Unlocking the therapeutic potential of bioactive exopolysaccharide produced by marine actinobacterium Streptomyces vinaceusdrappus AMG31: A novel approach to drug development.

Acidic exopolysaccharide (EPS) was produced by a marine actinobacterium Streptomyces vinaceusdrappus strain AMG31 with the highest yield of 10.6 g/l. The synthesized EPS has an average molecular weight of 5.1 × 104 g/mol and contains arabinose, glucose, galacturonic acid (0.5:2:2 M ratio), with 39.77 % uronic acid residues and 18.8 % sulfate detected. EPS exhibited antioxidant activities with 93.8 % DPPH radical scavenging and 344.7 µg/mg total antioxidant capacity. It displayed anti-inflammatory effects by inhibiting 5-LOX and COX-2. Regarding the cytotoxic activity, the IC50 values are 301.6 ± 11.8, 260.8 ± 12.2, 29.4 ± 13.5, 351.3 ± 11.2, 254.1 ± 9.8, and 266.5 ± 10.4 µg/ml for PC-3, HEP-2, MCF-7, HCT-116, A-549, HepG-2 respectively, which indicate that the produced EPS does not have strong cytotoxic activities. Moreover, the EPS showed anti-Alzheimer activity via inhibition of the Butyrylcholinesterase enzyme, with the highest percentage of 84.5 % at 100 µg/ml. Interestingly, the EPS showed superior anti-obesity activity by inhibiting lipase enzyme with a rate of 95.3 % compared to orlistat as a positive control (96.8 %) at a concentration of 1000 µg/ml. Additionally, the produced EPS displayed the highest anti-diabetic properties by inhibiting α-amylase (IC50 31.49 µg/ml) and α-glucosidase (IC50 6.48 µg/ml), suggesting antidiabetic potential analogous to acarbose. EPS exhibited promising antibacterial and antibiofilm activity against a wide range of Gram-positive and Gram-negative pathogenic bacteria.

Association of IL-10-592 C > A /-1082 A > G and the TNFα -308 G > A with susceptibility to COVID-19 and clinical outcomes.

BACKGROUND: Variation in host immune responses to SARS-CoV-2 is regulated by multiple genes involved in innate viral response and cytokine storm emergence like IL-10 and TNFa gene polymorphisms. We hypothesize that IL-10; -592 C > A and - 1082 A > G and TNFa-308 G > A are associated with the risk of SARS-COV2 infections and clinical outcome. METHODS: Genotyping, laboratory and radiological investigations were done to 110 COVID-19 patients and 110 healthy subjects, in Ismailia, Egypt. RESULTS: A significant association between the - 592 A allele, A containing genotypes under all models (p < 0.0001), and TNFa A allele with risk to infection was observed but not with the G allele of the - 1082. The - 592 /-1082 CG and the - 592 /-1082/ -308 CGG haplotypes showed higher odds in COVID-19 patients. Severe lung affection was negatively associated with - 592, while positive association was observed with - 1082. Higher D-dimer levels were strongly associated with the - 1082 GG genotype. Survival outcomes were strongly associated with the GA genotype of TNFa. -308 as well as AGG and AAA haplotypes. CONCLUSION: IL-10 and TNFa polymorphisms should be considered for clinical and epidemiological evaluation of COVID-19 patients.

Proteomics and metabolomics analyses of Streptococcus agalactiae isolates from human and animal sources.

Streptococcus agalactiae (S. agalactiae), group B Streptococcus (GBS), a major cause of infection in a wide variety of diseases, have been compared in different human and animal sources. We aimed to compare the bacterial proteome and metabolome profiles of human and animal S. agalactiae strains to delineate biological interactions relevant to infection. With the innovative advancement in mass spectrometry, a comparative result between both strains provided a solid impression of different responses to the host. For instance, stress-related proteins (Asp23/Gls24 family envelope stress response protein and heat shock protein 70), which play a role in the survival of GBS under extreme environmental conditions or during treatment, are highly expressed in human and animal strains. One human strain contains ꞵ-lactamase (serine hydrolase) and biofilm regulatory protein (lytR), which are important virulence regulators and potential targets for the design of novel antimicrobials. Another human strain contains the aminoglycosides-resistance bifunctional AAC/APH (A0A0U2QMQ5) protein, which confers resistance to almost all clinically used aminoglycosides. Fifteen different metabolites were annotated between the two groups. L-aspartic acid, ureidopropionic acid, adenosine monophosphate, L-tryptophan, and guanosine monophosphate were annotated at higher levels in human strains. Butyric acid, fumaric acid, isoleucine, leucine, and hippuric acid have been found in both human and animal strains. Certain metabolites were uniquely expressed in animal strains, with fold changes greater than 2. For example, putrescine modulates biofilm formation. Overall, this study provides biological insights into the substantial possible bacterial response reflected in its macromolecular production, either at the proteomic or metabolomic level.

Genotyping of Helicobacter pylori Virulence Genes cagA and vacA: Regional and National Study.

Helicobacter pylori (H. pylori) plays a crucial role in the pathogenesis of gastritis, peptic ulcer, and gastric cancer. The presence of pathogenicity islands (PAI) genes contributes to the pathogenesis of many gastrointestinal disorders. Cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene (vacA) are the most known virulence genes in H. pylori. So, our aim was to study H. pylori virulence genes' role in gastric disorders pathogenesis. Our study included 150 adult patients who suffered dyspeptic symptoms and were referred to the GIT endoscopy unit. Gastric biopsies were attained for rapid urease test (RUT) and histopathological examination, and multiplex PCR technique for detection of virulence genes was performed. It was found that 100 specimens were (RUT) positive, of which sixty samples (60%) were PCR positive for H. pylori ureC gene. The vacA and cagA genes were identified in 61.6% and 53% of H. pylori strains, respectively. Only 5 cases were vacA-positive and cagA-negative. The most virulent vacA s1 allele existed in 56.6% of cases. Out of the 60 H. pylori strains, 66% had at least one virulence gene and 34% did not show any virulence gene. H. pylori infection showed significant increase with age. H. pylori are prevalent amid dyspeptic patients in our region. The main genotype combinations were vacA+/cagA+ of s1m1 genotype and they were frequently associated with peptic ulcer diseases, gastritis, and gastroesophageal reflux disease.