Low Bifidobacterium Abundance in the Lower Gut Microbiota Is Associated With Helicobacter pylori-Related Gastric Ulcer and Gastric Cancer.

Helicobacter pylori infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most H. pylori-infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the H. pylori-associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to H. pylori infection and related gastric diseases. Here, we studied H. pylori infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents (N = 375) in southwestern India by standard H. pylori culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent H. pylori strains (vacAs1i1m1cagA+) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the H. pylori-infected vs. H. pylori-non-infected individuals. Bifidobacterium (belonging to the phylum Actinobacteria) and Bacteroides (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the H. pylori+ group than the H. pylori- group (p < 0.05). On the contrary, for the H. pylori+ group, genus Dialister (bacteria belonging to the phylum Firmicutes) and genus Prevotella (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the H. pylori- group (p < 0.05). Notably, those who carried H. pylori in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance (p < 0.05) of several Bifidobacterium species (e.g., B. adolescentis, B. longum) in the lower gut suggesting a protective role of Bifidobacterium. Our results show the link between lower gastrointestinal microbes and upper gastrointestinal diseases. Moreover, the results are important for developing effective probiotic and early prognosis of severe gastric diseases.

Adaptive laboratory evolution of Vibrio cholerae to doxycycline associated with spontaneous mutation.

Cholera, caused by the Gram-negative bacterium Vibrio cholerae, remains a serious threat in underdeveloped countries. Although rehydration therapy has been the mainstay of disease management, antibiotics are also being used as an adjunct treatment, resulting in an increase in the circulation of antimicrobial-resistant V. cholerae strains. In the present study, adaptive laboratory evolution, whole-genome sequencing and molecular docking studies were performed to identify putative mutations related to doxycycline resistance in V. cholerae isolates. The V57L mutation in the RpsJ protein was identified to be important in conferring doxycycline resistance. As revealed by molecular docking studies, the mutation was identified to alter the ribosome structure near the doxycycline binding site. Doxycycline stress also induced co-resistance to colistin, a last-resort antibiotic to treat extensively drug-resistant bacteria. This study illustrates for the first time a possible mechanism of doxycycline-selected resistance in V. cholerae as well as doxycycline-selected co-resistance, warranting strict restrictions on the indiscriminate use of antibiotics.

Molecular trail for the anticancer behavior of a novel copper carbohydrazone complex in BRCA1 mutated breast cancer.

Novel chelated metal complexes were synthesized from carbohydrazones to thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild-type and mutated breast cancer cells: MCF-7 (BRCA1+ /ER+ ), MDA-MB-231 (BRCA1+ /ERα- ), HCC-1937 (BRCA1- /ERα- ), HCC1937/wt BRCA1, MX1 (BRCA1- /ERα- ), and MDA-MB-436 (BRCA1- /ERα- ) were screened for anti-cancer activity. Cu2 (HL)(HSO4 ) · H2 O]SO4 · 6 H2 O (CS2) is the most potent anticancer agent among the copper carbohydrazone and thiocarbohydrazone complexes analyzed in this study. It can be suggested that the presence of sulphate, as pharmacologically active centre, can induce cytotoxicity more effectively when compared to chlorine, bromine, perchlorate, and methanol. This is the first report demonstrating that CS2 can bind to DNA by hindering BamH1 activity and could induce DNA double strand breaks as evidenced by γ-H2AX expression. In addition to this, CS2 could also act as a Topo II inhibitor at a much lower concentration than etoposide and induce apoptosis, making it a potent anticancer agent. In combination with Pb, a potent ROS inducer, CS2 could induce synergistic anti-cancer activity in HR/ BRCA1 defective breast cancer cells. This is the first study reporting the mechanism involved in the induction of apoptosis for a metal chelated copper carbohydrazone complex and its combination effects with Pb in HR defective, BRCA1 mutated breast cancer cells.

Developmental wave of Brn3b expression leading to RGC fate specification is synergistically maintained by miR-23a and miR-374.

Differential regulation of Brn3b is essential for the Retinal Ganglion Cell (RGC) development in the two phases of retinal histogenesis. This biphasic Brn3b regulation is required first, during early retinal histogenesis for RGC fate specification and secondly, during late histogenesis, where Brn3b is needed for RGC axon guidance and survival. Here, we have looked into how the regulation of Brn3b at these two stages happens. We identified two miRNAs, miR-23a and miR-374, as regulators of Brn3b expression, during the early stage of RGC development. Temporal expression pattern of miR-23a during E10-19, PN1-7, and adult retina revealed an inverse relation with Brn3b expression. Though miR-374 did not show such a pattern, its co-expression with miR-23a evidently inhibited Brn3b. We further substantiated these findings by ex vivo overexpression of these miRNAs in E14 mice retina and found that miR-23a and miR-374 together brings about a change in Brn3b expression pattern in ganglion cell layer (GCL) of the developing retina. From our results, it appears that the combined expression of these miRNAs could be regulating the timing of the wave of Brn3b expression required for early ganglion cell fate specification and later for its survival and maturation into RGCs. Taken together, here we provide convincing evidences for the existence of a co-ordinated mechanism by miRNAs to down regulate Brn3b that will ultimately regulate the development of RGCs from their precursors.

PKSIIIexplorer: TSVM approach for predicting Type III polyketide synthase proteins.

UNLABELLED: PKSIIIexplorer, a web server based on 'transductive Support Vector Machine' allows fast and reliable prediction of Type III polyketide synthase proteins. It provides a simple unique platform to identify the probability of a particular sequence, being a type III polyketide synthases or not with moderately high accuracy. We hope that our method could serve as a useful program for the type III polyketide researchers. The tool is available at "http://type3pks.in/tsvm/pks3". ABBREVIATIONS: PKS - Polyketide synthase, CHS - Chalcone synthase, SVM - Support vector machine, MCC - Matthews Correlation Coefficient.