Quinoline-thiosemicarbazone-1,2,3-triazole-acetamide derivatives as new potent α-glucosidase inhibitors.

In this work, a novel series of quinoline-thiosemicarbazone-1,2,3-triazole-aceamide derivatives 10a-n as new potent α-glucosidase inhibitors was designed, synthesized, and evaluated. All the synthesized derivatives 10a-n were more potent than acarbose (positive control). Representatively, (E)-2-(4-(((3-((2-Carbamothioylhydrazineylidene)methyl)quinolin-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-phenethylacetamide (10n), as the most potent entry, with IC = 48.

Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome.

The etiology and mechanism of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are poorly understood and no biomarkers have been established. Specifically, the relationship between the immunologic, metabolic, and gastrointestinal abnormalities associated with ME/CFS and their relevance to established symptoms of the condition remain unclear. Relying on data from two independent pairs of ME/CFS and control cohorts, one at rest and one undergoing an exercise challenge, we identify a state of suppressed acute-phase innate immune response to microbial translocation in conjunction with a compromised gut epithelium in ME/CFS.

A review of waste-to-hydrogen conversion technologies for solid oxide fuel cell (SOFC) applications: Aspect of gasification process and catalyst development.

In the twenty-first century, there has been an increase in energy demand and waste production, due to the rising population of the world. One good approach for satisfying the energy demand and overcoming the waste management issues is to convert waste to energy. Additionally, using waste biomass as the feedstock of waste-to-energy (WtE) conversion methods makes them renewable and green and also helps the environmental challenges and reduces the emission of greenhouse gases (GHGs).

Associations Between Subclass Profile of IgG Response to Gluten and the Gastrointestinal and Motor Symptoms in Children With Cerebral Palsy.

Objective: Gastrointestinal problems are often seen in children with cerebral palsy, although the etiology and underlying mechanisms are not fully understood. Recent data point to significantly elevated levels of IgG antibody to dietary gluten in cerebral palsy independent of celiac disease, a gluten-mediated autoimmune enteropathy. We aimed to further characterize this antibody response by examining its subclass distribution and target reactivity in the context of relevant patient symptom profile.

Celiac disease serology and gut microbiome following proton pump inhibitor treatment.

Background: Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors.

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG.

Background & Aims: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms.

Methods: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016.

Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis.

Background & Aims: There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD.

Methods: We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type.

Reducing the Immunogenic Potential of Wheat Flour: Silencing of Alpha Gliadin Genes in a U.S. Wheat Cultivar.

The alpha gliadins are a group of more than 20 proteins with very similar sequences that comprise about 15%-20% of the total flour protein and contribute to the functional properties of wheat flour dough. Some alpha gliadins also contain immunodominant epitopes that trigger celiac disease, a chronic autoimmune disease that affects approximately 1% of the worldwide population. In an attempt to reduce the immunogenic potential of wheat flour from the U.

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential.

The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44 CD127 cytotoxic ILC1s and NKp44 CD127 helper ILC1s, while ILC3s only represent a minor population.

Elimination of Omega-1,2 Gliadins From Bread Wheat () Flour: Effects on Immunogenic Potential and End-Use Quality.

The omega-1,2 gliadins are a group of wheat gluten proteins that contain immunodominant epitopes for celiac disease (CD) and also have been associated with food allergies. To reduce the levels of these proteins in the flour, bread wheat ( cv. Butte 86) was genetically transformed with an RNA interference plasmid that targeted a 141 bp region at the 5' end of an omega-1,2 gliadin gene.

Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2.

Microbe-host interactions are generally homeostatic, but when dysfunctional, they can incite food sensitivities and chronic diseases. Celiac disease (CeD) is a food sensitivity characterized by a breakdown of oral tolerance to gluten proteins in genetically predisposed individuals, although the underlying mechanisms are incompletely understood. Here we show that duodenal biopsies from patients with active CeD have increased proteolytic activity against gluten substrates that correlates with increased Proteobacteria abundance, including Pseudomonas.

Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins.

Background & Aims: Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial.

Methods: C57BL/6 (control), Myd88, Ticam1, and Il15 mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week.

Nonceliac Wheat Sensitivity: An Immune-Mediated Condition with Systemic Manifestations.

Non-celiac wheat sensitivity (NCWS) is characterized by gastrointestinal and extra-intestinal symptoms following the ingestion of gluten-containing cereals in subjects without celiac disease or wheat allergy. The identity of the molecular triggers in these cereals responsible for the symptoms of NCWS remains to be delineated. Recent research has identified a biological basis for the condition, with the observation of systemic immune activation in response to microbial translocation that appears to be linked to intestinal barrier defects.

Inflammatory biomarkers in psychosis and clinical high risk populations.

Background: Immunological, nutritional, and microbial factors have been implicated in the pathophysiology of schizophrenia, but the interrelationship among measures is understudied. In particular, an increase in the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) is associated with all phases of the illness, and may be associated with other inflammatory markers. Vitamin D is a modulator of the immune system, and LPS antibodies are an indirect measure of gut barrier function.

Hispanic Spinocerebellar Ataxia Type 35 (SCA35) with a Novel Frameshift Mutation.

Genetic mutations in transglutaminase 6 (TGM6) are recently identified to be associated with spinocerebellar ataxia type 35 (SCA35). We report a Hispanic SCA35 patient, who was confirmed to have a heterozygous, single-nucleotide deletion in TGM6, causing a frameshift mutation with a premature stop codon. An immune-mediated ataxia previously found to be associated with autoantibody reactivity to TG6 may share a similar pathomechanism to SCA35, suggesting a converging role for TG6 in cerebellar function.

Autoantibodies in the Extraintestinal Manifestations of Celiac Disease.

Increased antibody reactivity towards self-antigens is often indicative of a disruption of homeostatic immune pathways in the body. In celiac disease, an autoimmune enteropathy triggered by the ingestion of gluten from wheat and related cereals in genetically predisposed individuals, autoantibody reactivity to transglutaminase 2 is reflective of the pathogenic role of the enzyme in driving the associated inflammatory immune response. Autoantibody reactivity to transglutaminase 2 closely corresponds with the gluten intake and clinical presentation in affected patients, serving as a highly useful biomarker in the diagnosis of celiac disease.

Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis.

Background: Gluten sensitivity refers to prominent immunological responses to gluten, usually in conjunction with elevated levels of serum antigliadin antibody (AGA). The association between AGA and cerebellar ataxias has been inconsistently reported.

Methods: We performed a systematic literature search and a meta-analysis to study the weighted pooled OR of idiopathic cerebellar ataxia (IDCA) cases to controls or to hereditary ataxia (HA) for AGA seropositivity using fixed effect model.