Fecal-adherent mucus is a non-invasive source of primary human MUC2 for structural and functional characterization in health and disease.

The O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces. We hypothesized human fecal MUC2 (HF-MUC2) was accessible for purification and downstream structural and functional characterization. We tested this via histologic and quantitative imaging on human fecal sections; extraction from feces for proteomic and O-glycomic characterization; and functional studies via growth and metabolic assays in vitro. Quantitative imaging of solid fecal sections showed a continuous mucus layer of varying thickness along human fecal sections with barrier functions intact. Lectin profiling showed HF-MUC2 bound several lectins but was weak to absent for Ulex europaeus 1 (α1,2 fucose-binding) and Sambucus nigra agglutinin (α2,6 sialic acid-binding), and did not have obvious b1/b2 barrier layers. HF-MUC2 separated by electrophoresis showed high molecular weight glycoprotein bands (∼1-2 MDa). Proteomics and Western analysis confirmed the enrichment of MUC2 and potential MUC2-associated proteins in HF-MUC2 extracts. MUC2 O-glycomics revealed diverse fucosylation, moderate sialylation, and little sulfation versus porcine colonic MUC2 and murine fecal Muc2. O-glycans were functional and supported the growth of Bacteroides thetaiotaomicron (B. theta) and short-chain fatty acid (SCFA) production in vitro. MUC2 could be similarly analyzed from inflammatory bowel disease stools, which displayed an altered glycomic profile and differential growth and SCFA production by B. theta versus healthy samples. These studies describe a new non-invasive platform for human MUC2 characterization in health and disease.

Case-control study on the association between the GATA2 gene and premature myocardial infarction in the Iranian population.

In recent decades, due to the high prevalence of coronary artery disease (CAD) and myocardial infarction (MI), numerous studies have attempted to elucidate genetic contributing factors in these complex disorders. A very interesting gene in this regard is GATA-binding protein 2 (GATA2), an important regulator of various gene expressions in vascular endothelial cells. Accordingly, the association of different GATA2 polymorphisms with CAD and MI has already been evaluated. Rs2713604 is a genetic marker whose association with CAD has not been reproduced in previous studies. Considering the importance of replicating the initial association, the present case-control study aimed to examine the association of this intronic variant with premature MI in a sample of the Iranian population. In this study, 193 participants from Jahrom Hospital (Jahrom, Iran) were consecutively recruited during a 1.5-year period, and, following blood sampling, genomic DNA was extracted. We then proceeded to genotype rs2713604 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and statistically analyzed the data. After adjustment for hyperlipidemia, hypertension, and type 2 diabetes mellitus, the results of the multivariate regression analysis showed no significant association between rs2713604 and premature MI. Interestingly, the risk allele (A-allele) of rs2713604 displayed a slightly higher frequency among controls compared to cases.

Inflammation, diet, and type 2 diabetes: a mini-review.

Inflammation is a common feature of type 2 diabetes (T2D). Inflammatory cytokines increase in patients with type 2 diabetes, metabolic syndrome, and heart disease. Various types of cells can produce inflammatory cytokines and then release them into the bloodstream, where their complex interactions with target tissues raise a tissue-specific immune response. This review focused on C-reactive protein (CRP), tumor necrosis factor (TNF)-α as an inflammatory cytokine, and adiponectin produced by adipose tissues. Despite the major role of cytokines in the development of T2D, further studies are required to investigate the possible effects of the macronutrient composition of diet on these cytokines.

ADAMTS7 and ZC3HC1 Share Genetic Predisposition to Coronary Artery Disease and Large Artery Ischemic Stroke.

Coronary artery disease (CAD) and ischemic stroke (IS) are commonly considered distinct disease phenotypes. However, there is some evidence in favor of a degree of overlap between genetic susceptibility to CAD and genetic risk factors for IS. In the present study, we aimed to examine the role of two single-nucleotide polymorphisms (SNPs), rs3825807 and rs11556924, located in the ADAMTS7 and ZC3HC1 genes, respectively, associated with CAD in published GWASs in European populations and their possible contribution to the development of coronary atherosclerosis and cerebral LA atherosclerosis in a case-control study of an the Iranian population. The sample size was 400, and the methodology for SNP genotyping was ARMS-PCR. Both SNPs showed strong associations with CAD in the analyses comparing significant CAD and myocardial infarction (MI) with controls. None of them, however, were associated with MI in patients with significant CAD. Our findings further support the role of the ADAMTS7 locus in promoting atherosclerosis in LAs of the brain. Regarding ZC3HC1 rs11556924, our study further supports the observed association of rs11556924 with LA IS coming from previous GWASs. In conclusion, the data showed that common variants in ADAMTS7 and ZC3HC1 genes contribute to an increased risk for both CAD and LA (atherosclerotic) IS.

Serum lysyl oxidase concentration increases in long-standing systemic sclerosis: Can lysyl oxidase change over time?

Objectives: This study aims to investigate the association of serum lysyl oxidase (LOX) levels with systemic sclerosis (SSc), to examine the relationship between LOX and disease onset, and to evaluate the probable effects of hyperlipidemia on the circulating levels of LOX among patients with SSc. Patients and methods: Between May 2017 and November 2018, a total of 39 patients with SSc (2 males, 37 females; mean age: 46.6±12.3 years; range, 18 to 65 years) and 35 healthy controls (4 males, 31 females; mean age: 43.1±14.1 years; range, 18 to 65 years) were included. Serum LOX concentration was measured using the enzyme-linked immunoassay in triplicate. Results: We found higher levels of serum LOX in patients with SSc compared to healthy controls. There was a significant relationship between serum LOX levels and disease onset. Patients with long-standing disease demonstrated increased levels of LOX in the blood compared to the recent-onset group. Hyperlipidemia did not have a significant effect on circulating levels of LOX. There was a significant negative correlation between LOX levels and modified Rodnan Skin Score in the subgroup of patients with skin involvement only and in patients without gastrointestinal involvement. Conclusion: Our study findings show an increased level of LOX protein level in the blood of patients diagnosed with SSc. Hyperlipidemia seems not to affect the concentrations of LOX in the peripheral blood of patients with SSc.

The effect of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells in allergic asthma.

INTRODUCTION: Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppressive effects in previous studies. In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. RESULTS: The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10⁻7M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. CONCLUSION: In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction.