Differently substituted flavanones were isolated from Leguminosae and their antibacterial activity was comparatively studied against methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MICs) of phytochemical flavanones to clinical isolates of MRSA were determined by a serial agar dilution method. The structure-activity relationship has indicated that 2',4'- or 2',6'-dihydroxylation of the B ring and 5,7-dihydroxylation of the A ring in the flavanone structure are important for significant anti-MRSA activity and that substitution with a certain aliphatic group at the 6- or 8-position also enhances the activity. Among the thirteen flavanones tested, tetrahydroxyflavanones with these structural characteristics isolated from Sophora exigua and Echinosophora koreensis showed intensive activity to inhibit the growth of all MRSA strains at 3.13-6.25 micrograms/ml. The present hydroxyflavanones would be useful in the phytotherapeutic strategy against MRSA infections.

Comparative Study on the Antibacterial Activity of Phytochemical Flavanones against Methicillin-resistant Staphylococcus aureus.

Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA-B*57:01, is associated with increased risk of a hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ~6% of patients and can be life-threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B genotype.

/pdf/clinical-pharmacogenetics-implementation-consortium-1sqjyx0b7f.pdf

Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and carbamazepine dosing

Diabetes mellitus is a non-communicable disease that occurs in both developed and developing countries. This metabolic disease affects all systems in the body, including the liver. Hyperglycaemia, mainly caused by insulin resistance, affects the metabolism of lipids, carbohydrates and proteins and can lead to non-alcoholic fatty liver disease, which can further progress to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinomas. The underlying mechanism of diabetes that contributes to liver damage is the combination of increased oxidative stress and an aberrant inflammatory response; this activates the transcription of pro-apoptotic genes and damages hepatocytes. Significant involvement of pro-inflammatory cytokines-including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α-exacerbates the accumulation of oxidative damage products in the liver, such as malondialdehyde, fluorescent pigments and conjugated dienes. This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals.

/pdf/mechanisms-of-diabetes-induced-liver-damage-the-role-of-4wqdr0tczl.pdf

Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation

Blastocystis is a common parasite of the human large intestine but has an uncertain role in disease. In this review, we appraise the published evidence addressing this and its weaknesses. Genetic diversity studies have led to the identification of numerous subtypes (STs) within the genus Blastocystis and, recently, methods for studying variation within STs have been developed, with implications for our understanding of host specificity. The geographic distribution of STs is summarised and the impact this may have on investigations into the role of the organism in disease is discussed. Finally, we describe the organelle and nuclear genome characteristics and look to future developments in the field.

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Recent developments in Blastocystis research.

More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides. Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties. Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases.

Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans

Hepatic glucose production (HGP) is regulated by a complex system of hormones, receptors, signaling mechanisms, glycolytic and gluconeogenic enzymes, and many overlapping transcription factors. The proteins involved in HGP are attractive targets for antidiabetic therapy, and thus it is critical to identify and characterize new targets within the regulation of HGP. We identified a novel peptide, neuronostatin (NST), encoded in the somatostatin preprohormone that exerts its effects in the central nervous system, the heart, and the pancreas. NST is produced in the delta cells of the pancreatic islets and plays an important role in maintaining glucose homeostasis through enhancing glucagon secretion from the α cell and reducing insulin release from the β cell. In male rats, a bolus injection of NST significantly increased blood glucose over 30 minutes after administration. Likewise, the peptide delayed glucose clearance and diminished the insulin response to hyperglycemia in a glucose tolerance test. Our group also identified the orphan GPCR, GPR107, as a cognate receptor for the peptide. GPR107 is expressed in numerous tissues, including the liver. In searching for the role of NST in hepatic physiology, we observed that hepatocellular carcinoma cell line HEPG2 expressed GPR107. Thus, we hypothesized that NST would elicit hepatic glucose production. We found that treatment of HEPG2 cells with NST significantly elevated cFos mRNA expression, indicating that HEPG2 cells respond to the peptide. In addition, NST induced expression of key gluconeogenic enzymes and enhanced glucose release in HepG2 cells. In vivo, antagonism of the glucagon receptor in rats did not attenuate elevated blood glucose levels in response to treatment of NST, supporting a direct, glucagon-independent action of NST on HGP. Thus, our results suggest that NST could play a physiologically relevant role in the liver and that GPR107 could be a potential new target to modulate HGP. National Institute of Health (NIH) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neuronostatin induces gluconeogenic enzyme expression and glucose release in hepatocytes

Hydroxy benzoic acid derivatives are an important scaffold in medicinal chemistry. A review of the literature revealed that they have a wide range of biological activities, including anti-inflammatory, antibacterial, and anti-tumor properties. The current study aimed to synthesize three new hydroxy benzoic acid derivatives (compounds 8, 9, and 10) and test them as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in silico and in vitro. Traditional organic synthesis methods were applied to produce these compounds. Docking studies revealed that compound 8 had nearly equal binding energy (DG) to erlotinib, the standard EGFR tyrosine kinase inhibitor. -8.56 and -8.75 kcal/mol, respectively. Using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) viability assay, the cytotoxicity of the new hydroxy benzoic acid derivatives was tested against DLD-1 colorectal adenocarcinoma cells, HeLa cervical cancer cells, and MCF-7 breast cancer cells. Compound 8 showed cytotoxicity against the three cancer cell lines tested (25.05, 23.88, and 48.36 µM, respectively), while compound 9 showed cytotoxicity against HeLa cells only (37.67 µM), and compound 10 was cytotoxic to DLD-1 and HeLa cells (27.26 and 19.19 µM, respectively. The half maximal inhibitory concentrations (IC50) of compound 8 were comparable to those of the standard tyrosine kinase inhibitor drug erlotinib (13.86, 36.41, and 87.34 µM, respectively). In conclusion, the findings of the present study indicate that compound 8, through its EGFR inhibitory activity, is a promising cytotoxic agent.

https://tjphs.tu.edu.iq/index.php/j/article/download/371/356

Synthesis, Docking Study, and Cytotoxicity Evaluation of New Hydroxy benzoic Acid Derivatives

Background: SARS-coronavirus 2 is the causative of the COVID-19 pandemic. (SARS-COV-2). There is a correlation between illness severity and cytokines of proinflammation such as interleukin-6 (IL-6). The amount of COVID-19 cytokine produced might be affected by polymorphisms in the regulatory areas in genes of cytokine. In this study, an Iraqi population was used to investigate a possible connection between three IL-6 promoter SNPs and COVID-19 susceptibility. Methods: The goal of this cohort study required the participation of a total of 97 individuals, 52 of whom had been diagnosed with severe COVID-19 and 45 of whom had been diagnosed with intermediate COVID-19. In order to determine the genotypes of three selected SNPs in the promoter region of the IL-6 gene, genomic DNA was extracted from the peripheral blood leukocytes of patients utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. This was done in order to establish a baseline for future research. These single nucleotide polymorphisms were denoted by the SNP names rs13306435 (T > A), rs2069860 (A > T), and rs2069830 (A > T). Results: There were no significant changes seen in the genotype or allele distribution of chosen SNPs of IL-6 gene in the promoter region between patients with severe levels of COVID-19 and patients with moderate levels of COVID-19. These SNPs included rs13306435 (-395 T > A), rs2069860 (-632A > T), and rs2069830 (-612A > T). Conclusion: According to the results of our investigation, these SNPs do not seem to be linked with the severity of COVID-19 in the Arabian community in Iraq.

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Role of SNPs of IL6 gene in the incidence and progression of COVID19 patients in Wasit province

BACKGROUND
1,3,4-oxadizole and pyrazole derivatives, are very important scaffold for medicinal chemistry. Literature survey revealed that they possess wide spectrum of biological activities among which are anti-inflammatory and antitumor.


OBJECTIVES
To describe the synthesis and evaluation of two classes of new niflumic acid (NF) derivatives, the 1,3,4-oxadizole derivatives (compounds 4AE) and pyrazole derivatives (compounds 5 and 6) as EGFR tyrosine kinase inhibitors in silico and in vitro.


METHODS
The designed compounds were synthesized using conventional organic synthesis methods. The antitumor activities of the new NF derivatives against HepG2 hepatocellular carcinoma and A549 non-small cell lung cancer cell lines were assessed in vitro via MTT assay, flow cytometry, RT-PCR, as well as via molecular docking studies.


RESULTS
The cytotoxicity results indicated that the newly synthesized NF derivatives were cytotoxic against the two cancer cell lines, with compound 6 being the most cytotoxic, achieving the lowest IC50 concentration. Furthermore, compound 6 targeted EGFR tyrosine kinase leading to cell cycle arrest at the G2/M cell cycle phase, and induction of apoptosis. The in vitro biological investigation results matched those of the molecular docking analysis. In conclusion, the new NF derivatives, specifically compound 6, exhibited favorable pharmacokinetic features and are promising EGFR tyrosine kinase inhibitors.


CONCLUSION
A series of niflumic acid derivatives (3, 4A-E, 5 and 6) were successfully created and FT-IR, 1H, 13CNMR, and HRMS were used to confirm their chemical structures. According to molecular docking studies, compounds 3, 5, and 6 have the highest docking scores (ΔG) and the majority of the tested compounds have a good pharmacokinetic profile. Results of compound 6 in vitro antitumor activities show that it is a promising EGFR tyrosine kinase inhibitor.

A. A. Mahmood

Papers

Neuronostatin induces gluconeogenic enzyme expression and glucose release in hepatocytes

Synthesis, Docking Study, and Cytotoxicity Evaluation of New Hydroxy benzoic Acid Derivatives

Role of SNPs of IL6 gene in the incidence and progression of COVID19 patients in Wasit province

New Niflumic Acid Derivatives as EGFR Inhibitors: Design, Synthesis, In Silico Studies, and Anti-proliferative Assessment.