Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn's Disease.

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting subspecies (MAP), long considered a putative cause, would favorably affect Crohn's disease. A double-blind multicenter study of adults with active Crohn's disease, (i.e.

neutralization of IL-6 receptor exacerbates damage to intestinal epithelial cells during infection.

Like TNFα, IL-6 is upregulated in Crohn's disease (CD) especially in patients associated with (MAP) infection, and both cytokines have been targeted as a therapeutic option for the treatment of the disease despite the accepted partial response in some patients. Limited response to anti-IL-6 receptor-neutralizing antibodies therapy may be related to the homeostatic dual role of IL-6. In this study, we investigated the effects and the signaling mechanism of IL-6 involved in intestinal epithelial integrity and function during MAP infection using an model that consists of THP-1, HT-29 and Caco-2 cell lines.

An In Vivo Model of Propionic Acid-Rich Diet-Induced Gliosis and Neuro-Inflammation in Mice (FVB/N-Tg(GFAPGFP)14Mes/J): A Potential Link to Autism Spectrum Disorder.

Evidence shows that Autism Spectrum Disorder (ASD) stems from an interplay of genetic and environmental factors, which may include propionic acid (PPA), a microbial byproduct and food preservative. We previously reported that in vitro treatment of neural stem cells with PPA leads to gliosis and neuroinflammation. In this study, mice were exposed ad libitum to a PPA-rich diet for four weeks before mating.

Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis.

Background: Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. encodes a member of the cytochrome P450 superfamily of enzymes.

Cytokine expression in subjects with ssp. positive blood cultures and a meta-analysis of cytokine expression in Crohn's disease.

Objectives: 1) Culture ssp. (MAP)from blood, 2) assess infection persistence, 3) determine Crohn's disease (CD) cytokine expression, 4) compare CD cytokine expression to tuberculosis, and 5) perform a meta-analysis of cytokine expression in CD.

Methods: The Temple University/Abilene Christian University (TU/ACU) study had a prospective case control design with 201 subjects including 61 CD patients and 140 non-CD controls.

Fisetin modulates the gut microbiota alongside biomarkers of senescence and inflammation in a DSS-induced murine model of colitis.

Colitis, a subtype of inflammatory bowel disease (IBD), is a multifactorial disorder characterized by chronic inflammation of the colon. Among various experimental models used in the study of IBD, the chemical colitogenic dextran sulfate sodium (DSS) is most commonly employed to induce colitis in vivo. In the search for new therapeutic strategies, Fisetin, a flavonoid found in many fruits and vegetables, has recently garnered attention for its senolytic properties.

The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interactions, restrictive and repetitive behavior, and a wide range of cognitive impediments. The prevalence of ASD tripled in the last 20 years and now affects 1 in 44 children. Although ASD's etiology is not yet elucidated, a growing body of evidence shows that it stems from a complex interplay of genetic and environmental factors.

Study of hesperetin effect on modulating transcription levels of MLH1 and MSH2 genes in SKBR3 breast cancer cell line.

Hesperetin (HSP), a flavonoid, has been validated to modify gene expression and function as an epigenetic agent to stop the development of breast carcinoma cells. HSP was investigated in this research to evaluate the expression of the MLH1 and MSH2 genes in cancerous breast cell lines (SKBR3) and healthy cell lines (MCF-11A) after exposure to different dosages (200, 400, and 600 µM/mL) of HSP. After 48 h of exposure, SKBR3's half-maximal inhibitory concentration was 289.

The dual role of interleukin-6 in Crohn's disease pathophysiology.

Interleukin-6 (IL-6) is a key mediator cytokine of the immune response as well as a regulator of many physiological and pathological processes. In Crohn's disease (CD), cytokine imbalance rules the intestinal microenvironment and leads to chronic inflammation of the gut. Pro-inflammatory cytokines are generally upregulated in inflammatory bowel disease (IBD) including TNFα and IL-6.

Unveiling the antibacterial and antioxidant potential of leaf extracts: recent findings.

L., a member of the Araliaceae family, is a commonly known decorative plant with recognized medicinal activities. In this study, the ethanolic extract from leaves was investigated for its total polyphenolic and flavonoid contents, as well as its antioxidant and antibacterial properties.

Folate and Vitamin B Deficiency Exacerbate Inflammation during (MAP) Infection.

Folate and vitamin B deficiency is highly prevalent among Crohn's disease (CD) patients. Furthermore, CD pathology can be mediated by subsp. (MAP) infection.

Attenuation of Excess TNF-α Release in Crohn's Disease by Silencing of iRHOMs 1/2 and the Restoration of TGF-β Mediated Immunosuppression Through Modulation of TACE Trafficking.

TNFα converting enzyme (TACE) is a transmembrane metalloprotease that sheds an assortment of signaling receptors, cytokines, growth factors, and pro-inflammatory mediators. In Crohn's disease (CD), TACE activity is upregulated, resulting in a marked increase of TNFα secretion and inflammation. Although treatment of CD with TNFα monoclonal antibodies is beneficial, many patients are at risk for acquiring opportunistic infections, and the treatment efficacy of TNFα monoclonal antibodies typically decreases over time.

Plasma miRNA Profile of Crohn's Disease and Rheumatoid Arthritis Patients.

Crohn's disease (CD) and rheumatoid arthritis (RA) are immune mediated inflammatory diseases. Several studies indicate a role for microRNAs (miRNAs) in the pathogenesis of a variety of autoimmune diseases, including CD and RA. Our study's goal was to investigate circulating miRNAs in CD and RA patients to identify potential new biomarkers for early detection and personalized therapeutic approaches for autoimmune diseases.

Cathelicidin Mediates an Anti-Inflammatory Role of Active Vitamin D (Calcitriol) During Infection.

Vitamin D is a key regulator in calcium and phosphorus metabolism which are essential for maintaining bone health. Recent reports also showed a role for vitamin D in immune regulation which may be linked to vitamin D deficiency in autoimmune disorders including inflammatory diseases and Crohn's disease (CD). This study examines the role of vitamin D deficiency in the regulation of Cathelicidin Antimicrobial Peptide () in CD-like macrophages.

Extra-Pulmonary Complications in SARS-CoV-2 Infection: A Comprehensive Multi Organ-System Review.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is typically presented with acute symptoms affecting upper and lower respiratory systems. As the current pandemic progresses, COVID-19 patients are experiencing a series of nonspecific or atypical extra-pulmonary complications such as systemic inflammation, hypercoagulability state, and dysregulation of the renin-angiotensin-aldosterone system (RAAS). These manifestations often delay testing, diagnosis, and the urge to seek effective treatment.

The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation.

Vitamin deficiency is well known to contribute to disease development in both humans and other animals. Nonetheless, truly understanding the role of vitamins in human biology requires more than identifying their deficiencies. Discerning the mechanisms by which vitamins participate in health is necessary to assess risk factors, diagnostics, and treatment options for deficiency in a clinical setting.

Enteropathogenic infections modulate intestinal serotonin transporter (SERT) function by activating Toll-like receptor 2 (TLR-2) in Crohn's disease.

Serotonin (5-hydroxytryptamine [5-HT]) is an intestinal neuromodulator that regulates several essential enteric physiological functions such as absorption or secretion of fluids, and peristaltic reflexes. Availability of the intestinal 5-HT is dependent on serotonin transporter (SERT), which uptakes 5-HT and facilitates its degradation. Interestingly, Toll-like receptor 2 (TLR-2) is co-localized with 5-HT, which suggests a possible impact of neuroendocrine cells in the inflammatory response through TLR-2 activation.

Modulation of Function by Spermidine in CRISPR-Cas9-Edited T-Cells Associated with Crohn's Disease and Rheumatoid Arthritis.

Crohn's Disease (CD) and Rheumatoid Arthritis (RA) share some single nucleotide polymorphisms (SNPs) in protein tyrosine phosphatase non-receptor types 2 and 22 (). Recently, we reported that clinical samples from CD and RA patients associated with or genotypes were linked to overactive immune response and exacerbation of inflammation. Here, we investigated in vitro the effects of these SNPs in Jurkat T-cells using CRISPR-Cas9.

Coronavirus Disease 2019 (COVID-19) Diagnostic Tools: A Focus on Detection Technologies and Limitations.

The ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a severe threat to human health and the global economy and has resulted in overwhelming stress on health care systems worldwide. Despite the global health catastrophe, especially in the number of infections and fatalities, the COVID-19 pandemic has also revolutionized research and discovery with remarkable success in diagnostics, treatments, and vaccine development. The use of many diagnostic methods has helped establish public health guidelines to mitigate the spread of COVID-19.

Nicotine Increases Macrophage Survival through α7nAChR/NF-κB Pathway in Infection.

Recently, we reported that nicotine plays a role in the failure of the macrophage in the clearance of subspecies (MAP) during infection in Crohn's disease smokers. We also demonstrated that nicotine enhances macrophages cellular survival during MAP infection. Blocking α7 nicotinic acetylcholine receptor (α7nAChR) with the pharmacological antagonist-mecamylamine-subverted the anti-inflammatory effect of nicotine in macrophages.

Anti-TNF-α agents Modulate SARS-CoV-2 Receptors and Increase the Risk of Infection Through Notch-1 Signaling.

Although millions of patients with underlining conditions are treated primarily with anti-TNF-α agents, little is known about the safety of this standard therapy during the coronavirus disease-2019 (COVID-19) pandemic. In this study, we investigated the effect of anti-TNF-α monoclonal antibodies on the cellular entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increasing the risk of COVID-19 development. We focused on the expression of angiotensin-converting enzyme II (ACE2), type II transmembrane serine proteases (TMPRSS2)/TNF-α converting enzyme (TACE) ratio.

Presence of Infection by subsp. in the Blood of Patients with Crohn's Disease and Control Subjects Shown by Multiple Laboratory Culture and Antibody Methods.

subspecies (MAP) has long been suspected to be involved in the etiology of Crohn's disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to test new rapid culture methods for MAP in human subjects and to assess the degree of viable culturable MAP bacteremia in CD patients compared to controls.

Anti-MAP Triple Therapy Supports Immunomodulatory Therapeutic Response in Crohn's Disease through Downregulation of NF-κB Activation in the Absence of MAP Detection.

We previously reported that the triple antibiotic formulation, known as anti-MAP therapy, exhibits unique synergistic antimicrobial activity and should be effective for treatment of Crohn's disease (CD) associated with subspecies (MAP). The absence of MAP detection in some CD cases may be linked to poor diagnostics or lack of association with the disease. To understand the therapeutic response of some CD patients to anti-MAP therapy in absence of MAP detection, we investigated the immunomodulatory potency of anti-MAP therapy and its major ingredients, clarithromycin (CLA) and rifabutin (RIF), in THP-1, Caco-2, and Jurkat T-cells.

Nicotine Modulates MyD88-Dependent Signaling Pathway in Macrophages during Mycobacterial Infection.

Recently, we reported that cigarette smoking, and especially nicotine, increases susceptibility to mycobacterial infection and exacerbates inflammation in patients with Crohn's disease (CD). The macrophagic response to subspecies (MAP) in CD and (MTB) continues to be under investigation. The role of toll-like-receptors (TLRs) and cytoplasmic adaptor protein (MyD88) in proinflammatory response during Mycobacterial infection has been suggested.

MiR-146a polymorphism modulates Notch-1/IL-6 signaling during infection: a possible risk factor for Crohn's disease.

Background: MiR-146a, an effector mediator, targets Notch-1 and regulates the innate and adaptive immune systems response. Recently, we reported that Notch-1 signaling plays a key role in macrophage polarization and response during infection. We employed (MAP) infection in Crohn's disease (CD) as a model to demonstrate the role of Notch-1/IL-6 signaling on MCL-1 based apoptosis and intracellular MAP infection and persistence.