Assessment of the hypoglycemic and anti-hemostasis effects of Paederia foetida (L.) in controlling diabetes and thrombophilia combining in vivo and computational analysis.

Paederia foetida is valued for its folk medicinal properties. This research aimed to assess the acute toxicity, hypoglycemic and anti-hemostasis properties of the methanolic extract of P. foetida leaves (PFLE). Acute toxicity of PFLE was performed on a mice model. Hypoglycemic and anti-hemostasis properties of PFLE were investigated on normal and streptozotocin-induced mice models. Deep learning, molecular docking, density functional theory, and molecular simulation techniques were employed to understand the underlying mechanisms through in silico study. Oral administration of PFLE at a dosage of 300 µg/kg body weight (BW) showed no signs of toxicity. Treatment with PFLE (300 µg/kg/BW) for 14 days resulted in a hypoglycemic condition and a 30.47% increase in body weight. Additionally, PFLE mixed with blood exhibited a 44.6% anti-hemostasis effect. Deep learning predicted the inhibitory concentration (pIC50, nM) of Cleomiscosins against SGLT2 and FXa to be 7.478 and 6.017, respectively. Molecular docking analysis revealed strong binding interactions of Cleomiscosins with crucial residues of the target proteins, exhibiting binding energies of -8.2 kcal/mol and -7.1 kcal/mol, respectively. ADME/Tox predictions indicated favorable pharmacokinetic properties of Cleomiscosins, and DFT calculations of frontier molecular orbitals analyzed the stability and reactivity of these compounds. Molecular simulation dynamics, principal component analysis and MM-PBSA calculation demonstrated the stable, compact, and rigid nature of the protein-ligand complexes. The methanolic PFLE exhibited significant hypoglycemic and anti-hemostasis properties. Cleomiscosin may have inhibitory properties for the development of novel drugs to manage diabetes and thrombophilia in the near future.

Targeted expression of bgl23-D, a dominant-negative allele of ATCSLD5, affects cytokinesis of guard mother cells and exine formation of pollen in Arabidopsis thaliana.

MAIN CONCLUSION: Targeted expression of bgl23-D, a dominant-negative allele of ATCSLD5, is a useful genetic approach for functional analysis of ATCSLDs in specific cells and tissues in plants. Stomata are key cellular structures for gas and water exchange in plants and their development is influenced by several genes. We found the A. thaliana bagel23-D (bgl23-D) mutant showing abnormal bagel-shaped single guard cells. The bgl23-D was a novel dominant mutation in the A. thaliana cellulose synthase-like D5 (ATCSLD5) gene that was reported to function in the division of guard mother cells. The dominant character of bgl23-D was used to inhibit ATCSLD5 function in specific cells and tissues. Transgenic A. thaliana expressing bgl23-D cDNA with the promoter of stomata lineage genes, SDD1, MUTE, and FAMA, showed bagel-shaped stomata as observed in the bgl23-D mutant. Especially, the FAMA promoter exhibited a higher frequency of bagel-shaped stomata with severe cytokinesis defects. Expression of bgl23-D cDNA in the tapetum with SP11 promoter or in the anther with ATSP146 promoter induced defects in exine pattern and pollen shape, novel phenotypes that were not shown in the bgl23-D mutant. These results indicated that bgl23-D inhibited unknown ATCSLD(s) that exert the function of exine formation in the tapetum. Furthermore, transgenic A. thaliana expressing bgl23-D cDNA with SDD1, MUTE, and FAMA promoters showed enhanced rosette diameter and increased leaf growth. Taken together, these findings suggest that the bgl23-D mutation could be a helpful genetic tool for functional analysis of ATCSLDs and manipulating plant growth.

Comparison of Magnetic Resonance Enterography Global Score (MEGS) with indices of Crohn's disease activity in South Asian population.

PURPOSE: Assessment of disease activity in Crohn's helps predict important clinical outcomes. Among the various modalities available to assess disease activity, magnetic resonance enterography (MRE) is considered a safe and reliable imaging option. Various MRE-based scoring systems have been developed to measure disease activity, one of which being the MRE global score (MEGS). We aimed to correlate MEGS with some of the important indices of Crohn's disease activity. METHODOLOGY: Crohn's disease patients referred for MRE were included in the study. Along with demographic profile and relevant investigations, MRE parameters related to MEGS were also assessed. RESULT: A total of 47 patients were recruited for the study. Their median age was 34 years (range 18-68 years), and male:female ratio was 16:31. There was modest positive correlation between MEGS and faecal calprotectin (r = 0.3, p = 0.04), CRP level (r = 0.34, p = 0.02) and Harvey Bradshaw index (r = 0.3, p = 0.043), respectively. However, there was strong correlation between segmental MEGS and Simple Endoscopic Score in those with terminal ileal disease (r = 0.81, p < 0.001). Mural thickness was the only MRE parameter that correlated with active disease (OR - 1.35, 95% CI 1.01, 1.81, p = 0.041) on multivariate analysis. There was moderate inter-observer agreement (Lin's r = 0.78, p < 0.001). CONCLUSION: MEGS showed modest correlation with indices of Crohn's disease activity which corroborates the complementary role of MRE in management of such patients.

Molecular identification and biological control of Ralstonia solanacearum from wilt of papaya by natural compounds and Bacillus subtilis: An integrated experimental and computational study.

Ralstonia solanacearum is a harmful pathogen that causes severe wilt disease in several vegetables. In the present study, we identified R. solanacearum from wilt of papaya by 16S rRNA PCR amplification. Virulence ability of R. solanacearum was determined by amplification of approximately 1500 bp clear band of hrpB gene. Further, in-vitro seed germination assay showed that R. solanacearum reduced the germination rate up to 26.21%, 34% and 33.63% of cucumber, bottle guard and pumpkin seeds, respectively whereas shoot and root growth were also significantly decreased. Moreover, growth inhibition of R. solanacearum was recorded using antibacterial compound from medicinal plant and antagonistic B. subtilis. Petroleum ether root extract of Rauvolfia serpentina showed highest 22 ± 0.04 mm diameter of zone of inhibition where methanolic extract of Cymbopogon citratus and ethanolic extract of Lantana camara exhibited 20 ± 0.06 mm and 20 ± 0.01 mm zone of inhibition against R. solanacearum, respectively. In addition, bioactive compounds of B. subtilis inhibited R. solanacearum growth by generating 17 ± 0.09 mm zone of inhibition. To unveil the inhibition mechanism, we adopted chemical-protein interaction network and molecular docking approaches where we found that, rutin from C. citratus interacts with citrate (Si)-synthase and dihydrolipoyl dehydrogenase of R. solanacearum with binding affinity of -9.7 kcal/mol and -9.5 kcal/mol while quercetin from B. subtillis interacts with the essential protein F0F1 ATP synthase subunit alpha of the R. solancearum with binding affinity of -6.9 kcal/mol and inhibit the growth of R. solanacearum. Our study will give shed light on the development of eco-friendly biological control of wilt disease of papaya.

Synthesis of FeS and FeSe nanoparticles from a single source precursor: a study of their photocatalytic activity, peroxidase-like behavior, and electrochemical sensing of H2O2.

Nanocrystalline FeS and FeSe compounds were prepared by solvothermal decomposition of a precursor complex [Fe(3)(µ(3)-O)(µ(2)-O(2)CCH(2)Cl)(6)(H(2)O)(3)]NO(3)·H(2)O in the presence of thiourea and sodium selenite, respectively. The as-obtained products were characterized by X-ray diffraction analysis (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and UV-vis spectroscopic techniques. Structural analyses revealed that the FeS and FeSe nanoparticles (NPs) are composed of needle-like and spherical particles, respectively. The FeS and FeSe NPs showed photocatalytic activity for the decomposition of rose bengal (RB) and methylene blue (MB) dyes under white light illumination. They also showed good catalytic activity toward oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H(2)O(2) and followed Michaelis-Menten kinetics. In addition, both FeS and FeSe NPs exhibited electrocatalytic activity toward reduction of hydrogen peroxide, which on immobilization on glassy carbon (GC) electrodes perform as amperometric sensors for detection of H(2)O(2). At pH 7.0, the FeS/GC showed a linear range for detection of H(2)O(2) from 5 to 140 µM, while for FeSe/GC the range was 5 to 100 µM.

Microbial profile and antibiotic sensitivity pattern in acute bacterial cholangitis.

INTRODUCTION: The changing antimicrobial sensitivity pattern of causative organisms poses a therapeutic challenge in treating patients with acute cholangitis. We therefore evaluated the microbial profile and sensitivity pattern to antibiotics in patients with acute bacterial cholangitis. METHODS: Data of patients above 18 years of age with acute bacterial cholangitis seen between January 2004 and March 2007 were retrospectively analyzed. The study was continued prospectively from April 2007 to December 2008. Data on clinical features, etiological and microbial profile and therapy, and patient outcomes were analyzed. In the prospective group, the antibiotic susceptibility patterns of organisms grown on bile and blood culture were also obtained. RESULTS: One hundred and eighty-five patients with acute cholangitis were studied. Choledocholithiasis (62.7%) and malignancy (29.2%) were the main predisposing factors. Bile culture was positive in 88 of 95 patients, and blood culture was positive in 47 of 178 (26.4%) patients. Bile cultures were predominantly polymicrobial (69.5%) in contrast to blood cultures (2.2%). E. coli was the predominant isolate in blood and bile. No growth was seen on anaerobic bile or blood cultures. The prospective group showed high resistance of E. coli to third generation cephalosporins and ciprofloxacin. CONCLUSIONS: Changing antimicrobial sensitivity patterns requires a revision of empiric antibiotic therapy policy in cholangitis.