Dexamethasone Upregulates the Expression of the Human SLC26A3 (DRA, Down-Regulated in Adenoma) Transporter (an IBD Susceptibility Gene) in Intestinal Epithelial Cells and Attenuates Gut Inflammation.

Background: Down-Regulated in Adenoma (DRA) plays a critical role in intestinal chloride absorption and a decrease in its expression is a key event in diarrheal disorders. Recently, DRA has emerged as an Inflammatory Bowel Disease (IBD) susceptibility gene. Therefore, the strategies to upregulate DRA expression are potentially novel approaches to not only treat IBD-associated diarrhea but also gut inflammation.

Impact of soluble epoxide hydrolase inhibition on silica-induced pulmonary fibrosis, ectopic lymphoid neogenesis, and autoantibody production in lupus-prone mice.

Objective: Acute intranasal (IN) instillation of lupus-prone NZBWF1 mice with crystalline silica (cSiO) triggers robust lung inflammation that drives autoimmunity. Prior studies in other preclinical models show that soluble epoxide hydrolase (sEH) inhibition upregulates pro-resolving lipid metabolites that are protective against pulmonary inflammation. Herein, we assessed in NZBWF1 mice how acute IN cSiO exposure with or without the selective sEH inhibitor TPPU influences lipidomic, transcriptomic, proteomic, and histopathological biomarkers of inflammation, fibrosis, and autoimmunity.

Nasal and Serum Immunoglobulin E Levels in Symptomatic Allergic Rhinitis Patients: A Case-Control Study.

Allergic Rhinitis (AR) is an inflammatory condition of the nasal mucosa triggered by Immunoglobulin E (IgE) mediated response to exposure to allergens. The most common symptoms are nasal obstruction, sneezing, runny nose and these in addition to swollen, itchy, red and watery eyes. Recent studies have shown highly elevated immunoglobulin E levels in the airway mucosa independently of serum IgE levels and atopic status.

Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model.

To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR.

A Novel Role of SLC26A3 in the Maintenance of Intestinal Epithelial Barrier Integrity.

Background & Aims: The down-regulated in adenoma (DRA) protein, encoded by SLC26A3, a key intestinal chloride anion exchanger, has recently been identified as a novel susceptibility gene for inflammatory bowel disease (IBD). However, the mechanisms underlying the increased susceptibility to inflammation induced by the loss of DRA remain elusive. Compromised barrier is a key event in IBD pathogenesis.

Hepatocyte nuclear factor-4α regulates expression of the serotonin transporter in intestinal epithelial cells.

The serotonin transporter (SERT) functions to regulate the availability of serotonin (5-HT) in the brain and intestine. An intestine-specific mRNA variant arising from a unique transcription start site and alternative promoter in the SERT gene has been identified (iSERT; spanning exon 1C). A decrease in SERT is implicated in several gut disorders, including inflammatory bowel diseases (IBD).

Serotonin transporter untranslated regions influence mRNA abundance and protein expression.

The serotonin transporter (SERT, SLC6A4) is a Na-dependent transporter that regulates the availability of serotonin (5-HT, 5-hydroxytryptamine), a key neurotransmitter and hormone in the brain and the intestine. The human SERT gene consists of two alternate promoters that drive expression of an identical SERT protein. However, there are different mRNA transcript variants derived from these two promoters that differ in their 5' untranslated region (5'UTR), which is the region of the mRNA upstream from the protein-coding region.

Serotonin Modulates AhR Activation by Interfering with CYP1A1-Mediated Clearance of AhR Ligands.

Background/aims: Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter and hormone with important physiological functions in many organs, including the intestine. We have previously shown that 5-HT activates the aryl hydrocarbon receptor (AhR) in intestinal epithelial cells (IECs) via a serotonin transporter (SERT)-dependent mechanism. AhR is a nuclear receptor that binds a variety of molecules including tryptophan (TRP) metabolites to regulate physiological processes in the intestine including xenobiotic detoxification and immune modulation.

Effect of Short-Term Placebo-Controlled Consumption of Probiotic Yoghurt and Indian Curd on the Streptococcus mutans Level in Children Undergoing Fixed Interceptive Orthodontic Therapy.

Objective: To examine the effect of short-term consumption of probiotic yoghurt, Indian curd, and ultra-heated yoghurt as placebo on the levels of salivary and plaque in children undergoing fixed interceptive orthodontic therapy.

Methods: A placebo-controlled double-blind study was carried out in a total of 30 children (8-15 years). The level in the plaque and saliva were taken at the baseline and 2 weeks after the initiation of fixed orthodontic treatment by Dentocult SM kits.

TM4SF18 is aberrantly expressed in pancreatic cancer and regulates cell growth.

Current therapies for pancreatic ductal adenocarcinoma (PDAC) only modestly impact survival and can be highly toxic. A greater understanding of the molecules regulating this disease is critical for identifying new drug targets and developing more effective therapies. The L6 family of proteins are known to be positive regulators of tumor growth and metastasis among various cancers.

Serotonin Transporter Deficiency is Associated with Dysbiosis and Changes in Metabolic Function of the Mouse Intestinal Microbiome.

Serotonin transporter (SERT) plays a critical role in regulating extracellular availability of serotonin (5-HT) in the gut and brain. Mice with deletion of SERT develop metabolic syndrome as they age. Changes in the gut microbiota are being increasingly implicated in Metabolic Syndrome and Diabetes.

Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR.

Aryl hydrocarbon receptor (AhR) is a nuclear receptor that controls xenobiotic detoxification via induction of cytochrome P450 1A1 (CYP1A1) and regulates immune responses in the intestine. Metabolites of L-tryptophan activate AhR, which confers protection against intestinal inflammation. We tested the hypothesis that serotonin (5-HT) is an endogenous activator of AhR in intestinal epithelial cells.

Infection with enteric pathogens Salmonella typhimurium and Citrobacter rodentium modulate TGF-beta/Smad signaling pathways in the intestine.

Salmonella and Citrobacter are gram negative, members of Enterobacteriaceae family that are important causative agents of diarrhea and intestinal inflammation. TGF-β1 is a pleiotropic multifunctional cytokine that has been implicated in modulating the severity of microbial infections. How these pathogens alter the TGF-β1 signaling pathways in the intestine is largely unknown.

Comparative genetic variability in HIV-1 subtype C nef gene in early age groups of infants.

Targeting properties of vertically transmitted viruses in early infancy is important to understand disease progression. To investigate genotypic characteristics of transmitted viruses, blood samples were obtained from infants aged 6 weeks-18 months, categorized in two age groups, acute (<6 months) and early (>6-18 months). Nef having an important role in pathogenesis was selected to explore the viral characteristics.

Role of SHP2 protein tyrosine phosphatase in SERT inhibition by enteropathogenic (EPEC).

Enteropathogenic (EPEC), one of the diarrheagenic pathotypes, is among the most important food-borne pathogens infecting children worldwide. Inhibition of serotonin transporter (SERT), which regulates extracellular availability of serotonin (5-HT), has been implicated previously in EPEC-associated diarrhea. EPEC was shown to inhibit SERT via activation of protein tyrosine phosphatase (PTPase), albeit the specific PTPase involved is not known.

Estradiol Level on Day 2 and Day of Trigger: A Potential Predictor of the IVF-ET Success.

Objective: To evaluate role of serum estradiol levels in predicting likelihood of pregnancy in women undergoing GnRH-a protocol in IVF-ET cycles.

Design: A 3-year retrospective analysis of estradiol levels on down-regulated day 2, day 6, and day of hCG trigger and subsequent clinical pregnancy rates.

Setting: A university hospital tertiary referral centre.

Targeted detection of 65 kDa heat shock protein gene in endometrial biopsies for reliable diagnosis of genital tuberculosis.

Objective: To evaluate the clinical utility of PCR compared with other available diagnostic modalities in prompt diagnosis of female genital tuberculosis causing infertility.

Study Design: Prospective case-controlled trial. Premenstrual endometrial biopsy specimens were collected from 150 infertile women of reproductive age group suspected of having genital tuberculosis.