Streptomyces avermitilis MICNEMA2022: a new biorational strain for producing abamectin as an integrated nematode management agent.

BACKGROUND: Abamectin (ABA) is considered a powerful insecticidal and anthelmintic agent. It is an intracellular product of Streptomyces avermitilis; is synthesized through complicated pathways and can then be extracted from mycelial by methanol extraction. ABA serves as a biological control substance against the root-knot nematode Meloidogyne incognita. This investigation is intended to reach a new strain of S. avermitilis capable of producing ABA effectively. RESULTS: Among the sixty actinobacterial isolates, Streptomyces St.53 isolate was chosen for its superior nematicidal effectiveness. The mycelial-methanol extract of isolate St.53 exhibited a maximum in vitro mortality of 100% in one day. In the greenhouse experiment, the mycelial-methanol extract demonstrated, for the second-stage juveniles (J2s), 75.69% nematode reduction and 0.84 reproduction rate (Rr) while for the second-stage juveniles (J2s), the culture suspension demonstrated 75.38% nematode reduction and 0.80 reproduction rate (Rr). Molecular identification for St.53 was performed using 16 S rRNA gene analysis and recorded in NCBI Genbank as S. avermitilis MICNEMA2022 with accession number (OP108264.1). LC-MS was utilized to detect and identify abamectin in extracts while HPLC analysis was carried out for quantitative determination. Both abamectin B1a and abamectin B1b were produced and detected at retention times of 4.572 and 3.890 min respectively. CONCLUSION: Streptomyces avermitilis MICNEMA2022 proved to be an effective source for producing abamectin as a biorational agent for integrated nematode management.

Synthesis of 1,3,5-Triazepines and Benzo[f][1,3,5]triazepines and Their Biological Activity: Recent Advances and New Approaches.

This review article discusses the recent progress in synthesizing seven-membered ring 1,3,5-triazepine and benzo[f][1,3,5]triazepine derivatives. These derivatives can be either unsaturated, saturated, fused, or separated. This review covers strategies and procedures developed over the past two decades, including cyclo-condensation, cyclization, methylation, chlorination, alkylation, addition, cross-coupling, ring expansions, and ring-closing metathesis. This review discusses the synthesis of 1,3,5-triazepine derivatives using nucleophilic or electrophilic substitution reactions with various reagents such as o-phenylenediamine, 2-aminobenzamide, isothiocyanates, pyrazoles, thiazoles, oxadiazoles, oxadiazepines, and hydrazonoyl chloride. This article systematically presents new approaches and techniques for preparing these compounds. It also highlights the biological importance of benzo[f][1,3,5]triazepine derivatives, which have been used as drugs for treating nervous system diseases. This review aims to provide researchers with the necessary information to create and develop new derivatives of these compounds as quickly as possible.

Is vacuum-assisted closure therapy the main culprit in right ventricular rupture after deep sternal wound infection?

Right ventricular rupture after deep sternal wound infection (DSWI) is a rare but fatal complication, and can occur with or without vacuum assisted closure (VAC) therapy. There is currently no strong evidence to suggest whether or not VAC therapy is a contributing factor to this complication. In total, 30 articles were retrieved and assessed through a systematic review strategy from 1953 to 2022. The keywords: 'vacuum assisted closure'; 'VAC'; 'negative pressure wound therapy'; 'deep sternal wound infection'; 'DSWI'; 'right ventricular rupture'; and 'cardiac rupture' were used in the search. Overall, 15 of the included articles satisfied the predefined eligibility criteria. Fatal right ventricular ruptures were reported in 18 (36%) out of 50 cases. In this article, the risk factors, mechanisms and management of right ventricular rupture are discussed. A novel view of the mechanism of VAC-associated right ventricular rupture is highlighted, with a focus on both pre- and intraoperative management.

Telocytes in Cutaneous Biology: A Reappraisal. / [Artículo traducido] Los telocitos en la biología cutánea: revaluación.

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions.

Telocytes in Cutaneous Biology: A Reappraisal.

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions.

Incredible affinity of Kattosh with PPAR-γ receptors attenuates STZ-induced pancreas and kidney lesions evidenced in chemicobiological interactions.

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin-induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti-inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ-induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator-activated receptor-gamma (PPAR, PDB ID: 3G9E), AMP-activated protein kinase (AMPK, PDB ID: 4CFH) and α-amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti-inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand-receptor interaction, ethyl α-d-glucopyranoside of Kattosh showed the highest affinity for the α-amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.

Production and optimization of bioplastic (Polyhydroxybutyrate) from Bacillus cereus strain SH-02 using response surface methodology.

BACKGROUND: Polyhydroxybutyrate (PHB) is a biopolymer formed by some microbes in response to excess carbon sources or essential nutrient depletion. PHBs are entirely biodegradable into CO2 and H2O under aerobic and anaerobic conditions. It has several applications in various fields such as medicine, pharmacy, agriculture, and food packaging due to its biocompatibility and nontoxicity nature. RESULT: In the present study, PHB-producing bacterium was isolated from the Dirout channel at Assiut Governorate. This isolate was characterized phenotypically and genetically as Bacillus cereus SH-02 (OM992297). According to one-way ANOVA test, the maximum PHB content was observed after 72 h of incubation at 35 °C using glucose and peptone as carbon and nitrogen source. Response surface methodology (RSM) was used to study the interactive effects of glucose concentration, peptone concentration, and pH on PHB production. This result proved that all variables have a significant effect on PHB production either independently or in the interaction with each other. The optimized medium conditions with the constraint to maximize PHB content and concentration were 22.315 g/L glucose, and 15.625 g/L peptone at pH 7.048. The maximum PHB content and concentration were 3100.799 mg/L and 28.799% which was close to the actual value (3051 mg/l and 28.7%). The polymer was identified as PHB using FTIR, NMR, and mass spectrometry. FT-IR analysis showed a strong band at 1724 cm- 1 which attributed to the ester group's carbonyl while NMR analysis has different peaks at 169.15, 67.6, 40.77, and 19.75 ppm that were corresponding to carbonyl, methine, methylene, and methyl resonance. Mass spectroscopy exhibited molecular weight for methyl 3- hydroxybutyric acid. CONCLUSION: PHB-producing strain was identified as Bacillus cereus SH-02 (OM992297). Under optimum conditions from RSM analysis, the maximum PHB content and concentration of this strain can reach (3100.799 mg/L and 28.799%); respectively. FTIR, NMR, and Mass spectrometry were used to confirm the polymer as PHB. Our results demonstrated that optimization using RSM is one of the strategies used for reducing the production cost. RSM can determine the optimal factors to produce the polymer in a better way and in a larger quantity without consuming time.

Cystic adrenal masses: spectrum of multimodality imaging features and pathological correlation.

Adrenal cystic lesions are generally rare and encompass a wide spectrum of benign and malignant entities. Increased utilisation of cross-sectional imaging has led to increased detection of incidentally discovered adrenal lesions. Many of these lesions are cystic or solid with cystic changes, and the majority are benign; however, some may represent malignant lesions and/or even metastases. Therefore, it is vital to characterise these lesions appropriately and follow-up with laboratory tests and imaging if necessary. Key imaging techniques include computed tomography (CT) and magnetic resonance imaging (MRI). Other supplemental imaging tools include metaiodobenzyl-guanidine (MIBG) scintigraphy and 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (FDG-PET). Accurate diagnosis of adrenal cystic lesions is crucial in guiding appropriate evaluation and management of these patients. This review highlights the clinical presentations, pathological and imaging features, and management of cystic adrenal lesions.

Dialysis attendance patterns and health care utilisation of Aboriginal patients attending dialysis services in urban, rural and remote locations.

BACKGROUND: Aboriginal people in the Northern Territory (NT) suffer the heaviest burden of kidney failure in Australia with most living in remote areas at time of dialysis commencement. As there are few dialysis services in remote areas, many Aboriginal people are required to relocate often permanently, to access treatment. Missing dialysis treatments is not uncommon amongst Aboriginal patients but the relationship between location of dialysis service and dialysis attendance (and subsequent hospital use) has not been explored to date. AIM: To examine the relationships between location of dialysis service, dialysis attendance patterns and downstream health service use (overnight hospital admissions, emergency department presentations) among Aboriginal patients in the NT. METHODS: Using linked hospital and dialysis registry datasets we analysed health service activity for 896 Aboriginal maintenance dialysis patients in the NT between 2008 and 2014. Multivariate linear regression and negative binomial regression analyses explored the associations between dialysis location, dialysis attendance and health service use. RESULTS: We found missing two or more dialysis treatments per month was more likely for Aboriginal people attending urban services and this was associated with a two-fold increase in the rate of hospital admissions and more than three-fold increase in ED presentations. However, we found higher dialysis attendance and lower health service utilisation for those receiving care in rural and remote settings. When adjusted for age, time on dialysis, region, comorbidities and residence pre-treatment, among Aboriginal people from remote areas, those dialysing in remote areas had lower rates of hospitalisations (IRR 0.56; P < 0.001) when compared to those who relocated and dialysed in urban areas. CONCLUSION: There is a clear relationship between the provision and uptake of dialysis services in urban, rural and remote areas in the NT and subsequent broader health service utilisation. Our study suggests that the low dialysis attendance associated with relocation and care in urban models for Aboriginal people can potentially be ameliorated by access to rural and remote models and this warrants a rethinking of service delivery policy. If providers are to deliver effective and equitable services, the full range of intended and unintended consequences of a dialysis location should be incorporated into planning decisions.

The possible protective role of pimpinella anisum oil versus selenium on aspartame induced changes in rat cerebellar cortex: histological, immunohistochemical and electron microscopic study.

Aspartame (ASP) is an artificial sweeter. Chronic use of ASP has a harmful effect on cerebellar cortex. Anisum oil and selenium (SE) are antioxidant substances. Therefore, the present study was performed to study the possible protective role of anisum oil versus selenium on aspartame-induced changes in rat cerebellar cortex. Rats were divided into four main groups. Group I (Control group). Group II received 250 mg/kg/day aspartame once daily for 2 months. Group III received 0.5 ml/kg/day anisum 2 h before aspartame administration. Group IV received 0.5 mg/kg/day selenium 2 h before aspartame administration. The administration of Asp for 2 months (group II) resulted in cerebellar histopathological changes in the form of deformed Purkinje and granule cells. Ultrastructurally, Purkinje cells had irregular nuclei, dilated cisternae of rough endoplasmic reticulum, dilated saccules of Golgi apparatus, mitochondria with destroyed cristae. In addition, granule cells appeared shrunken with irregular nuclei. Aspartame and anisum oil treated group (group III) showed partial improvement. Examination of ASP and SE treated group (group IV) showed that cerebellar cortex was nearly similar to control. In conclusion, Anisum oil and selenium could protect against ASP-induced cerebellar damage. The protective effect of selenium is better than anisum oil.

Tandem synthesis, cytotoxicity, and in silico study of new 1,3,4-oxadiazoles as potential thymidylate synthase inhibitors.

A new series of pyrrole-linked mono- and bis(1,3,4-oxadiazole) hybrids, attached to various arene units, was prepared using a two-step tandem protocol. Therefore, a benzohydrazide derivative was condensed with the appropriate aldehydes in ethanol at 80°C for 60-150 min to give the corresponding N-(benzoylhydrazones). Without isolation, the previous intermediates underwent intramolecular oxidative cyclization in dimethyl sulfoxide at 180°C for 90-200 min in the presence of chloramine trihydrate to afford the target hybrids. The cytotoxicity of all hybrids was examined in vitro against the MCF-7, HEPG2, and Caco2 cell lines. Arene-linked hybrids 4i and 4j, attached to p-nitro and p-acetoxy units, were the most potent ones, with IC50 values ranging from 5.47 to 8.80 and 12.75 to 21.22 µM, respectively, when tested on the above cell lines. At the tested concentrations of 5 and 7.5 µM, hybrid 4i inhibited thymidylate synthase (TS) with the best inhibition percentages of 72.3 and 91.3, whereas hybrid 4j displayed comparable inhibitory activity to the reference pemetrexed. Hybrid 4j had inhibition percentages of 62.7 and 82.6, whereas pemetrexed had inhibition percentages of 59.2 and 80.2, respectively. The capability of hybrids 4i and 4j as potential TS inhibitors is supported by molecular docking studies, while SwissADME predicts their efficacy as drug-like scaffolds.

An eye on the future for defeating hydrocephalus, ciliary dyskinesia-related hydrocephalus: review article.

Congenital hydrocephalus affects approximately one in 1000 newborn children and is fatal in approximately 50% of untreated cases. The currently known management protocols usually necessitate multiple interventions and long-term use of healthcare resources due to a relatively high incidence of complications, and many of them mostly provide a treatment of the effect rather than the cause of cerebrospinal fluid flow reduction or outflow obstruction. Future studies discussing etiology specific hydrocephalus alternative treatments are needed. We systematically reviewed the available literature on the effect of ciliary abnormality on congenital hydrocephalus pathogenesis, to open a discussion on the feasibility of factoring ciliary abnormality in future research on hydrocephalus treatment modalities. Although there are different forms of ciliopathies, we focused in this review on primary ciliary dyskinesia. There is growing evidence of association of other ciliary syndromes and hydrocephalus, such as the reduced generation of multiple motile cilia, which is distinct from primary ciliary dyskinesia. Data for this review were identified by searching PubMed using the search terms 'hydrocephalus,' 'Kartagener syndrome,' 'primary ciliary dyskinesia,' and 'immotile cilia syndrome.' Only articles published in English and reporting human patients were included. Seven studies met our inclusion criteria, reporting 12 cases of hydrocephalus associated with primary ciliary dyskinesia. The patients had variable clinical presentations, genetic backgrounds, and ciliary defects. The ependymal water propelling cilia differ in structure and function from the mucus propelling cilia, and there is a possibility of isolated non-syndromic ependymal ciliopathy causing only hydrocephalus with growing evidence in the literature for the association ependymal ciliary abnormality and hydrocephalus. Abdominal and thoracic situs in children with hydrocephalus can be evaluated, and secondary damage of ependymal cilia causing hydrocephalus in cases with generalized ciliary abnormality can be considered.

Expression Profile of CD10, BCL-2, p63, and EMA in the Normal Skin and Basal Cell Carcinomas: An Immunohistochemical Reappraisal.

BACKGROUND: Basal cell carcinoma (BCC) is common cutaneous malignancy. AIMS: To examine the expression patterns of CD10, p63, BCL-2, and epithelial membrane antigen (EMA) proteins in BCC. MATERIALS AND METHODS: We used immunohistochemistry to evaluate the expression pattern of these proteins in 45 BCC specimens and their adjacent normal skin. RESULTS: We found variations in the expression pattern of these proteins among normal skins and BCC. In normal skins, we found strong EMA cytoplasmic expression (adnexal structures). A strong nuclear p63 protein expression was found in basal and some suprabasal keratinocytes, external root sheath cells of the hair follicles, basal cells of the sebaceous glands, and in sweat glands.CD10 protein expression was seen in peri-adnexal mesenchymal spindle cells and myoepithelial cells of sweat glands.BCL-2 protein expression was confined to the basal cell keratinocytes, epidermal melanocytes, outer root sheath, and infundibulum of the hair follicle. In BCC, we found p63 (diffuse, strong nuclear staining), CD10 (focal, moderate cytoplasmic reactivity), and BCL-2 (focal, moderate cytoplasmic reactivity) protein expression in the neoplastic cells. BCC was consistently negative for EMA (except in areas of squamous differentiation). CONCLUSIONS: There is an altered expression of these proteins in BCC. The underlying molecular mechanisms are open to further investigations.

A unique primary structure of RDL (resistant to dieldrin) confers resistance to GABA-gated chloride channel blockers in the two-spotted spider mite Tetranychus urticae Koch.

The primary structure of the second transmembrane (M2) segment of resistant to dieldrin (RDL), an ionotropic γ-aminobutyric acid receptor (GABAR) subunit, and the structure-function relationships in RDL are well conserved among insect species. An amino acid substitution at the 2' position in the M2 segment (Ala to Ser or Gly) confers resistance to non-competitive antagonists (NCAs) of GABARs. Here, a cDNA encoding RDL was cloned from the two-spotted spider mite Tetranychus urticae Koch. Unlike insect homologs, native TuRDL has His at the 2' position (H305) and Ile at 6' (I309) in the M2 segment and is insensitive to NCAs. Single and multiple mutations were introduced in the M2 segment of TuRDL, and the mutant proteins were expressed in Xenopus oocytes and examined for the restoration of sensitivity to NCAs. The sensitivity of a double mutant (H305A and I309T in the M2 segment) was greatly increased but was still considerably lower than that of insect RDLs. We therefore constructed chimeric RDLs consisting of TuRDL and Drosophila melanogaster RDL and examined their sensitivities to NCAs. The results show that the N-terminal region containing the Cys-loop as well as the M2 segment confers functional specificity; thus, our current understanding of the mechanism underlying NCA binding to GABARs requires reappraisal.

Safety of Combination Immune Checkpoint Inhibitors Compared to Monotherapy; A Systematic Review and Meta-Analysis.

Combination immune checkpoint inhibitors (ICIs) achieved higher efficacy than monotherapy in many types of cancers. We searched PubMed, Scopus, and Cochrane databases for randomized phase II/III trials in cancer patients receiving combination ICIs vs. Monotherapy. Our search retrieved 934 records. Eight studies were found to be eligible for meta-analysis recruiting 2544 patients. Combined immunotherapy nivolumab plus ipilimumab was associated with statistically significant higher risk of all grade adverse events (AE), and discontinuation due to all grade AEs as compared to both ipilimumab or nivolumab. Although combination ICIs showed better oncological activity, it carried a higher risk of all grade irAEs.

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study.

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

Efficacy of F-100, diluted F-100, and infant formula as rehabilitation diet for infants aged < 6 months with severe acute malnutrition: a randomized clinical trial.

PURPOSE: To assess the efficacy and safety of F-100, diluted F-100 (F100D), and infant formula (IF) for dietary management in the rehabilitation phase of severe acute malnutrition (SAM) of infants aged under 6 months (u6m). METHODS: Double-blind randomized clinical trial was conducted to assess the efficacy and safety of F-100, F-100D, and IF at the Nutrition Rehabilitation Unit, icddr,b. Infants (n = 153) u6m with SAM were enrolled and randomly assigned to any of the three diets after stabilization. Two ml blood was collected on study days 1, 3, and 7 for measuring serum electrolytes, creatinine and osmolality, urine samples for specific gravity and osmolality creatinine ratio. Renal Solute Load (RSL) and Potential Renal Solute Load (PRSL) were calculated. Infants were discharged when gained 15% of the admission bodyweight or had edema-free weight-for-length Z-score ≥ - 2. RESULTS: Infants fed F-100 and F-100D had higher weight gain than infants who received IF. Mean difference between F-100 and IF was 4.6 g/kg/d (95% CI 1.5-7.6, P = 0.004) and between F-100D and IF was 3.1 g/kg/d (95% CI 0.6-5.5, P = 0.015). Total energy intake from study diet and breast milk was significantly higher in infants fed F-100 compared with other two diets (P = 0.001 in each case). RSL was highest in infants fed F-100 but serum sodium showed no sign of elevation. Urinary specific gravity and serum sodium values were within normal range. CONCLUSIONS: F-100 can be safely used in the rehabilitation phase for infants u6m with SAM and there is no need to prepare alternative formulations.

New quinoline-2-one/pyrazole derivatives; design, synthesis, molecular docking, anti-apoptotic evaluation, and caspase-3 inhibition assay.

We report the synthesis of new quinoline-2-one/pyrazole hybrids and their antiapoptotic activity. This effect was studied in sight of decreasing tissue damage induced by I/R in colon of rats using N-acetylcysteine (NAC) as anti-apoptotic reference. Compounds 6a, 6c and 6f showed significant improvement for oxidative stress parameters MDA, SOD, GSH and NOx in comparison with model group and greater than the reference NAC (N-acetylcysteine), whereas compounds 6d and 6e exhibited weaker antioxidant activity when compared with the reference NAC. Moreover, compounds 6a, 6c and 6f showed significant decrease in inflammatory mediators TNFα and CRB greater than NAC when compared to the model group especially compound 6c whose found CRB conc 1.90 (mg/dL) in comparison to NAC of conc 2.13 mg/dL. Additionally, colonic histopathological investigation was performed to all targeted compounds that indicates H&E sections of compounds 6a and 6f revealed apparent normal colonic cells while compound 6e showed dilated blood vessels with more apoptotic cells if compared with NAC. Caspase-3 inhibition assay revealed that compounds 6a, 6b and 6d weaken caspase-3 expression to an extent higher than NAC (1.063, 0.430, 0.731 and 1.115, respectively). Docking studies with caspase-3 revealed that most of the tested compounds showed good binding with the enzyme especially for compound 6d make several interactions better than that of the reference NAC.

Members of the human gut microbiota involved in recovery from Vibrio cholerae infection.

Given the global burden of diarrhoeal diseases, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhoea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. Here we conduct a detailed time-series metagenomic study of faecal microbiota collected during the acute diarrhoeal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children. To define the underlying mechanisms, we introduce into gnotobiotic mice an artificial community composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children. One of the species, Ruminococcus obeum, exhibits consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obeum luxS (autoinducer-2 (AI-2) synthase) expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing-mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants discloses that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.

Role of Bacterial-Fungal Consortium for Enhancement in the Degradation of Industrial Dyes.

BACKGROUND: The presence of anthraquinone (Disperse blue 64) and azodyes (Acid yellow 17) in a waterbody are considered among the most dangerous pollutants. METHODS: In this study, two different isolated microbes, bacterium and fungus, were individually and as a co-culture applied for the degradation of Disperse Blue 64 (DB 64) and Acid Yellow 17 (AY 17) dyes. The isolates were genetically identified based upon 16S (for bacteria) and ITS/5.8S (for fungus) rRNA genes sequences as Pseudomoans aeruginosa and Aspergillus flavus, respectively. RESULTS: The fungal/bacterial consortium exhibited a higher percentage of dyes degradation than the individual strains, even at a high concentration of 300 mg/L. Azoreductase could be identified as the main catabolic enzyme and the consortium could induce azoreductase enzyme in the presence of both dyes. However, the specific substrate which achieved the highest azoreductase specific activity was Methyl red (MR) (3.5 U/mg protein). The tentatively proposed metabolites that were detected by HPLC/MS suggested that the reduction process catalyzed the degradation of dyes. The metabolites produced by the action consortium on two dyes were safe on Vicia faba and Triticum vulgaris germination and health of seedlings. Toxicity of the dyes and their degradation products on the plant was different according to the type and chemistry of these compounds as well as the type of irrigated seeds. CONCLUSION: We submit that the effective microbial degradation of DB64 and AY17 dyes will lead to safer metabolic products.