the relatively low cost and the customers' desire for these secure and high-quality products. Natural feed additives have become increasingly popular to preserve and enhance the health and productivity of poultry and livestock. We consume a lot of polyphenols, which are a kind of micronutrient. These are phytochemicals with positive effects on cardiovascular, cognitive, anti-inflammatory, detoxifying, anti-tumor, anti-pathogen, a catalyst for growth, and immunomodulating functions, among extra health advantages. Furthermore, high quantities of polyphenols have unknown and occasionally unfavorable impacts on the digestive tract health, nutrient assimilation, the activity of digestive enzymes, vitamin and mineral assimilation, the performance of the laying hens, and the quality of the eggs. This review clarifies the numerous sources, categories, biological functions, potential limitations on usage, and effects of polyphenols on poultry performance, egg composition, exterior and interior quality traits.

Combination of furosemide, gold, and dopamine as a potential therapy for breast cancer.

Breast cancer is one of the leading causes of death in women worldwide. Initially, it develops in the epithelium of the ducts or lobules of the breast glandular tissues with limited growth and the potential to metastasize. It is a highly heterogeneous malignancy; however, the common molecular mechanisms could help identify new targeted drugs for treating its subtypes. This study uses computational drug repositioning approaches to explore fresh drug candidates for breast cancer treatment. We also implemented reversal gene expression and gene expression-based signatures to explore novel drug candidates computationally. The drug activity profiles and related gene expression changes were acquired from the DrugBank, PubChem, and LINCS databases, and then in silico drug screening, molecular dynamics (MD) simulation, replica exchange MD simulations, and simulated annealing molecular dynamics (SAMD) simulations were conducted to discover and verify the valid drug candidates. We have found that compounds like furosemide, gold, and dopamine showed significant outcomes. Furthermore, the expression of genes related to breast cancer was observed to be reversed by these shortlisted drugs. Therefore, we postulate that combining furosemide, gold, and dopamine would be a potential combination therapy measurement for breast cancer patients.

Utilization of Deep Convolutional Neural Networks for Accurate Chest X-Ray Diagnosis and Disease Detection.

Chest radiography is a widely used diagnostic imaging procedure in medical practice, which involves prompt reporting of future imaging tests and diagnosis of diseases in the images. In this study, a critical phase in the radiology workflow is automated using the three convolutional neural network (CNN) models, viz. DenseNet121, ResNet50, and EfficientNetB1 for fast and accurate detection of 14 class labels of thoracic pathology diseases based on chest radiography. These models were evaluated on an AUC score for normal versus abnormal chest radiographs using 112120 chest X-ray14 datasets containing various class labels of thoracic pathology diseases to predict the probability of individual diseases and warn clinicians of potential suspicious findings. With DenseNet121, the AUROC scores for hernia and emphysema were predicted as 0.9450 and 0.9120, respectively. Compared to the score values obtained for each class on the dataset, the DenseNet121 outperformed the other two models. This article also aims to develop an automated server to capture fourteen thoracic pathology disease results using a tensor processing unit (TPU). The results of this study demonstrate that our dataset can be used to train models with high diagnostic accuracy for predicting the likelihood of 14 different diseases in abnormal chest radiographs, enabling accurate and efficient discrimination between different types of chest radiographs. This has the potential to bring benefits to various stakeholders and improve patient care.

Enhanced Production of Active Photosynthetic and Biochemical Molecules in Silybum marianum L. Using Biotic and Abiotic Elicitors in Hydroponic Culture.

Elicitors are stressors that activate secondary pathways that lead to the increased production of bioactive molecules in plants. Different elicitors including the fungus Aspergillus niger (0.2 g/L), methyl jasmonate (MeJA, 100 µM/L), and silver nanoparticles (1 µg/L) were added, individually and in combination, in a hydroponic medium. The application of these elicitors in hydroponic culture significantly increased the concentration of photosynthetic pigments and total phenolic contents. The treatment with MeJA (methyl jasmonate) (100 µM/L) and the co-treatment of MeJA and AgNPs (silver nanoparticles) (100 µM/L + 1 µg/L) exhibited the highest chlorophyll a (29 µg g-1 FW) and chlorophyll b (33.6 µg g-1 FW) contents, respectively. The elicitor MeJA (100 µM/L) gave a substantial rise in chlorophyll a and b and total chlorophyll contents. Likewise, a significant rise in carotenoid contents (9 µg/g FW) was also observed when subjected to meJA (100 µM/L). For the phenolic content, the treatment with meJA (100 µM/L) proved to be very effective. Nevertheless, the highest production (431 µg/g FW) was observed when treated with AgNPs (1 µg/L). The treatments with various elicitors in this study had a significant effect on flavonoid and lignin content. The highest concentration of flavonoids and lignin was observed when MeJA (100 mM) was used as an elicitor, following a 72-h treatment period. Hence, for different plant metabolites, the treatment with meJA (100 µM/L) and a co-treatment of MeJA and AgNPs (100 µM/L + 1 µg/L) under prolonged exposure times of 120-144 h proved to be the most promising in the accretion of valuable bioactive molecules. The study opens new insights into the use of these elicitors, individually or in combination, by using different concentrations and compositions.

Effect of Nitrogen in Combination with Different Levels of Sulfur on Wheat Growth and Yield.

As macronutrients, management of nitrogen (N) and sulfur (S) is prime in importance when wheat is cultivated. Both have a significant impact on the improvement of growth and yield attributes. In addition, S and N also play an imperative role in the enhancement of seed protein contents. However, the need of the time is the selection of their optimum application rate for the achievement of maximum wheat productivity. That is why the current study was planned to examine the impact of variable application rates of S and N on wheat. There are 12 treatments, i.e., control (no nitrogen (0N) + no sulfur (0S)), 40 kg/ha N (40N + 0S), 80 kg/ha N (80N + 0S), 120 kg/ha N (120N + 0S), 30 kg/ha sulfur (30S), 40N + 30S, 80N + 30S, 120N + 30S, 60 kg/ha sulfur (60S), 40N + 60S, 80N + 60S, and 120N + 60S, applied in three replications. The results showed that plant height, grains/spike, spike/m2, and 1000 grain weight were significantly improved by the addition of 120N + 60S. A significant enhancement of grain N contents, N uptake, and protein contents of wheat validated the efficient role of 120N + 60S over 0N and 0S. In conclusion, 120N + 60S is a better treatment for the achievement of maximum wheat yield. More investigations under variable soil textures and climatic conditions are suggested under different climates to declare 120N + 60S as the best amendment for wheat growth and yield improvement.

Therapeutic Antiaging Strategies.

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects.

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases.

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

Flavonoids as Promising Neuroprotectants and Their Therapeutic Potential against Alzheimer's Disease.

Alzheimer's disease (AD) is one of the serious and progressive neurodegenerative disorders in the elderly worldwide. Various genetic, environmental, and lifestyle factors are associated with its pathogenesis that affect neuronal cells to degenerate over the period of time. AD is characterized by cognitive dysfunctions, behavioural disability, and psychological impairments due to the accumulation of amyloid beta (Aß) peptides and neurofibrillary tangles (NFT). Several research reports have shown that flavonoids are the polyphenolic compounds that significantly improve cognitive functions and inhibit or delay the amyloid beta aggregation or NFT formation in AD. Current research has uncovered that dietary use of flavonoid-rich food sources essentially increases intellectual abilities and postpones or hinders the senescence cycle and related neurodegenerative problems including AD. During AD pathogenesis, multiple signalling pathways are involved and to target a single pathway may relieve the symptoms but not provides the permanent cure. Flavonoids communicate with different signalling pathways and adjust their activities, accordingly prompting valuable neuroprotective impacts. Flavonoids likewise hamper the movement of obsessive indications of neurodegenerative disorders by hindering neuronal apoptosis incited by neurotoxic substances. In this short review, we briefly discussed about the classification of flavonoids and their neuroprotective properties that could be used as a potential source for the treatment of AD. In this review, we also highlight the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production.

Photocatalytic Activity Induced by Metal Nanoparticles Synthesized by Sustainable Approaches: A Comprehensive Review.

Nanotechnology is a fast-expanding area with a wide range of applications in science, engineering, health, pharmacy, and other fields. Among many techniques that are employed toward the production of nanoparticles, synthesis using green technologies is the simplest and environment friendly. Nanoparticles produced from plant extracts have become a very popular subject of study in recent decades due to their diverse advantages such as low-cost synthesis, product stability, and ecofriendly protocols. These merits have prompted the development of nanoparticles from a variety of sources, including bacteria, fungi, algae, proteins, enzymes, etc., allowing for large-scale production with minimal contamination. However, nanoparticles obtained from plant extracts and phytochemicals exhibit greater reduction and stabilization and hence have proven the diversity of properties, like catalyst/photocatalyst, magnetic, antibacterial, cytotoxicity, circulating tumor deoxy ribo nucleic acid (CT-DNA) binding, gas sensing, etc. In the current scenario, nanoparticles can also play a critical role in cleaning wastewater and making it viable for a variety of operations. Nano-sized photocatalysts have a great scope toward the removal of large pollutants like organic dyes, heavy metals, and pesticides in an eco-friendly and sustainable manner from industrial effluents. Thus, in this review article, we discuss the synthesis of several metal nanoparticles using diverse plant extracts, as well as their characterization via techniques like UV-vis (ultraviolet-visible), XRD (X-ray diffraction), SEM (scanning electron microscopy), TEM (transmission electron microscopy), FTIR (Fourier transform infrared spectroscopy), etc., and catalytic activity on various hazardous systems.

Identification of Novel and Safe Fungicidal Molecules against Fusarium oxysporum from Plant Essential Oils: In Vitro and Computational Approaches.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum, Trachyspermum ammi, Azadirachta indica, Syzygium aromaticum, Moringa oleifera, Mentha spicata, Eucalyptus grandis, Allium sativum, and Citrus sinensis were tested against Fusarium oxysporum. Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50 µl/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100 µl/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m2) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO. Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum.

In Silico and In Vitro Screening Constituents of Eclipta alba Leaf Extract to Reveal Antimicrobial Potential.

Phytochemicals have been shown to possess multiple bioactives and have been reported to showcase many medicinal effects. A similar kind of evaluation of phytoconstituents for their antimicrobial action has been reported, based on in vitro and in silico data. The goal of the research was to explore bioactive phytoconstituents of Eclipta alba leaf for antimicrobial activity. The antimicrobial activity was validated by both molecular docking and antimicrobial assay. Bioactive metabolites were identified using GC-MS. The antimicrobial and antimycobacterial activity of Eclipta alba leaves was investigated using the Kirby-Bauer well diffusion method and the rapid culture-MGIT™ DST method against a variety of human pathogens, as well as Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin. Eclipta alba's GC-MS studies confirmed the detection of 17 bioactive constituents. The extract demonstrates the highest antibacterial activity against Escherichia coli (sensitive), Pseudomonas aeruginosa (sensitive) and methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa susceptible and MRSA (sensitive) with zone of inhibition of 27 mm, 24 mm, and 32 mm respectively. The extract showed no effect on Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin in antimycobacterial activity testing. Molecular docking investigation revealed that three compounds (phthalic acid, isobutyl octadecyl ester, hexadecanoic acid, 1(hydroxymethyl)1,2-ethanediylester, and 2,myristynoyl pantetheine) have generated the best results in terms of binding energies and significant interactions with key residues of target protein 3-hydroxydecanoyl-acyl carrier protein dehydratase (FabA) and confirm its activity as antimicrobial inhibitors. These two-dimensional plots show significant protein-ligand binding interactions (van der Waals interactions, hydrogen bond, alkyl, and Pi-alkyl interactions). ADMET (absorption, distribution, metabolism, excretion, and toxicity) results additionally support the drug-likeness characteristics of concluded potential compounds. The experimental and computational results demonstrated that methanolic extract of Eclipta alba leaves had antimicrobial effects for specific infections due to the presence of phytochemical compounds.

Identification of Effective and Nonpromiscuous Antidiabetic Drug Molecules from Penicillium Species.

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of ß-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for ß-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å2. log P < 5 was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between -9.2 and -4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.

Incidence of adhesions in patients using liraglutide before laparoscopic sleeve gastrectomy.

BACKGROUND: The current study objectively identified the incidence of adhesions between the stomach and pancreas in laparoscopic sleeve gastrectomy (LSG) patients on liraglutide (cases group) and off (control group) liraglutide. METHODS: This observational prospective study was conducted in the Department of General Surgery at Saudi German Hospital, Al-Aseer, Saudi Arabia (SGH) after approval by the Institutional Review Board. 117 patients with prior use of liraglutide and 101 patients with no liraglutide use scheduled for LSG over 12 months were included. Inclusion criteria included patients undergoing LSG with or without prior use of liraglutide. Exclusion criteria included patients with prior abdominal surgeries, bariatric surgery revisions, prior upper GI scope showing gastritis, Gastroesophageal Reflux Disease (GERD) or any other pathology, and other known causes of other causes of pancreatitis. Using laparoscopy obtained imaging during LSG cases adhesions between the posterior stomach and pancreas were identified. RESULTS: The mean age of the patients in the cases and control groups was 32.44 ± 9.90 years and 28.23 ± 8.48 years (p = 0.001). The mean BMI of patients in the cases and control groups was 43.56 ± 4.59 and 45.00 ± 4.78, respectively (p = 0.024). 85% of the patients were females, while 17.0% were males in the cases group. 53.5% of the patients were females, while 47.0% were males in the control group (p < 0.001). In the cases group, 48.7% of patients had stopped liraglutide for no obvious reason. Under the cases group, 77.8% of the patients had no adhesions, while 22.2% had adhesions. Under the controls group, no adhesions were seen (p < 0.001). CONCLUSIONS: Our results for the first time demonstrate an incidence of adhesions in 22.2% of patients undergoing LSG on prior liraglutide intake (p < 0.001). This study brings to light the possibility of adhesions in patients with prior exposure to liraglutide undergoing LSG. Surgeons performing LSG in patients with prior exposure to liraglutide should be cognizant of this possibility, thereby requiring careful meticulous dissection.