Identifying therapeutic antibacterial peptides against Vibrio cholerae to inhibit the function of Na(+)-translocating NADH-quinone reductase.

Vibrio cholerae is the bacteria responsible for cholera, which is a significant threat to many nations. Curing and treating this infection requires identification of the critical protein and development of a drug to inhibit its function. In this context, Na(+)-translocating NADH-quinone reductase was considered a potential therapeutic target. A library of antibacterial peptides with residue lengths of 50 was screened using a docking method, and the five most potent peptides were selected on the basis of a weighted score derived from solvent accessible surface area and docking score. To investigate the stability of the protein-peptide complex, a 100-ns molecular dynamics simulation was performed. These peptides targeted the native dimeric binding interface of Na(+)-transporting NADH-quinone reductase. This study evaluated the binding affinity and conformational stability of these peptides with the protein using different post-simulation metrics. A peptide, CCL28, exhibited steady RMSD characteristics; nonetheless, it modified the docked conformation but stabilized in the new conformation. This peptide also demonstrated the best performance in addressing the protein's native binding interface. It demonstrated a binding free energy of -120 kcal/mol with the protein. Principal component analysis (PCA) revealed that the first PC had the lowest conformational variation and the greatest coverage. Eventually, these peptides were also evaluated using steered molecular dynamics, and it was discovered that CCL28 had a greater maximum force than the other five peptides, at 1139.08 kJ/mol/nm. Targeting the native binding interface, we present a CCL28 peptide with a strong potential to block the biological activity of Vibrio cholerae's Na(+)-translocating NADH-quinone reductase.Communicated by Ramaswamy H. Sarma.

Phytochemical analysis and nephroprotective potential of Ajwa date in doxorubicin-induced nephrotoxicity rats: Biochemical and molecular docking approaches.

The purpose of this study is to evaluate the likely defensive impact of Ajwa date aqueous extract (AJDAE) in alleviating the nephrotoxicity generated by doxorubicin (DOX) injection in rats. Sixty male Wister albino rats were randomly and equally separated into six groups (n = 10), and they were treated as follows: untreated control group, extract groups administered with 0.75 and 1.5 mg kg bw of AJDAE, toxicant control group administered with DOX, and prophylactic groups were treated with 0.75 and 1.5 mg/kg of AJDAE and 15 mg/kg DOX. Biochemical parameters, antioxidant enzymes, renal functions, DNA integrity, and histopathology were studied to evaluate the nephroprotective activity of AJDAE. Furthermore, bioactive compounds were utilized for in silico molecular docking. AJDAE treatment resulted in significant improvements in the amended renal biomarkers (urea, creatinine, calcium, phosphorous, and uric acid), antioxidative markers, and MDA. Noticeable histopathological improvements supported this result. Results of in silico studies revealed that d-Mannitol, 6TMS derivative, palmitic acid, and TMS derivative had a higher docking score with human soluble epoxide hydrolase (-10.9 kcal/mol) and NF-κB-DNA (-7 kcal/mol). The present findings indicated that AJDAE could decrease ROS generation and lipid peroxidation (LPO) and repair the DOX injection-related DNA damage.

Tritium and radiocarbon in the water column of the Red Sea.

Despite being the busiest transient sea in the world due to the Suez Canal, radionuclide distribution studies in seawater and sediment of the Red Sea remain rare. A sampling expedition in the Red Sea was conducted from June 9 to July 6, 2021, visiting a transect of several deep sampling stations located along the central axis of the basin from the Gulf of Aqaba to the southern Red Sea (near Farasan Island, Saudi Arabia). The collected seawater profile samples were analyzed for tritium, radiocarbon and oxygen-18. The observed tritium levels in surface waters of the Red Sea peaked at 0.3-0.4 TU, similar to the values observed in the western Arabian Sea (decay corrected). The values observed at waters below 150 m were around 0.2 TU, however, at depths of 450 and 750 m, tritium minima (<0.2 TU) were observed, which could be associated with a partial return flow of bottom waters from the southern to the northern Red Sea. At two stations at the depth of about 550 m, deep Δ14C minima were observed as well (-4‰ and -10‰), documenting ongoing transport of carbon in the water column, important for sink of anthropogenic carbon.

Computational screening of natural compounds as putative quorum sensing inhibitors targeting drug resistance bacteria: Molecular docking and molecular dynamics simulations.

Quorum sensing (QS) is a bacterial communication strategy controlling cells density, biofilm formation, virulence, sporulation, and survival. Since QS is considered a virulence factor in drug-resistant pathogenic bacteria, inhibition of QS can contribute to control the spread of these bacteria. We propose in this study to test in silico, 19 natural compounds for their potential to inhibit QS transcriptional regulators of Pseudomonas aeruginosa (LasR and PqsE) and Chromobacterium violaceum (CviR and CviR'). Molecular docking was performed to explore the binding energies between selected compounds, and QS signaling proteins. Additionally, molecular dynamics (MD) simulations of the complexes protein-ligand were tested to evaluate the stability of the complexs throughout the simulation process. The simulation interaction diagram (SID) was achieved to compute the radius of gyration (rGyr), solvent accessible surface area (SASA), intramolecular HBs, molecular surface area (MolSA), and polar surface area (PSA). Additionally, the physicochemical properties, pharmacokinetics, drug-likeness, and toxicity analysis of the best-selected compounds were determined. Among these compounds, catechin and nakinadine B were identified as potent QS antagonists that showed the best XP GScore and stable interaction during molecular dynamic simulation. Catechin interacts with LasR and CviR' displaying XP GScore -10.969 kcal/mol and -9.936 kcal/mol respectively. Additionally, nakinadine B interacts with PqsE and CviR giving XP GScore -7.442 kcal/mol and -10.34 kcal/mol respectively. RMSD plot analysis showed that both catechin and nakinadine B were stable during 50 ns simulation time with the tested target proteins. The predictive result of toxicity demonstrated that catechin and nakinadine B doesn't induce cytotoxicity, immunotoxicity, carcinogenicity, mutagenicity, hepatotoxicity and were at medium risk for hERG inhibition. Also they were found to be inactive for androgen receptor and aromatase. These results imply that catechin and nakinadine B may be suggested as QS modulators, which may reduce the virulence factors of drug-resistant bacteria.

Potential antitumor activity of exopolysaccharide produced from date seed powder as a carbon source for Bacillus subtilis.

The major functions of Exopolysaccharide (EPS) include, preventing bacterial cells from desiccating and biofilm production to increase the colonization of bacterial cells. In the current study, a bacterial strain was isolated to produce EPS. Phylogenetic analysis of the isolated strain indicated it was related to Bacillus subtilis. The bacterium showed the ability to produce a new EPS using very cheap date seeds as a carbon source. Different conditions were studied to enhance exopolysaccharide production. Maximum total sugars (exopolysaccharide) were reached to 0.87 mM) at 20 g/lAjwadates seed (ADS). The maximum production was found to be 3.46 mM by addition of peptone as the main source of nitrogen with a concentration of 1.5 g/L. The optimal parameter values were temperature 37 °C, pH 6, incubation time 72 h and inoculum concentration 1 mL. The crude exopolysaccharide was purified by removing the cells, then the protein, then dialysis and finally ethanol precipitation of the exopolysaccharide. This method modification increased exopolysaccharide production to 0.6 g/L. The exopolysaccharide produced showed antitumor activity against Erlich tumor cells. It is promising for application on a large scale for different types of cancer cell lines.

Amelioration of CCl4-Induced Hepatotoxicity in Rabbits by Lepidium sativum Seeds.

The current study aimed to evaluate the probable protective effect of Lepidium sativum seeds (LSS) against CCl4 induced hepatic injury in New-Zealand rabbits. Rabbits were randomly divided into two main groups; group-A (noninjured group, n=15) was divided to subgroups A1 (untreated control) and A2 and A3 which received 200 & 400 mg/kg bw of LSS, respectively, in their diet daily. Group-B (injured group, n=30) were subcutaneously injected with CCl4 (0.5 ml/kg bw) starting from day one of the experiment and were equally divided into 3 subgroups: B1 received normal standard diet and B2 & B3 received 200 & 400 mg/kg bw of LSS, respectively, in their diet daily. Five rabbits of all subgroups were decapitated 5 and 10 weeks after experimental running. Biochemical analysis revealed significant decrease in serum levels of transaminases, γ-GT, ALP, total bilirubin, cholesterol, triglycerides associated with significant increase in the serum levels of T protein and albumin of 200 and 400 mg/kg bw of LSS protected rabbits for 5 and 10 weeks as compared with CCl4 treated rabbits. Oxidative stress and depressed antioxidant system of the liver tissues were markedly obvious in the CCl4 treated group. LSS administration reversed these results towards normalization. Histopathological examination of LSS protected rabbits (200 mg/kg bw of LSS for 10 weeks) showed improvement of the histoarchitectural changes of the liver induced by CCl4 to the normal aspect, showing regenerating hepatocytes with no steatosis, discrete chronic venous congestion, and discrete inflammatory infiltrate. The current findings provide new evidence that LSS could reverse the hepatotoxic effects of CCl4 and repair the liver functions.

Identification of variants in the mitochondrial lysine-tRNA (MT-TK) gene in myoclonic epilepsy-pathogenicity evaluation and structural characterization by in silico approach.

Variations in mitochondrial genes have an established link with myoclonic epilepsy. In the present study we evaluated the nucleotide sequence of MT-TK gene of 52 individuals from 12 unrelated families and reported three variations in 2 of the 13 epileptic patients. The DNA sequences coding for MT-TK gene were sequenced and mutations were detected in all participants. The mutations were further analyzed by the in silico analysis and their structural and pathogenic effects were determined. All the investigated patients had symptoms of myoclonus, 61.5% were positive for ataxia, 23.07% were suffering from hearing loss, 15.38% were having mild to severe dementia, 69.23% were males, and 61.53% had cousin marriage in their family history. DNA extracted from saliva was used for the PCR amplification of a 440 bp DNA fragment encompassing complete MT-TK gene. The nucleotide sequence analysis revealed three mutations, m.8306T>C, m.8313G>C, and m.8362T>G that are divergent from available reports. The identified mutations designate the heteroplasmic condition. Furthermore, pathogenicity of the identified variants was predicted by in silico tools viz., PON-mt-tRNA and MitoTIP. Secondary structure of altered MT-TK was predicted by RNAStructure web server. Studies by MitoTIP and PON-mt-tRNA tools have provided strong evidences of pathogenic effects of these mutations. Single nucleotide variations resulted in disruptive secondary structure of mutant MT-TK models, as predicted by RNAStructure. In vivo confirmation of structural and pathogenic effects of identified mutations in the animal models can be prolonged on the basis of these findings.

Atorvastatin Treatment Modulates the Gut Microbiota of the Hypercholesterolemic Patients.

Hypercholesterolemia is one of the most important risk factors for development of cardiovascular diseases. The composition of gut microbiota (total microbes residing in the gut) impacts on cholesterol and lipid metabolism. On the contrary, alterations in gut microbiota in response to hypercholesterolemia or drug treatment with atorvastatin (a cholesterol-lowering agent) are rarely investigated. We performed 16S rDNA amplicon sequencing to evaluate the gut bacterial community of 15 untreated hypercholesterolemic patients (HP) and 27 atorvastatin-treated hypercholesterolemic patients (At-HP) and compared with 19 healthy subjects (HS). In total, 18 different phyla were identified in the study groups. An increase in relative abundance of Proteobacteria was observed in the HP group compared with At-HP and HS groups. The atherosclerosis-associated genus Collinsella was found at relatively higher abundance in the HP group. The anti-inflammation-associated bacteria (Faecalibacterium prausnitzii, Akkermansia muciniphila, and genus Oscillospira) were found in greater abundance, and proinflammatory species Desulfovibrio sp. was observed at decreased abundance in the drug-treated HP group compared with the untreated HP group. Relative abundances of the Bilophila wadsworthia and Bifidobacterium bifidum (bile acid-associated species) were decreased in the At-HP group. The At-HP and HS clustered separately from HP in the principal coordinate analysis. Decreased bacterial diversity was observed in the atorvastatin-treated group. In conclusion, these data suggest that atorvastatin treatment of patients with hypercholesterolemia may selectively restore the relative abundance of several dominant and functionally important taxa that were disrupted in the HP. Further studies are required to investigate the putative modifying effects of hypocholesterolemic drugs on functionality of gut microbiota, and the potential downstream effects on human health.

Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats.

The aim of the present study was to investigate alterations in gut microbiota associated with hypercholesterolemia and treatment with atorvastatin, a commonly prescribed cholesterol-lowering drug. In this study, seven experimental groups of rats were developed based on diets [high-fat diet (HFD) and normal chow diet (NCD)] and various doses of atorvastatin in HFD and NCD groups. 16S rRNA amplicon sequencing was used to analyze the gut microbiota. Atorvastatin significantly reduced the cholesterol level in treated rats. Bacterial diversity was decreased in the drug-treated NCD group compared to the NCD control, but atorvastatin-treated HFD groups showed a relative increase in biodiversity compared to HFD control group. Atorvastatin promoted the relative abundance of Proteobacteria and reduced the abundance of Firmicutes in drug-treated HFD groups. Among the dominant taxa in the drug-treated HFD groups, Oscillospira, Parabacteroides, Ruminococcus, unclassified CF231, YRC22 (Paraprevotellaceae), and SMB53 (Clostridiaceae) showed reversion in population distribution toward NCD group relative to HFD group. Drug-treated HFD and NCD groups both showed an increased relative abundance of Helicobacter. Overall, bacterial community composition was altered, and diversity of gut microbiota increased with atorvastatin treatment in HFD group. Reversion in relative abundance of specific dominant taxa was observed with drug treatment to HFD rats.

Characterization of Salmonella enterica serovar Typhimurium aconitase A.

Aconitases (Acn) are iron-sulfur proteins that catalyse the reversible isomerization of citrate and isocitrate via the intermediate cis-aconitate in the Krebs cycle. Some Acn proteins are bi-functional and under conditions of iron starvation and oxidative stress lose their iron-sulfur clusters and become post-transcriptional regulators by binding specific mRNA targets. Many bacterial species possess two genetically distinct aconitase proteins, AcnA and AcnB. Current understanding of the regulation and functions of AcnA and AcnB in dual Acn bacteria is based on a model developed in Escherichia coli. Thus, AcnB is the major Krebs cycle enzyme expressed during exponential growth, whereas AcnA is a more stable, stationary phase and stress-induced enzyme, and both E. coli Acns are bi-functional. Here a second dual Acn bacterium, Salmonella enterica serovar Typhimurium (S. Typhimurium), has been analysed. Phenotypic traits of S. Typhimurium acn mutants were consistent with AcnB acting as the major Acn protein. Promoter fusion experiments indicated that acnB transcription was ~10-fold greater than that of acnA and that acnA expression was regulated by the cyclic-AMP receptor protein (CRP, glucose starvation), the fumarate nitrate reduction regulator (FNR, oxygen starvation), the ferric uptake regulator (Fur, iron starvation) and the superoxide response protein (SoxR, oxidative stress). In contrast to E. coli, S. Typhimurium acnA was not induced in the stationary phase. Furthermore, acnA expression was enhanced in an acnB mutant, presumably to partially compensate for the lack of AcnB activity. Isolated S. Typhimurium AcnA protein had kinetic and mRNA-binding properties similar to those described for E. coli AcnA. Thus, the work reported here provides a second example of the regulation and function of AcnA and AcnB proteins in a dual Acn bacterium.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 June 2011-31 July 2011.

This article documents the addition of 112 microsatellite marker loci and 24 pairs of single nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Agelaius phoeniceus, Austrolittorina cincta, Circus cyaneus, Circus macrourus, Circus pygargus, Cryptocoryne × purpurea Ridl. nothovar. purpurea, Mya arenaria, Patagioenas squamosa, Prochilodus mariae, Scylla serrata and Scytalopus speluncae. These loci were cross-tested on the following species: Cryptocoryne × purpurea nothovar. purpurea, Cryptocoryne affinis, Cryptocoryne ciliata, Cryptocoryne cordata var. cordata, Cryptocoryne elliptica, Cryptocoryne griffithii, Cryptocoryne minima, Cryptocoryne nurii and Cryptocoryne schulzei. This article also documents the addition of 24 sequencing primer pairs and 24 allele-specific primers or probes for Aphis glycines.

Barriers to sexual activity: counselling spinal cord injured women in Malaysia.

STUDY DESIGN: This study is a cross-sectional, face-to-face interview. OBJECTIVES: To examine the sexual activity in a sample of Malaysian women with traumatic spinal cord injuries (SCIs), identify the physical and psychological barriers to it, and explore their experiences with sexual counseling and rehabilitation. SETTING: This study was conducted at the Spinal Rehabilitation Unit of a teaching hospital. METHODS: All women who attended scheduled check-ups, over 1 year, and who met the inclusion criteria (age above 18 years, spinal injury of traumatic aetiology, living in the community and having completed the rehabilitation) were consecutively included in a face-to-face interview using a self-constructed questionnaire. Sociodemographic and disability-related variables, barriers to sexual activity/satisfaction and experiences of sexual rehabilitation services were obtained. RESULTS: During the study period, 33/36 subjects were recruited. Although 67% indicated interest in sexual activity, only 24% was sexually active. The frequency of sexual activity declined after the injury, from 4.6 times per month to 1.5 times per month. Feeling unattractive, unable to satisfy the partner and less confident about sexual ability were top three psychological barriers to sexual activity, and the top three physical barriers were impaired genital sensation, positioning and vaginal lubrication. In all, 50% received some sexual information during rehabilitation. Rehabilitation professionals were expected to initiate sexual counseling by 62.5% of subjects. CONCLUSION: The effect of SCIs on sexual function is tremendous. Sexual counseling services must be improved and take into account the impact of psychological factors.

Soft-tissue recurrence of giant cell tumor of bone associated with pulmonary metastases.

A soft tissue recurrence associated with pulmonary metastases developed in a 46 year old lady one year after intra-lesional excision and autogenous bone graft of giant cell tumor of bone of the distal end of the right radius. The different imaging modalities and procedures used for staging as well as the management were discussed. Brief review of relevant literatures addressed different factors that influence addressed different factors that influence recurrence, treatment Options of primary and recurrent GCT of distal radius, and metaplastic recurrent GCT of distal radius, and metaplastic bone formation in such lesions.

Relationship between indoor environmental physical factors and depression aspects.

The relationship between various physical indoor environmental factors and the level of the studied depression aspects had been investigated. The study has been tried to involve patients suffering from different levels of depression and treated at specialized mental hospitals. Significant negative correlation had established been the between efficient indoor physical environment such as available basic home facilities, ventilation and sunny environment, home satisfaction, neighborhood physical environment and work physical environment, and the increased levels of depression aspects namely, physiological, attitude, behavior, social, situational, self satisfaction and self insight of depression. Recommendations were advised to add improvement of indoor physical environment to the line of depression treatment and to evaluate the efficiency of improving the work physical environment and its outcome in improving the physical and mental health of the workers with expected increased productivity and efficiency of the exposed workers.