CFTR gene mutations and polymorphism are associated with non-obstructive azoospermia: From case-control study

Publication date: 30 August 2017
Source:Gene, Volume 626
Author(s): Lingying Jiang, Jiamin Jin, Shasha Wang, Fuxing Zhang, Yongdong Dai, Libing Shi, Songying Zhang
A variety of experimental studies have yielded evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) protein participates in the process of spermatogenesis. However, the association between CFTR gene and non-obstructive azoospermia (NOA) disease remained to be a question. First, we reviewed available data from the PubMed and Embase databases before May 2016 to find the most common mutations of CFTR gene in NOA patients. Second, an original case-control study was conducted on NOA patients (n=100) and a control group consisting of fertile males (n=100), selected from August 2015 to March 2017, to detect CFTR gene mutations and polymorphism. Peripheral blood samples from NOA patients and normal controls were analyzed for the presence of specific sequences of CFTR gene by polymerase chain reaction amplification followed by direct sequencing. From our comprehensive review, 12 case-control studies were found concerning the relation between CFTR gene mutations and polymorphism and NOA disease. Fifty-four mutations were mentioned and IVS8 poly-T, TG repeats, F508del and R117H mutations were the most common ones. Based on that, we detected IVS8 poly-T, TG repeats, F508del, R117H and M470V mutations in our case control study. We found that the T5 allele was present at a significantly higher rate in NOA patients than in the control group (5.00% versus 0.00%, p<0.01) with increased risk having NOA [Odds ratios (OR) 2.05, 95% confidence intervals (CI) 1.85–2.27]. The T5 variant was always accompanied by TG12 (10/10) and V470 allele participated in most TG12T5 haplotypes (8/10). TG12T5-V470 haplotype also enhanced risk of having NOA [OR 2.04, 95% CI 1.84–2.26]. F508del and R117H mutations were not found in either group. In conclusion, the polyvariant mutant genes of CFTR: T5 allele and TG12-T5-V470 genotype are correlated with NOA, but F508del and R117H mutations have low possibility to be associated with NOA.



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Genetic variants of interleukin-18 are associated with reduced risk of atrial fibrillation in a population from Northeast China

Publication date: 30 August 2017
Source:Gene, Volume 626
Author(s): Ying-Hui Wang, Lin Fu, Bo Wang, Shu-Feng Li, Zhao Sun, Ying Luan
Atrial fibrillation (AF) affects approximately 1–2% of general population. Chronic inflammation plays an important role in AF development and interleukin-18 (IL-18) is a pro-inflammatory cytokine. This study aimed to assess the association of single nucleotide polymorphisms (SNPs) of IL-18 for with AF risk. Blood samples were taken from 243 AF patients and 160 non-AF individuals from a Chinese population and subjected to genotyping for six IL-18 SNPs using the MassArray system. Association of individual SNPs with AF risk was analyzed using SAS version 9.1. The results showed that the left atrial diameter was increased and the left ventricular ejection fraction was decreased in AF patients compared to controls. IL-18 SNPs were associated with reduced risk of AF even after adjusting for various confounding factors. Specifically, rs187238 GC genotype and C allele, rs360719 AG genotype and G allele, and rs549908 GT genotype and G allele were associated with decreased risk of AF. In conclusion, our findings indicate that rs187238, rs360719, and rs549908 in IL-18 are associated with reduced risk of AF in this cohort of patients.



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MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma

Publication date: 30 August 2017
Source:Gene, Volume 626
Author(s): Wenjuan Liu, Honghong Li, Yan Wang, Xinyao Zhao, Yuanying Guo, Jing Jin, Rongxiang Chi
Increasing evidence has demonstrated that aberrant microRNAs (miRNAs) play important roles in the pathogenesis of most human malignancies. The purpose of this study was to explore the role of miR-30b-5p in human RCC. In the current study, we firstly found that the expression levels of miR-30b-5p were lower in both RCC tissues and cell lines. Then, we found that enforced miR-30b-5p expression and knockdown of GNA13 significantly suppressed the proliferation, invasion, migration and EMT of RCC cell lines. In addition, miR-30b-5p directly targeted GNA13 and repressed its expression. Furthermore, re-expression of GNA13 (without the 3′-UTR) could partially abrogate the miR-30b-5p-induced cell proliferation and metastasis inhibition. Taken together, these findings indicated that miR-30b-5p acts as a novel tumor suppressor to regulate RCC cell proliferation, metastasis and EMT through downregulation of GNA13 expression. Therefore, miR-30b-5p may be considered a potential biomarker for the diagnosis of RCC.



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When traditional cancer therapy doesn't work - WTAJ

WTAJ

When traditional cancer therapy doesn't work WTAJ Head and neck cancers are the sixth most common cancers worldwide, in large part due to the presence of the HPV virus. Now, researchers are testing an immunotherapy treatment they say is highly effective for patients with cancer that spreads or comes ...

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Characteristics and Outcomes of Patients with Profound Hyponatremia due to Primary Polydipsia

Abstract

Objective

Hyponatremia due to excessive fluid intake (i.e. primary polydipsia (PP)) is common. It may culminate in profound hyponatremia—carrying considerable risk of morbidity. However, data on patients with PP leading to hyponatremia is lacking. Herein, we describe the characteristics of polydiptic patients hospitalised with profound hyponatremia, and assess one-year outcomes.

Design

Substudy of the prospective observational Co-MED Study.

Patients

Patients with an episode of profound hyponatremia (≤125mmol/l) due to PP in the medical emergency were eligible and classified into psychogenic polydipsia (PsyP), dipsogenic polydipsia (DiP), and beer potomania (BP).

Measurements

Symptoms, laboratory findings, and factors contributing to hyponatremia (comorbidities, medication, and liquid intake) were assessed. A one-year follow-up was performed to evaluate recurrence of hyponatremia, re-admission rate, and mortality.

Results

23 patients were included (median age 56 years [IQR 50-65], 74% female), 7 had PsyP, 8 DiP, and 8 BP. Median serum sodium of all patients was 121mmol/l (IQR 114-123), median urine osmolality 167mmol/l (IQR 105-184), and median copeptin 3.6mmol/l (IQR 1.9-5.5). Psychiatric diagnosis, particularly dependency disorder (43%) and depression (35%), were highly prevalent. Factors provoking hyponatremia were found in all patients (e.g. acute water load, medication, stress).

During the follow-up period, 67% of patients were readmitted, 52% of these with re-hyponatremia, and 3 patients (38%) with BP died.

Conclusion

Patients with PP are more likely to be female, and have addictive and affective disorders. Given the high recurrence, re-hospitalisation, and mortality rate, careful monitoring and long-term follow-up including controls of serum sodium, education and behavioural therapy is needed.

This article is protected by copyright. All rights reserved.

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Sickle cell disease and implementation science: A partnership to accelerate advances

Abstract

Sickle cell disease (SCD) results in end organ damage and a shortened lifespan. Both the pathophysiology of the disease and the social determinants of health affect patient outcomes. Randomized controlled trials have been completed among this population and resulted in medical advances; however, the gestation of these advances and the lack of penetrance into clinical practice have limited advancements in clinical improvements for many people with SCD. We discuss the role of implementation science in SCD and highlight the need for this science to shorten the length of time to implement evidence-based care for more people with SCD.

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Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone

Abstract

Choline acetyltransferase-positive (ChAT⁺) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine. Mice subjected to MCAO exhibited elevated expression of cytomembrane and nuclear fibroblast growth factor receptor 1 (FGFR1), as well as increased expression of PI3K, pAkt, doublecortin (DCX), polysialylated - neuronal cell adhesion molecule (PSA-NCAM), and mammalian achaete-scute homolog 1 (Mash1). MCAO mice also had more glial fibrillary acidic protein (GFAP)/5-bromo-2′-deoxyuridine (BrdU)-positive cells and DCX-positive cells in the SVZ than did the sham-operated group. Methyllycaconitine treatment increased cytomembrane FGFR1 expression and GFAP/BrdU-positive cells, upregulated the levels of phosphoinositide 3-kinase (PI3K) and phospho-Akt (pAkt), decreased nuclear FGFR1 expression, decreased the number of DCX-positive cells, and reduced the levels of DCX, PSA-NCAM, and Mash1 in the SVZ of MCAO mice compared with levels in vehicle-treated MCAO mice. MCAO mice treated with α7 nAChR agonist PNU-282987 exhibited the opposite effects. Our data show that α7 nAChR may decrease the proliferation of neural stem cells and promote differentiation of existing neural stem cells after stroke. These results identify a new mechanism of SVZ ChAT⁺ neuron-induced neurogenesis.

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