Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease

Chang, Hsueh-Lu; Chen, Guei-Rung; Hsiao, Po-Jen; Chiu, Chih-Chien; Tai, Ming‐Cheng; Kao, Chung-Cheng; Tsai, Dung-Jang; Su, Hao; Chen, Yu-Hsuan; Chen, Wei-Teing; Su, Sui-Lung

doi:10.1097/md.0000000000021045

Cited by 5 publications

(4 citation statements)

References 106 publications

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“…32 On the other hand, IL-6 can induce STAT3 phosphorylation in colon cancer cells with overexpressed RAB3C, which promotes the migration of colon cancer cells. 33 More importantly, ZC3H12B binds to the IL-6 mRNA, decreasing the production of IL-6 protein upon stimulation with IL-1b, which is in accordance with our findings. 21 Even more so, a prior study found that miR-155-5p amplified the expression of IL-6 in thyroid follicle cells and also increased the IL-6 expression in hyperlipidemia and patients with familial hypercholesterolemia.…”

Section: Discussionsupporting

confidence: 91%

M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B

Ling

et al. 2021

Molecular Therapy - Oncolytics

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Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set out to explore the possible role of M2 macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophagederived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3¿ UTR, as identified by dual luciferase reporter gene. Meanwhile, gain-and lossof function experimentation on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3 + T cell proliferation and the proportion of interferon (IFN)-g + T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.

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Section: Discussionsupporting

confidence: 91%

M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B

Ling

et al. 2021

Molecular Therapy - Oncolytics

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“…Patients in this group received GCs, and effectiveness of GCs was shown to be increased when alternative rs1801133 allele was present in children with bronchial asthma [42]. Potential protectiveness of rs1801133 variant allele in end stage renal crisis was mentioned throughout meta-analysis by Chang et al, however, results were contradictory among different populations [43]. Even though GCs were not our primary focus, this study showed that MTHFR rs1801133 might serve as a predictor of GCs response and should be further validated as such.…”

Section: Discussionmentioning

confidence: 99%

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Jelovac,

Kotur,

Ristivojevic

et al. 2023

IJMS

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Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 were tested for association with severe disease outcomes in 102 patients with SSc from Serbia treated either with immunosuppressants azathioprine (AZA) and methotrexate (MTX) or with other types of medications. Genotyping was performed using PCR-RFLP and direct Sanger sequencing. R software was used for statistical analysis and development of polygenic risk score (PRS) model. Association was found between MTHFR rs1801133 and higher risk for elevated systolic pressure in all patients except those prescribed with MTX, and higher risk for kidney insufficiency in patients prescribed with other types of drugs. In patients treated with MTX, variant SLCO1B1 rs4149056 was protective against kidney insufficiency. For patients receiving MTX a trend was shown for having a higher PRS rank and elevated systolic pressure. Our results open a door wide for more extensive research on pharmacogenomics markers in patients with SSc. Altogether, pharmacogenomics markers could predict the outcome of patients with SSc and help in prevention of adverse drug reactions.

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“…5E). Previous reports show that Rab3c modulates the IL6-STAT3 pathway 36 , which is critical for glucose homeostasis in hepatic tissue and skeletal muscle 37 . These results, along with their high expression of genes encoding receptors for the satiety hormones GLP-1 and leptin (Glp1r, Lepr) suggest that n11.Trh/Cxcl12 neurons may have a role in energy balance (Fig.…”

Section: Rampant Characterizes the Transcriptional Response To Metabo...mentioning

confidence: 99%

Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety

Webster,

Becker,

et al. 2023

Preprint

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SUMMARYLiraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. GLP-1RAs inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc) but only indirectly, implicating synaptic afferents to AgRP neurons. To investigate, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics. Applying this method to AgRP neurons in mice predicts 21 afferent subtypes in the mediobasal and paraventricular hypothalamus. Among these areTrh+Arc neurons (TrhArc), which express theGlp1rgene and are activated by the GLP-1RA liraglutide. Activating TrhArcneurons inhibits AgRP neurons and decreases feeding in an AgRP neuron-dependent manner. Silencing TrhArcneurons increases feeding and body weight and reduces liraglutide’s satiating effects. Our results thus demonstrate a widely applicable method for molecular connectomics, reveal the molecular organization of AgRP neuron afferents, and shed light on a neurocircuit through which GLP-1RAs suppress appetite.

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Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease

Abstract: Supplemental Digital Content is available in the text

Cited by 5 publications

References 106 publications

M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B

M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety

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