Gaschromatography/mass spectrometry analysis of degradation of ethylacetoacetate achieved in shake flask culture using a previously characterized yeast strain Tichosporon dermatis.

Public and regulatory interest regarding the presence of pharmaceutically active compounds in the environment its increasing adverse impact has increased in the recent years. Detection of a wide variety of pharmaceutical compounds in water environment has been a serious and growing concern in the last few decades. Understanding the biological degradation of pharmaceutical compounds is essential for accurately determining their ultimate environmental fate, conducting accurate risk assessments, and improving removal of such micro pollutants.  Present investigation was designed to accomplish biodegradation of ethylacetoacetate in shake flask culture using whole cells of previously isolated and identified yeast strain Trichosporon dermatis, from pharmaceutical effluents using enrichment culture technique. The strain was cultivated for two generations on an orbital shaker at 120 rpm at 28 ± 20C and the biomass was separated by centrifugation at 10,000 rpm for 20 mts. Normal saline washed cells were used in degradation carried out in Erlenmeyer flasks containing 500 ml of mineral medium containing ethylacetoacetate at standard conditions; wet cell weight= 20g/l; ethylacetoacetate concentration = 0.5% in mineral medium (w/v); time of biodegradation= 72 hrs; temperature= 28 ± 20C. Gas chromatography/mass spectrometry (GC-MS) analysis of microbially degraded product revealed that complete degradation of ethylacetoacetate in mineral medium was achieved in 72 hours using whole cells of Trichosporon dermatis yeast strain. Degradation of ethylacetoacetate by this yeast strain has not been reported before the present investigation. Keywords: ethyl acetoacetate, biodegradation, Gass chromatography/mass spectrometry and effluents

Anti-uropathogenic activity, drug likeness, physicochemical and molecular docking assessment of (E-)-N′-(substituted-benzylidene)-2-(quinolin-8-yloxy) acetohydrazide

Objective: To deal with the anti-uropathogenic and in silico screening of (E-)-N′-(substituted-benzylidene)-2-(quinolin-8-yloxy)acetohydrazide analogues in order to search the potential anti-uropathogenic agents. Methods: Three (E-)-N′-(substituted-benzylidene)-2-(quinolin-8-yloxy)acetohydrazide analogues were synthesized. Structure elucidation was done using various spectroscopic techniques including infrared radiation, 1hydrogen-nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, etc. Physicochemical score, bioactivity score and molecular docking studies were carried out using Lipinski's rule of five, Molinspiration (web based software), Autodock 4.2 tools. In vitro anti-uropathogenic activity was carried out against four pathogens named as Staphylococcus aureus (S. aureus), Staphylococcus epidermidis, Proteus mirabilis and Escherichia coli by disc diffusion method and macro-dilution test following their morphological and biochemical characterization. Results: The formation of (E-)-N′-(substituted-benzylidene)-2-(quinolin-8-yloxy)acetohydrazide is confirmed from the spectroscopic results. All the compounds were found in compliance with Lipinski's rule of five and exhibited bioactivity score from −0.50 to 0.00. Docking results revealed that compound-1 is forming one hydrogen bond with TYR 576 and two hydrogen bond with GLU 569, while compound-2 is forming one hydrogen bond with ARG 599, and compound-3 forming 0 hydrogen bond. The anti-uropathogenic evaluation exhibited that compound one exhibited better activity against S. aureus, while it was found to possess moderate to good activity against both Gram-positive bacteria and Gram-negative bacteria excluding S. aureus. Conclusions: Our study revealed that compound one exhibited better activity than the standard in case of S. aureus and moderate to good activity against rest of the pathogens. Molecular docking, physicochemical and bioactivity studies strongly supported the experimental results. From the well obtained results it was concluded that compound-1 can lead as potential anti-uropathogenic agents

Antileishmanial screening, physicochemical properties and drug likeness of pyrazole carbaldehyde derivatives

Antileishmanial activities of the five pyrazole derivatives were evaluated in vitro on a culture of Leishmania donovani promastigotes (Strain S1). The results for Antileishmanial activity were compared with the standard drug Amphotericin B. Compound three and four were found to possess good activity than the standard drug. All the compounds were characterized by various spectroscopic techniques such as IR, 1H-NMR, 13C-NMR etc. Physicochemical properties and bioactivity score studies were carried out using Lipinski’s rule of five, Molinspiration (web based software). The results of computational studies found in accordance with the results obtained experimentally

An Approach for Systems-Level Understanding of Prostate Cancer from High-Throughput Data Integration to Pathway Modeling and Simulation

To understand complex diseases, high-throughput data are generated at large and multiple levels. However, extracting meaningful information from large datasets for comprehensive understanding of cell phenotypes and disease pathophysiology remains a major challenge. Despite tremendous advances in understanding molecular mechanisms of cancer and its progression, current knowledge appears discrete and fragmented. In order to render this wealth of data more integrated and thus informative, we have developed a GECIP toolbox to investigate the crosstalk and the responsible genes’/proteins’ connectivity of enriched pathways from gene expression data. To implement this toolbox, we used mainly gene expression datasets of prostate cancer, and the three datasets were GSE17951, GSE8218, and GSE1431. The raw samples were processed for normalization, prediction of differentially expressed genes, and the prediction of enriched pathways for the differentially expressed genes. The enriched pathways have been processed for crosstalk degree calculations for which number connections per gene, the frequency of genes in the pathways, sharing frequency, and the connectivity have been used. For network prediction, protein–protein interaction network database FunCoup2.0 was used, and cytoscape software was used for the network visualization. In our results, we found that there were enriched pathways 27, 45, and 22 for GSE17951, GSE8218, and GSE1431, respectively, and 11 pathways in common between all of them. From the crosstalk results, we observe that focal adhesion and PI3K pathways, both experimentally proven central for cellular output upon perturbation of numerous individual/distinct signaling pathways, displayed highest crosstalk degree. Moreover, we also observe that there were more critical pathways which appear to be highly significant, and these pathways are HIF1a, hippo, AMPK, and Ras. In terms of the pathways’ components, GSK3B, YWHAE, HIF1A, ATP1A3, and PRKCA are shared between the aforementioned pathways and have higher connectivity with the pathways and the other pathway components. Finally, we conclude that the focal adhesion and PI3K pathways are the most critical pathways, and since for many other pathways, high-rank enrichment did not translate to high crosstalk degree, the global impact of one pathway on others appears distinct from enrichment

<i>Helicobacter pylori</i> (<i>H. pylori</i>) Infection-Associated Dyslipidemia in the Asir Region of Saudi Arabia

Objectives: H. pylori-associated dyslipidemia has been reported to be a major risk factor for atherosclerosis and coronary heart diseases. We aimed to investigate the association of the H. pylori infection with dyslipidemia. Methods: A retrospective case–control study was undertaken to evaluate H. pylori-associated dyslipidemia, where H. pylori-positive individuals were treated as the case group (n = 260) while H. pylori-negative individuals were considered as the control group (n = 250). The mean ± SD of the age of the patients included (n = 510) was 44.01 ± 13.58 years. Study subjects with a total cholesterol level of >5.17 mmol/L and/or a triglyceride level of >1.69 mmol/L and/or an LDL-C level of >2.59 mmol/L and/or an HDL-C level of t-test, chi-square test, and logistic regression) statistical analyses were undertaken using the R-base/R-studio (v-4.0.2)/tidyverse package. Univariate and bivariate logistic regressions were executed to calculate the crude and adjusted odds ratio along with the p-value. A p-value of H. pylori positive vs. negative) of the cholesterol (5.22 ± 1.0 vs. 5.49 ± 0.85, p p p p 60, age = 30–60, in females, and LDL-C levels in males were not significantly different for the H. pylori-positive and -negative groups. The proportion (H. pylori positive vs. negative) of hypercholesterolemia (190/59.9% vs. 127/40% p p p p p p p p H. pylori-infected individuals as compared with the H. pylori-uninfected group. Conclusion: Our results demonstrate that an enhanced risk of dyslipidemia is associated with the H. pylori infection, which can aggrandize the atherosclerosis process. The evaluation of temporal variation in the lipid profile in H. pylori-infected individuals is recommended for the effective management of H. pylori-infected patients