Invasive Salmonella Typhimurium Colonizes Gallbladder and Contributes to Gallbladder Carcinogenesis through Activation of Host Epigenetic Modulator KDM6B.

Gallbladder stones alone do not explain the risk of gallbladder cancer (GBC) as the sole etiological factor. Chronic microbial infection, particularly Salmonella, has been implicated in GB carcinogenesis, but its causative role and the underlying mechanisms are largely unknown. We studied gut and gallbladder tissue microbiome through targeted metagenomics to identify pathogenic bacteria in GBC.

Rab7-dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis.

Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system.

SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function.

One of the mechanisms shaping the pathophysiology during the infection of enteric pathogen Salmonella Typhimurium is host PTM machinery utilization by the pathogen encoded effectors. Salmonella Typhimurium (S. Tm) during infection in host cells thrives in a vacuolated compartment, Salmonella containing vacuole (SCV), which sequentially acquires host endosomal and lysosomal markers.

Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature.

Fecal microbiota transplantation refurbishes the crypt-associated microbiota in ulcerative colitis.

A crypt autochthonous microbial population called crypt-associated microbiota (CAM) is localized intimately with gut regenerative and immune machinery. The present report utilizes laser capture microdissection coupled with 16S amplicon sequencing to characterize the CAM in patients with ulcerative colitis (UC) before and after fecal microbiota transplantation with anti-inflammatory diet (FMT-AID). Compositional differences in CAM and its interactions with mucosa-associated microbiota (MAM) were compared between the non-IBD controls and in patients with UC pre- and post-FMT (n = 26).

Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer.

The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls: p',p' dichloro diphenyl trichloroethane (DDT), p'p' dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA).

Gemini lipid nanoparticle (GLNP)-mediated oral delivery of TNF-α siRNA mitigates gut inflammation inhibiting the differentiation of CD4 T cells.

Proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) are critical mediators of inflammatory bowel disease pathogenesis, and are important targets to restore intestinal homeostasis. Herein, we present the engineering and screening of gemini lipid nanoparticles (GLNPs) for siRNA delivery to colon epithelial cells, macrophages and dendritic cells, and their ability to deliver siRNA therapeutics to the inflamed gastrointestinal tract. We synthesized eight gemini cationic lipids by tethering two lithocholic acid molecules through 3'-hydroxyl- and 24'-carboxyl-derived ammonium groups using different polyalkylene spacers.

Bidirectional regulation between AP-1 and SUMOylation pathway genes modulates inflammatory signaling during Salmonella infection.

Post-translational modifications (PTMs), such as SUMOylation, are known to modulate fundamental processes of a cell. Infectious agents such as Salmonella Typhimurium (STm), which causes gastroenteritis, utilize the PTM mechanism SUMOylation to hijack the host cell. STm suppresses host SUMO pathway genes UBC9 (also known as UBE2I) and PIAS1 to perturb SUMOylation for an efficient infection.

Activation of epigenetic regulator KDM6B by Typhimurium enables chronic infections.

Non-typhoidal (NTS) infections result in self limiting gastroenteritis except in rare cases wherein manifestations of chronic infections can occur. Strategies employed by to thrive in hostile environments of host during chronic infections are complex and multifaceted. In chronic state, a coordinated action of bacterial effectors allows reprogramming of macrophages to M2 subtype and thereby creating a permissible replicative niche.

Molecular determinants of peaceful coexistence versus invasiveness of non-Typhoidal Salmonella: Implications in long-term side-effects.

The genus Salmonella represents a wide range of strains including Typhoidal and Non-Typhoidal Salmonella (NTS) isolates that exhibit illnesses of varied pathophysiologies. The more frequent NTS ensues a self-limiting enterocolitis with rare occasions of bacteremia or systemic infections. These self-limiting Salmonella strains are capable of subverting and dampening the host immune system to achieve a more prolonged survival inside the host system thus leading to chronic manifestations.

Cell culture techniques in gastrointestinal research: Methods, possibilities and challenges.

Cell culture is one of the most valuable tools which is being applied in both fundamental and applied gastrointestinal research. The cells are isolated from their natural location (in vivo) and further propagated in vitro or artificial environment and studied. Over the years, several methods have been devised to isolate animal cells derived from the gut and culture them in vitro to study the functions and biology in the context of complex gastrointestinal diseases.

Nanoparticle-mediated gene therapy strategies for mitigating inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an autoimmune disorder of the gastrointestinal tract (GIT) where Ulcerative Colitis (UC) displays localized inflammation in the colon, and Crohn's Disease (CD) affects the entire GIT. Failure of current therapies and associated side-effects bring forth serious social, economic, and health challenges. The gut epithelium provides the best target for gene therapy delivery vehicles to combat IBD.

A regulatory circuit between lncRNA and TOR directs amino acid uptake in yeast.

Long non coding RNAs (lncRNAs) have emerged as crucial players of several central cellular processes across eukaryotes. Target of Rapamycin (TOR) is a central regulator of myriad of fundamental cellular processes including amino acid transport under diverse environmental conditions. Here we investigated the role of lncRNA in TOR regulated amino acid uptake in S.

Pouch of Douglas internal hernia successfully treated laparoscopically.

A rare case of internal herniation of a peritoneal defect in the pouch of Douglas is being reported. It presented as a case of intestinal obstruction, which after investigation, on laparoscopic exploration was found to be a case of internal hernia getting obstructed in the pouch of Douglas. It was successfully treated by marsupialisation of the defect laparoscopically.

A nanogel based oral gene delivery system targeting SUMOylation machinery to combat gut inflammation.

Poor success rates and challenges associated with the current therapeutic strategies of inflammatory bowel disease (IBD) have accelerated the emergence of gene therapy as an alternative treatment option with great promise. However, oral delivery of nucleic acids (NAs) to an inflamed colon is challenged by multiple barriers presented by the gastrointestinal, extracellular and intracellular compartments. Therefore, we screened a series of polyaspartic acid-derived amphiphilic cationic polymers with varied hydrophobicity for their ability to deliver NAs into mammalian cells.

Oral Delivery of Cholic Acid-Derived Amphiphile Helps in Combating Salmonella-Mediated Gut Infection and Inflammation.

A major impediment to developing effective antimicrobials against Gram-negative bacteria like Salmonella is the ability of the bacteria to develop resistance against existing antibiotics and the inability of the antimicrobials to clear the intracellular bacteria residing in the gastrointestinal tract. As the critical balance of charge and hydrophobicity is required for effective membrane-targeting antimicrobials without causing any toxicity to mammalian cells, herein we report the synthesis and antibacterial properties of cholic acid-derived amphiphiles conjugated with alkyl chains of varied hydrophobicity. Relative to other hydrophobic counterparts, a compound with hexyl chain (6) acted as an effective antimicrobial against different Gram-negative bacteria.

A SUMOylation-dependent switch of RAB7 governs intracellular life and pathogenesis of Typhimurium.

Typhimurium is an intracellular pathogen that causes gastroenteritis in humans. Aided by a battery of effector proteins, Typhimurium resides intracellularly in a specialized vesicle, called the -containing vacuole (SCV) that utilizes the host endocytic vesicular transport pathway (VTP). Here, we probed the possible role of SUMOylation, a post-translation modification pathway, in SCV biology.

Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy.

Colorectal cancer (CRC) is one of the most prevalent cancers diagnosed worldwide. Despite recent advances, resistance to cytotoxic and targeted therapy remains one of the greatest challenges in long-term management of colorectal cancer therapy. Recently established role of mTOR signaling in proliferation of CRC has incited for evaluation of mTOR kinase specific inhibitors in CRC therapy.

Chitosan coated PluronicF127 micelles for effective delivery of Amphotericin B in experimental visceral leishmaniasis.

The goal of study was to develop micellar formulation of Amphotericin B (AmB) to improve its antileishmanial efficacy. AmB loaded pluronic F127 (PF 127) micelles were developed and coated with chitosan (Cs-PF-AmB-M) to accord immunoadjuvant and macrophage targeting properties. Hemolysis and cytotoxicity studies demonstrated that Cs-PF-AmB-M was 7.

Sumoylation as an Integral Mechanism in Bacterial Infection and Disease Progression.

Post translational modification pathways regulate fundamental processes of cells and thus govern vital functions. Among these, particularly the modification with Small Ubiquitin-like Modifiers (SUMO) is being recognized as a pathway crucial for cell homeostasis and health. Understandably, bacterial pathogens intervene with the SUMO pathway of the host for ensuring successful infection.

Vapor Phase Hydrogenation of Nitrobenzene to Aniline Over Carbon Supported Ruthenium Catalysts.

A series of Ru/Carbon catalysts (0.5-6.0 wt%) were prepared by impregnation method.

Understanding the complexities of Salmonella-host crosstalk as revealed by in vivo model organisms.

Foodborne infections caused by non-typhoidal Salmonellae, such as Salmonella enterica serovar Typhimurium (ST), pose a major challenge in the developed and developing world. With constant rise of drug-resistant strains, understanding the epidemiology, microbiology, pathogenesis and host-pathogen interactions biology is a mandatory requirement to enable health systems to be ready to combat these illnesses. Patient data from hospitals, at least from some parts of the world, have aided in epidemiological understanding of ST-mediated disease.