Green Synthesis of Silver Nanoparticles from Allium cepa L. Peel Extract, Their Antioxidant, Antipathogenic, and Anticholinesterase Activity.

The present work deals with the green synthesis and characterization of silver nanoparticles (AgNPs) using Allium cepa (yellowish peel) and the evaluation of its antimicrobial, antioxidant, and anticholinesterase activities. For the synthesis of AgNPs, peel aqueous extract (200 mL) was treated with a 40 mM AgNO3 solution (200 mL) at room temperature, and a color change was observed. In UV-Visible spectroscopy, an absorption peak formation at ~439 nm was the sign that AgNPs were present in the reaction solution. UV-vis, FE-SEM, TEM, EDX, AFM, XRD, TG/DT analyses, and Zetasizer techniques were used to characterize the biosynthesized nanoparticles. The crystal average size and zeta potential of AC-AgNPs with predominantly spherical shapes were measured as 19.47 ± 1.12 nm and -13.1 mV, respectively. Pathogenic microorganisms Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were used for the Minimum Inhibition Concentration (MIC) test. When compared to tested standard antibiotics, AC-AgNPs demonstrated good growth inhibitory activities on P. aeuruginosa, B. subtilis, and S. aureus strains. In vitro, the antioxidant properties of AC-AgNPs were measured using different spectrophotometric techniques. In the ß-Carotene linoleic acid lipid peroxidation assay, AC-AgNPs showed the strongest antioxidant activity with an IC50 value of 116.9 µg/mL, followed by metal-chelating capacity and ABTS cation radical scavenging activity with IC50 values of 120.4 µg/mL and 128.5 µg/mL, respectively. The inhibitory effects of produced AgNPs on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were determined using spectrophotometric techniques. This study provides an eco-friendly, inexpensive, and easy method for the synthesis of AgNPs that can be used for biomedical activities and also has other possible industrial applications.

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay.

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.

Improvement of lipid profile and hepatic oxidative stress in high-fat-diet induced hyperlipidemic Swiss albino rats by Piper betle juice: evidences from in vivo and in silico studies.

Piper betle L. leaves are very popular and traditionally used to chew with betel nut in many Asian countries. In this study, P. betle leaves juice (PBJ) was subjected to evaluation for its antihyperlipidemic activity in the high-fat-diet-induced hyperlipidemic rats model. Swiss albino rats were allowed to high-fat- diet for one month, followed by concurrent administration of PBJ for another month. The rats were then sacrificed and collected blood, tissues and organs. Pharmacokinetic, toxicological studies and molecular docking studies were performed using SwissADME, admetSAR and schrodinger suit-2017. Our investigation showed a promising effect of PBJ on body weight, lipid profile, oxidative and antioxidative enzymes, and the principle enzyme responsible for the synthesis of cholesterol. PBJ at 0.5 - 3.0 mL/rat significantly reduced body weight of hyperlipidemic rats compared to control. PBJ at the doses of 1.0, 1.5, 2.0, and 3.0 mL/rat significantly (p<0.05, p<0.01, p<0.001) improved the levels of TC, LDL-c, TG, HDL-c and VLDL-c. Similarly, PBJ doses starting from 1.0 mL/rat to 3.0 mL/rat reduced the oxidative biomarkers AST, ALT, ALP, and creatinine. The level of HMG-CoA was significantly reduced by PBJ doses 1.5, 2, and 3 ml/rat. A number of compounds have been found to have good pharmacokinetic profile and safety and 4-coumaroylquinic acid exerted the best docking score among them. Thus our findings clearly demonstrated the potential lipid-lowering activities of PBJ both in vivo and in silico studies. PBJ can be a good candidate for the development of antihyperlipidemic medication or as an alternative medicine.

Chemico-Pharmacological Screening of the Methanol Extract of Gynura nepalensis D.C. Deciphered Promising Antioxidant and Hepatoprotective Potentials: Evidenced from in vitro, in vivo, and Computer-Aided Studies.

Gynura nepalensis D.C. (family: Asteraceae) has abundant uses in the alternative medicinal practice, and this species is commonly used in the treatment of diabetes, rheumatism, cuts or wounds, asthma, kidney stones, cough, urinary tract bleeding, gall bladder stones, hepatitis, diarrhea, hemorrhoids, constipation, vomiting, fertility problems, blood poisoning, septicemia, skin allergy, indigestion, high cholesterol levels, and so on. This study aims to investigate the hepatoprotective and antioxidant potential of the methanol extract of the Gynura nepalensis D.C. (GNME) along with chemical profiling with phytochemical screening. Moreover, prospective phytocompounds have been screened virtually to present the binding affinity of the bioactive components to the hepatic and oxidative receptors. In the hepatoprotective study, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), and lipid peroxidation (LP) and total bilirubin (TB) have been assessed, and in the antioxidant study, the DPPH free radical scavenging, total antioxidant flavonoid, and phenolic contents were determined. Moreover, the molecular binding affinity of the bioactive component of the plant has been analyzed using PyRx AutoDock Vina, Chimera, and Discovery Studio software. The plant extract showed dose-dependent hepatoprotective potential (p < 0.05, 0.01, 0.001) as well as strong antioxidant properties. Moreover, hepatoprotective and antioxidant molecular docking studies revealed a result varying from −2.90 kcal/mol to −10.1 kcal/mol. 4,5-dicaffeoylquinic acid and chlorogenic acid revealed the highest binding affinity among the selected molecules. However, the plant showed portent antioxidant and hepatoprotective properties in the in vitro, in vivo, and in silico models, and it is presumed that the hepatoprotective properties of the plant extract have occurred due to the presence of the vast bioactive chemical compounds as well as their antioxidant properties. Therefore, advanced studies are recommended to elucidate the pharmacological properties of the plant extracts.

Ethnobotanical Uses, Phytochemistry, Toxicology, and Pharmacological Properties of Euphorbia neriifolia Linn. against Infectious Diseases: A Comprehensive Review.

Medicinal plants have considerable potential as antimicrobial agents due to the presence of secondary metabolites. This comprehensive overview aims to summarize the classification, morphology, and ethnobotanical uses of Euphorbia neriifolia L. and its derived phytochemicals with the recent updates on the pharmacological properties against emerging infectious diseases, mainly focusing on bacterial, viral, fungal, and parasitic infections. The data were collected from electronic databases, including Google Scholar, PubMed, Semantic Scholar, ScienceDirect, and SpringerLink by utilizing several keywords like 'Euphorbia neriifolia', 'phytoconstituents', 'traditional uses', 'ethnopharmacological uses', 'infectious diseases', 'molecular mechanisms', 'COVID-19', 'bacterial infection', 'viral infection', etc. The results related to the antimicrobial actions of these plant extracts and their derived phytochemicals were carefully reviewed and summarized. Euphol, monohydroxy triterpene, nerifoliol, taraxerol, ß-amyrin, glut-5-(10)-en-1-one, neriifolione, and cycloartenol are the leading secondary metabolites reported in phytochemical investigations. These chemicals have been shown to possess a wide spectrum of biological functions. Different extracts of E. neriifolia exerted antimicrobial activities against various pathogens to different extents. Moreover, major phytoconstituents present in this plant, such as quercetin, rutin, friedelin, taraxerol, epitaraxerol, taraxeryl acetate, 3ß-friedelanol, 3ß-acetoxy friedelane, 3ß-simiarenol, afzelin, 24-methylene cycloarenol, ingenol triacetate, and ß-amyrin, showed significant antimicrobial activities against various pathogens that are responsible for emerging infectious diseases. This plant and the phytoconstituents, such as flavonoids, monoterpenoids, diterpenoids, triterpenoids, and alkaloids, have been found to have significant antimicrobial properties. The current evidence suggests that they might be used as leads in the development of more effective drugs to treat emerging infectious diseases, including the 2019 coronavirus disease (COVID-19).

Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors.

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a-5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.

An Evaluation of Antimicrobial, Anticancer, Anti-Inflammatory and Antioxidant Activities of Silver Nanoparticles Synthesized from Leaf Extract of Madhuca longifolia Utilizing Quantitative and Qualitative Methods.

In the current decade, nanoparticles are synthesized using solvents that are environmentally friendly. A number of nanoparticles have been synthesized at room temperature using water as a solvent, such as gold (Au) and silver (Ag) nanoparticles. As part of nanotechnology, nanoparticles are synthesized through biological processes. Biological methods are the preferred method for the synthesis of inorganic nanoparticles (AgNPs) as a result of their simple and non-hazardous nature. Nanoparticles of silver are used in a variety of applications, including catalysts, spectrally selective coatings for solar absorption, optical objectives, pharmaceutical constituents, and chemical and biological sensing. Antimicrobial agents are among the top uses of silver nanoparticles. In the current study, silver nanoparticles were biologically manufactured through Madhuca longifolia, and their antibacterial activity against pathogenic microorganisms, anticancer, anti-inflammatory, and antioxidant activities were assessed. UV-Vis spectroscopy, XRD (X-ray diffraction), transmission electron microscopy, Zeta Potential, and FTIR were used to characterize silver nanoparticles. The current work describes a cheap and environmentally friendly method to synthesize silver nanoparticles from silver nitrate solution by using plant crude extract as a reducing agent.

Coriandrum sativum L.: A Review on Ethnopharmacology, Phytochemistry, and Cardiovascular Benefits.

Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The cardiovascular benefits of C. sativum have not been summarized before, hence this review aims to further evaluate and discuss its effectiveness in cardiovascular diseases, according to the recent literature. An electronic search for literature was carried out using the following databases: PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews. Articles were gathered from the inception of the database until August 2021. Moreover, the traditional uses and phytochemistry of coriander were surveyed in the original resources and summarized. As a result, most of the studies that cover cardiovascular benefits and fulfilled the eligibility criteria were in vivo, while only a few were in vitro and clinical studies. In conclusion, C. sativum can be deemed a functional food due to its wide range of cardiovascular benefits such as antihypertensive, anti-atherogenic, antiarrhythmic, hypolipidemic as well as cardioprotective effects.

Screening of Baccaurea ramiflora (Lour.) extracts for cytotoxic, analgesic, anti-inflammatory, neuropharmacological and antidiarrheal activities.

BACKGROUND: It has been observed that the various part of Baccaurea ramiflora plant is used in rheumatoid arthritis, cellulitis, abscesses, constipation and injuries. This plant also has anticholinergic, hypolipidemic, hypoglycemic, antiviral, antioxidant, diuretic and cytotoxic activities. The present studyaimed to assess the cytotoxic, analgesic, anti-inflammatory, CNS depressant and antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and seeds in mice model. METHODS: The cytotoxic activity was determined by brine shrimp lethality bioassay; anti-nociceptive activity was determined by acetic acid-induced writhing, formalin- induced licking and biting, and tail immersion methods. The anti-inflammatory, CNS depressant and anti-diarrheal activities were assessed by carrageenan-induced hind paw edema, the open field and hole cross tests, and castor oil-induced diarrheal methods, respectively. The data were analyzed by one way ANOVA (analysis of variance) followed by Dunnett's test. RESULTS: In brine shrimp lethality bioassay, the LC50 values of the methanol extracts of Baccaurea ramiflora pulp and seed were 40 µg/mL and 10 µg/mL, respectively. Our investigation showed that Baccaurea ramiflora pulp and seed extracts (200 mg/kg) inhibited acetic acid induced pain 67.51 and 66.08%, respectively (p < 0.05) that was strongly comparable with that of Ibuprofen (72%) (p < 0.05). The Baccaurea ramiflora pulp and seed extracts (200 mg/kg) significantly (p < 0.05) reduced 58.5 and 53.4 in early and 80.8%, 76.61% in late phase of formalin-induced licking and biting. At 60 and 90 min pulp and seed extracts (200 mg/kg) inhibited nociception of thermal stimulus 50.16 and 62.4%, respectively (p < 0.05) which was comparable with the standard (morphine, 75.9% inhibition). The pulp and seed extracts (200 mg/kg) significantly (p < 0.05) reduced inflammation (42.00 and 55.22%, respectively) in carrageenan-induced hind paw edema and defecations (59.7 and 63.03%, respectively) in castor oil induced diarrhea. Both the extracts showed high sedative activity at 30, 60, 90, and 120 min. CONCLUSION: Our investigation demonstrated significant cytotoxic, analgesic, anti-inflammatory, CNS depressant and antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and seeds (200 mg/kg).

The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles. Several functional foods have therapeutic potential to treat chronic diseases including diabetes. The therapeutic potential of pomegranate has been stated by multitudinous scientists. The present study aimed to evaluate the effects of pomegranate juice and seed powder on the levels of plasma glucose and insulin, inflammatory biomarkers, lipid profiles, and health of the pancreatic islets of Langerhans in streptozotocin (STZ)-nicotinamide (NAD) induced T2DM Sprague Dawley (SD) rats. METHODS: Forty healthy male SD rats were induced to diabetes with a single dose intra-peritoneal administration of STZ (60 mg/kg b.w.) - NAD (120 mg/kg b.w.). Diabetic rats were orally administered with 1 mL of pomegranate fresh juice (PJ) or 100 mg pomegranate seed powder in 1 mL distilled water (PS), or 5 mg/kg b.w. of glibenclamide every day for 21 days. Rats in all groups were sacrificed on day 22. The obtained data was analyzed by SPSS software (v: 22) using One-way analysis of variance (ANOVA). RESULTS: The results showed that PJ and PS treatment had slight but non-significant reduction of plasma glucose concentration, and no impact on plasma insulin compared to diabetic control (DC) group. PJ lowered the plasma total cholesterol (TC) and triglyceride (TG) significantly, and low-density lipoproteins (LDL) non-significantly compared to DC group. In contrast, PS treatment significantly raised plasma TC, LDL, and high-density lipoproteins (HDL) levels compared to the DC rats. Moreover, the administration of PJ and PS significantly reduced the levels of plasma inflammatory biomarkers, which were actively raised in diabetic rats. Only PJ treated group showed significant repairment and restoration signs in islets of Langerhans. Besides, PJ possessed preventative impact against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals almost 2.5 folds more than PS. CONCLUSIONS: Our findings suggest that active constituents with high antioxidant properties present in PJ are responsible for its anti-hyperlipidemic and anti-inflammatory effects, likewise the restoration effect on the damaged islets of Langerhans in experimental rats. Hence, the pharmacological, biochemical, and histopathological profiles of PJ treated rats obviously indicated its helpful effects in amelioration of diabetes-associated complications.

Free radical scavenging, antidiarrheal and anthelmintic activity of Pistia stratiotes L. extracts and its phytochemical analysis.

In this phyto-pharmacological screening of Pistia stratiotes L leaf and root extracts each separately in two different solvents demonstrated its potential medicinal value. Apparent antioxidant value is demonstrated by DPPH, Nitric oxide scavenging and Ferric ion reducing method. Additionally, total flavonoid and phenolic compounds were measured. The leaf methanolic extract scavenged both nitric oxide (NO) and DPPH radical with a dose dependent manner. But the pet ether fraction of root was found to have highest efficacy in Fe(3±) reducing power assay. Flavonoid was found to contain highest in the pet ether fraction of root (411.35mg/g) in terms of quercetin equivalent, similarly highest amount (34.96mg/g) of total phenolic compounds (assayed as gallic acid equivalents) were found to contain in the same fraction. The methanolic fractions appeared less cytotoxic compared to pet ether extracts. The plant extracts caused a dose dependent decrease in faecal droppings in both castor oil and magnesium sulphate induced diarrhea, where as leaf extracts in each solvent appeared most effective. Also, the plant extracts showed anthelmintic activity in earthworm by inducing paralysis and death in a dose dependent manner. At highest doses (50 mg/ml) all fractions were almost effective as the positive control piperazine citrate (10 mg/ml). Thus, besides this cytotoxic effect it's traditional claim for therapeutic use can never be overlooked.

Withanone as an Emerging Anticancer Agent and Understanding Its Molecular Mechanisms: Experimental and Computational Evidence.

Despite decades of research and effort, treating cancer is still a challenging task. Current conventional treatments are still unsatisfactory to fully eliminate and prevent re-emergence or relapses, and targeted or personalised therapy, which are more effective in managing cancer, may be unattainable or inaccessible for some. In the past, research in natural products have yielded some of the most commonly used cancer treatment drugs known today. Hence it is possible more are awaiting to be discovered. Withanone, a common withanolide found in the Ayurvedic herb Withania somnifera, has been claimed to possess multiple benefits capable of treating cancer. This review focuses on the potential of withanone as a safe cancer treatment drug based on the pharmacokinetic profile and molecular mechanisms of actions of withanone. Through these in silico and in vitro studies discussed in this review, withanone showspotent anticancer activities and interactions with molecular targets involved in cancer progression. Furthermore, some evidences also show the selective killing property of withanone, which highlights the safety and specificity of withanone in targeting cancer cell. By compiling these evidences, this review hopes to spark interest for future research to be conducted in more extensive studies involving withanone to generate more data, especially involving in vivo experiments and toxicity evaluation of withanone.

A 3D co-culture intestinal organoid system for exploring glucose metabolism.

Many treatments have been used for glucose metabolism diseases such as type 2 diabetes, and all of those treatments have several advantages as well as limitations. This review introduces a 3D co-culture intestinal organoid system developed from stem cells, which has the special function of simulating human tissues. Recent studies have revealed that the gut is an important site for exploring the interactions among glucose metabolism, gut microbial metabolism, and gut microbiota. Therefore, 3D intestinal organoid systems can be used to imitate the congenital errors of human gut development, drug screening, food transportation and toxicity analysis. The intestinal organoid system construction methods and their progress as compared with traditional 2D culture methods have also been summarised in the manuscript. This paper discusses the research progress in terms of intestinal organoids applicable to glucose metabolism and provides new ideas for developing anti-diabetic drugs with high efficiency and low toxicity.

Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms.

Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.

Modified coptisine derivatives as an inhibitor against pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg virus by molecular docking and molecular dynamics simulation-based drug design approach.

During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses.

Role of pattern recognition receptors in sensing Mycobacterium tuberculosis.

Mycobacterium tuberculosis is one of the major invasive intracellular pathogens causing most deaths by a single infectious agent. The interaction between host immune cells and this pathogen is the focal point of the disease, Tuberculosis. Host immune cells not only mount the protective action against this pathogen but also serve as the primary niche for growth. Thus, recognition of this pathogen by host immune cells and following signaling cascades are key dictators of the disease state. Immune cells, mainly belonging to myeloid cell lineage, recognize a wide variety of Mycobacterium tuberculosis ligands ranging from carbohydrate and lipids to proteins to nucleic acids by different membrane-bound and soluble pattern recognition receptors. Simultaneous interaction between different host receptors and pathogen ligands leads to immune-inflammatory response as well as contributes to virulence. This review summarizes the contribution of pattern recognition receptors of host immune cells in recognizing Mycobacterium tuberculosis and subsequent initiation of signaling pathways to provide the molecular insight of the specific Mtb ligands interacting with specific PRR, key adaptor molecules of the downstream signaling pathways and the resultant effector functions which will aid in identifying novel drug targets, and developing novel drugs and adjuvants.

Assessing the Self-reported After Events Following Immunization of COVID-19 Vaccines in Turkey and Bangladesh.

Though mass vaccination programs helped to reduce the severity of the ongoing pandemic, various unwanted effects were reported in Turkey and Bangladesh after taking vaccines. The purpose of this study was to evaluate and compare the adverse effects of several vaccines in Turkey and Bangladesh and how the population of both countries prioritizes the continuation of vaccination compared to the side effects. An online survey with a pretest was conducted to gather data over the research period from July 10, 2021 to December 10, 2021. Finally, the questionnaire was shared with the mass population of Turkey and Bangladesh who have received at least one or two doses of the COVID-19 vaccines. The quality of the questionnaire was evaluated with Cronbach's alpha test. The study consisted of 1508 respondents from Bangladesh and 602 respondents from Turkey. Among the total 2110 respondents, 50.0% were male 66.8% were from the 18-30 years age range, and 77.5% reported living in the city area. Among all the respondents, 64.99% of those vaccinated in Bangladesh and 67.28% of those vaccinated in Turkey reported side effects after vaccinations. Participants receiving mRNA vaccines (Pfizer and Moderna) experienced the most side effects, with many reporting pain at the injection site in both nations. Following that, fever, body pain, and headache were common in Bangladesh, whereas body pain, fatigue, and arm numbness were common in Turkey. The study found no significant adverse events reported in Turkey and Bangladesh following the first and second doses of COVID-19 vaccination. These COVID-19 vaccines showed similar patterns of efficacy and safety during the short period of analysis. Vaccines from different manufacturers showed a non-significant level of adverse events during this binational AEFI approach to COVID-19 vaccines. More studies are recommended on the efficacy and safety of several vaccines to discover unexpected effects.

Preliminary study of the immunostimulating activity of an ayurvedic preparation, Kanakasava, on the splenic cells of BALB/c mice in vitro.

CONTEXT: Immunostimulant plays an important role to prevent infections when defensive capacity of body is impaired, commonly occur with aging, cancer, diabetes, and sepsis. Kanakasava (KNK) is a polyherbal ayurvedic preparation used since ancient times for the treatment of respiratory diseases and to improve immunity. OBJECTIVE: The present study evaluated the immunostimulating potential of KNK. MATERIALS AND METHODS: The immunostimulating activity of KNK was evaluated by measuring immunoglobulin M (IgM) production and splenocyte proliferation in vitro. BALB/c mice splenocytes were treated with 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, and 4% (v/v) of KNK, and the cells were subcultured at 37°C, humidified atmosphere containing 5% CO(2) for 120 h. The production of IgM in cultured supernatants were determined by an enzyme-linked immunosorbent assay (ELISA) and the proliferations of cells were measured by the 3-(4,5-dimethylthiazol-2-y)-2,5-diphenylterazolium bromide (MTT) method. RESULTS AND DISCUSSION: KNK at the doses of 0.25, 0.5, 0.75, 1, and 1.5% (v/v) significantly augmented polyclonal IgM production (1.211, 1.260, 1.274, 1.180, and 1.028 µg/mL, respectively) compared to control (0.246 µg/mL). Similarly, the same doses stimulated the proliferation of splenocytes as well (Abs. 0.270, 0.281, 0.368, 0.328, and 0.301, respectively, measured at 570 nm) compared to untreated cells (Abs. 0.137). The activity of KNK was not retarded by the treatment of cells with polymixin B. Thus, our results demonstrate that KNK possesses immunostimulating potential that acts through the induction of lymphocytes for proliferation and IgM production. CONCLUSION: KNK may be useful for strengthening immune responses in case of insufficient or impaired immunity.

Nutraceutical potentials of algal ulvan for healthy aging.

Several theories for aging are constantly put forth to explain the underlying mechanisms. Oxidative stress, DNA dysfunction, inflammation, and mitochondrial dysfunction, along with the release of cytochrome c are some of these theories. Diseases such as type 2 diabetes mellitus, intestinal dysfunction, cardiovascular diseases, hepatic injury, and even cancer develop with age and eventually cause death. Ulva polysaccharides, owing to their special structures and various functions, have emerged as desirable materials for keeping healthy. These polysaccharide structures are found to be closely related to the extraction methods, seaweed strains, and culture conditions. Ulvan is a promising bioactive substance, a potential functional food, which can regulate immune cells to augment inflammation, control the activity of aging-related genes, promote tumor senescence, enhance mitochondrial function, maintain liver balance, and protect the gut microbiome from inflammatory attacks. Given the desirable physiochemical and gelling properties of ulvan, it would serve to improve the quality and shelf-life of food.