The clinical significance of circulating miR-21, miR-142, miR-143, and miR-146a in patients with prostate cancer

BackgroundProstate cancer (PCa) is the most common type of solid tissue cancer among men in western countries. In this study, we determined the levels of circulating miR-21, miR-142, miR-143, miR-146a, and RNU 44 levels as controls for early diagnosis of PCa.MethodsThe circulating miRNA levels in peripheral blood samples from 43 localized PCa patients, 12 metastatic PCa (MET) patients, and a control group of, 42 benign prostate hyperplasia (BPH) patients with a total of 97 volunteers were determined the by PCR method.ResultsNo differences in the DCT values were found among the groups. In PCa and PCaMet groups the expression of miR21 and miR142 were higher compared to the BHP group. No other differences were observed among the other groups. miR21 expression in the PCa group was 6.29 folds upregulated whereas in the PCaMet group 10.84 folds up-regulated. When the total expression of miR142 is evaluated, it showed a positive correlation with mir21 and mir 146 (both p<0.001). Also, the expression of miR146 shows a positive correlation with both miR21 and miR143 (both p<0.001). Expression of miRNAs was found to be an independent diagnostic factor in patients with Gleason score, PSA, and free PSA levels.ConclusionsOur study showed that co-expression of miR21, miR-142, miR-143, and miR-146a and the upregulation of miR-21 resulted in increased prostate carcinoma cell growth. In the PCaMet group, miR21 is the most upregulated of all miRNAs. These markers may provide a novel diagnostic tool to help diagnose PCa with aggressive behavior.     

骨碎补对骨性关节炎患者骨关节滑膜组织中miR-27a、miR-146a表达的影响

目的:探讨骨碎补对骨性关节炎患者骨关节滑膜组织中mi R-27a、mi R-146a表达的影响。方法:选取我院收治的骨性关节炎患者46例,随机分为两组,每组各23例。对照组予抗骨增生治疗,实验组在对照组基础上加以骨碎补治疗。观察和比较两组患者的临床疗效、炎性因子水平的变化以及骨关节滑膜组织中mi R-27a、mi R-146a的表达情况。结果:1治疗后,两组患者的临床症状均有所改善,且实验组疗效高于对照组,差异有统计学意义(P0.05)。2治疗后,两组患者的IL-1β、PGE2水平均较治疗前显著降低,且实验组降低较对照组更明显,差异均有统计学意义(P0.05)。3治疗后,两组患者的骨关节滑膜组织中的mi R-27a、mi R-146a表达均降低,且与对照组比较,实验组较低,差异有统计学意义(P0.05)。结论:骨碎补能够降低骨性关节炎患者骨关节滑膜组织中mi R-27a、mi R-146a的表达,降低IL-1β、PGE2的水平,提高临床疗效。     

Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene

ABSTRACT. Familial fatal insomnia (FFI) is fatal disorder characterized by damage to select thalamic nuclei, together with progressive insomnia and dysautonomia. In subjects carrying the D178N prion protein (PRNP) mutation, distinct phenotypes can be observed, depending on the methionine (Met) /valine (Val) codon 129 polymorphism. We report here a Chinese case of FFI with a D178N/Met129 genotype of the PRNP gene, who exhibited rapidly progressive dementia combined with behavioral disturbances and paroxysmal limb myoclonus. Our patient did not show refractory insomnia early in the disease course, nor demonstrate typical MRI and EEG alterations. There was remarkable family history of similar symptoms.     

microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis

Chronic apical periodontitis (CAP) is defined as chronic inflammation of the dental pulp and root canal system. Porphyromonas endodontalis lipopolysaccharide ( P. endodontalis LPS) plays an important role in inducing an inflammatory response in CAP. microRNA-146a (miR-146a) is a key regulator of inflammation and is induced by LPS. Hairy and enhancer-of-split related with YRPW motif 2 (Hey2) has been confirmed to be induced by the Notch signaling pathway, which is involved in tooth development, pulp regeneration, and repair after injury. Our study aimed to investigate the functional role of miR-146a via the targeting of Hey2 in CAP as well as the underlying mechanism. Compared with 13 healthy controls, miR-146a and Hey2 expressions were significantly higher in 20 patients with CAP. In addition, miR-146a, Hey2, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α expressions were significantly increased in MC3T3-E1 cells stimulated with different concentrations (0-20 μg/mL) of P. endodontalis LPS for different amounts of time (0-48 hours). Moreover, miR-146a, which acts as an anti-inflammatory mediator, negatively regulated the expression of IL-6, IL-1β, and TNF-α, and Hey2 was confirmed as a target gene of miR-146a by a luciferase reporter assay. Hey2 also negatively regulated miR-146a, IL-6, IL-1β, and TNF-α expressions, and P. endodontalis LPS strongly induced Hey2 recruitment to the IL-6 promoter (−400 ~ −200 bp). These findings suggest that miR-146a and Hey2 form a mutual negative feedback regulatory loop, demonstrating a novel mechanism that regulates inflammatory responses in CAP.     

特应性皮炎患儿外周血miR-122a和miR-146a水平与Th1/Th2/Th17免疫平衡的相关性分析

摘要 目的：探讨特应性皮炎（AD）患儿外周血微小核糖核酸（miRNA）-122a和miR-146a水平与辅助性T细胞（Th）1/Th2/Th17免疫平衡的相关性。方法：选取2020年5月～2023年5月石家庄市妇幼保健院皮肤科收治的AD患儿100例为AD组,根据特应性皮炎评分（SCORAD）分为轻度组31例、中度组41例、重度组28例,另选取同期100名体检健康儿童为对照组。采用实时荧光定量聚合酶链式反应检测外周血miR-122a、miR-146a水平,流式细胞术检测外周血Th1、Th2、Th17细胞比例,酶联免疫吸附法检测外周血Th1、Th2、Th17相关细胞因子[白细胞介素（IL）-2、干扰素-γ（IFN-γ）、IL-4、IL-13、IL-17、IL-22]水平,并计算Th1/Th2/Th17比值。采用Pearson/Spearman相关性分析AD患儿外周血miR-122a、miR-146a与Th1、Th2、Th17和相关细胞因子及Th1/Th2/Th17的相关性。结果：AD组外周血miR-122a、miR-146a、Th1、Th1/Th2/Th17、IL-2、IFN-γ水平低于对照组,Th2、Th17、IL-4、IL-13、IL-17、IL-22水平高于对照组（P均＜0.05）。轻度组、中度组、重度组外周血miR-122a、miR-146a、Th1、Th1/Th2/Th17、IL-2、IFN-γ水平依次降低,Th2、Th17、IL-4、IL-13、IL-17、IL-22水平依次升高（P均＜0.05）。Pearson/Spearman相关性分析显示,AD患儿外周血miR-122a、miR-146a与Th1、Th1/Th2/Th17、IL-2、IFN-γ水平呈正相关（r/rs分别为0.679、0.677、0.684、0.706、0.693、0.689、0.671、0.694,P均＜0.001）,与Th2、Th17、IL-4、IL-13、IL-17、IL-22呈负相关（r/rs分别为-0.690、-0.680、-0.681、-0.669、-0.675、-0.676、-0.676、-0.686、-0.682、-0.674、-0.680、-0.689,P均＜0.001）。结论：AD患儿外周血miR-122a、miR-146a水平降低,与病情严重程度密切相关,可能通过调节Th1/Th2/Th17免疫平衡参与AD发生发展。     

PVT1 (rs13281615) and miR-146a (rs2910164) polymorphisms affect the prognosis of colon cancer by regulating COX2 expression and cell apoptosis

In this study, we aimed to investigate the potential correlation between rs13281615/rs2910164 polymorphisms and the prognosis of colon cancer (CC). Taqman was utilized to genotype the rs13281615/rs2910164 polymorphisms in recruited subjects. Kaplan–Meier survival curves were calculated to study the prognostic values of different genotypes of rs13281615/rs2910164 polymorphisms. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays were conducted to establish a potential signaling pathway underlying the role of rs13281615/rs2910164 polymorphisms, whereas bioinformatics analysis and luciferase reporter assays were performed to identify plasmacytoma variant translocation 1 (PVT1) and cyclooxygenase-2 (COX2) as targets of microRNA-146a (miR-146a). No significant difference was observed in respect to clinical characteristics among subjects with different genotypes. However, patients genotyped as GG/CC + GC showed the lowest chance of survival, whereas patients of GA + AA/GG genotype showed the highest chance of survival. Moreover, the relative expressions of PVT1, prostaglandin E2 (PGE2), and COX2 were the lowest and the relative expression of miR-146a was the highest in GA + AA/GG subjects, validating the roles of PVT1, miR-146a, and COX2 in CC. In addition, both PVT1 and COX2 were identified as virtual targets of miR-146a, and the luciferase activities of cells cotransfected with wild-type PVT1/COX2 and miR-146a mimics were significantly reduced. Moreover, the presence of PVT1 decreased the level of miR-146a whereas increasing the messenger RNA and protein levels of COX2, thus establishing a PVT1/miR-146a/COX2 signaling pathway underlying the pathogenesis of CC. The presence of rs13281615 G > A polymorphism on PVT1 and the rs2910164 C > G polymorphism on miR-146a contributes to a favorable prognosis in CC patients via modulating the activity of the PVT1/miR-146a/COX2 signaling pathway.     

A novel missense mutation of the ATP2C1 gene in a Chinese patient with Hailey-Hailey disease

Benign familial chronic pemphigus (Hailey–Hailey disease, HHD; MIM 169600) is a rare autosomal dominant hereditary disorder characterized by pruritic vesicles, painful erosions and scaly erythematous plaques at the sites of friction and flexures. Mutations in ATP2C1, which encoding the human secretory pathway Ca²⁺/Mn²⁺-ATPase protein 1 (hSPCA1), have been identified as the pathogenic gene of HHD. We found a novel, distinct, heterozygous mutation during study of a Chinese patient with HHD. We identified a C→T transition at nucleotide 1235 (p.Thr352IIe), in exon 13 of ATP2C1. This observation would be useful for genetic counseling and prenatal diagnosis for affected families and in expanding the repertoire of ATP2C1 mutations underlying HHD.     

The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease

Background

Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case–control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed.

Methods

The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR–RFLP assay. Anthropometric measurements were measured in all participants.

Results

There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p = 0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA + AA genotypes in male CHD patients (p = 0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age < 55 (OR = 2.837, p = 0.001) and TC ≥ 5.18 mmol/L (OR = 1.970, p = 0.027) in male subjects. However, this association was not observed in female patients (p > 0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age < 55 years.

Conclusion

These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.     

Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients

Background

Hepatogenous diabetes (HD) occurs as a complication of cirrhosis. Whether genetic factors, rather than only liver damage, play roles in the development of HD is unknown. TCF7L2 gene has been reported to be associated with type 2 diabetes and also cancer risks. We aim to evaluate the impact of TCF7L2 gene on the susceptibility of HD and hepatocellular carcinoma (HCC) in a Chinese Han population.

Patients and methods

A total of 367 adult liver transplant candidates with liver cirrhosis were included. Fifteen tag single nucleotide polymorphisms (SNPs) were selected from HapMap CHB database with a minor allele frequency of > 0.2 and r² of > 0.8. Another three SNPs were also chosen because of their close association with type 2 diabetes in East Asian.

Results

Patients with HD presented significantly poorer liver function, higher incidence of cirrhotic complications and higher insulin resistance compared with non-HD patients. Three SNPs were differentially distributed between HD patients and non-HD patients. In multivariate logistic analysis, TCF7L2 rs290487 and rs6585194 polymorphisms were independently associated with HD after adjustment of clinical factors. The TCF7L2 rs290487 C/C variant homozygote showed much higher insulin resistance and significantly increased HD risk comparing with T/T and T/C genotypes, while the genetic variant of rs6585194 was protectively against HD. Three SNPs (rs290481, rs290487 and rs290489) located near the 3′ end of TCF7L2 gene were associated with HCC risk with marginal significance. Patients carrying G-C-A haplotype had a significantly higher HCC risk than those with A-T-G.

Conclusions

TCF7L2 polymorphisms were associated with HD and maybe cancer risk as well. Further studies with large samples are needed to verify these results.     

Detection of somatic and germline mosaicism for the LAMP2 gene mutation c.808dupG in a Chinese family with Danon disease

Danon disease is a rare X-linked lysosomal storage disease characterized by hypertrophic cardiomyopathy, myopathy and mental retardation, and is due to a primary defect in lysosome-associated membrane protein-2 (LAMP 2). More than 26 mutations in the LAMP2 gene have been described, including a small number of de novo mutations, some of which are suspected to be caused by germline mosaicism. Here, we describe the first molecularly documented evidence of somatic mosaicism for a LAMP2 mutation, identified in the asymptomatic mother of a boy with Danon disease caused by the frameshift mutation c.808dupG (p.A270Gfx3) within exon 6. In addition, in order to gain insight into the possible explanation for the mother's lack of phenotype, the level of somatic mosaicism and the X-chromosome inactivation pattern were investigated. This study provides new insight into the causes of phenotypic variability in female mutation-carriers and underlines the importance of parental molecular testing for accurate genetic counseling for Danon disease.     

A case-control study between the gene polymorphisms of polyunsaturated fatty acids metabolic rate-limiting enzymes and coronary artery disease in a Chinese Han population

To investigate the association between the polymorphisms of fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2) and elongation of very long chain fatty acids like 2 (ELOVL2) gene and coronary artery disease (CAD) in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) from these genes were genotyped using PCR-based restriction fragment length polymorphism analysis in 199 CAD cases and 192 controls of Han Chinese origin. rs174556 in the FADS1 gene showed allelic (P=0.002) and genotypic (P=0.030) association with the disease, while there was no disease association for the other two SNPs. The frequency of rs174556 minor allele (T) was significantly higher in the case group than the control group. The trans phase gene–gene interaction analysis showed that the combined genotype of rs174556 (T/T) and rs3756963 (T/T) was weakly associated with the disease (P=0.043). rs174556 in the FADS1 gene is very likely to be associated with CAD in the Chinese Han population.     

HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies,acute phase reactants,cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients

Introduction  

The revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity (autoantibodies, acute phase reactants and cytokines).     

Analysis of a silkworm F1 hybrid with yellow cocoon generated by crossing two white-cocoon strains: Further evidences for the roles of Cameo2 and CBP in formation of yellow cocoon

In this report, we examined the gene expression related to carotenoid transport for a silkworm F₁ hybrid with yellow cocoon generated by crossing two white-cocoon strains, Qiubai and 12-260. Our results showed that, in Qiubai, Cameo2, a transmembrane protein gene belonging to the CD36 family genes, was expressed normally in the silk gland, but no intact carotenoid-binding protein (CBP) mRNA (only the truncated CBP mRNA) was detected in the midgut. In 12-260, we detected the intact CBP mRNA expression in the midgut, but no Cameo2 expression in the silk gland. Regarding the F₁ hybrid from crossing Qiubai and 12-260, both Cameo2 and intact CBP mRNA expressed normally in the silk gland and midgut. HPLC detection confirmed that in the F₁ hybrid the carotenoids could be absorbed from dietary mulberry leaves through the midgut and transferred to silk gland via the hemolymph, which eventually colored cocoons into yellow. We also identified four CBP mRNA isoforms expressed in the midgut of the F₁ hybrid, subsequently named as variants 5–8. Our results provide further evidences for the roles of Cameo2 and CBP in the formation of yellow cocoon of silkworm.     

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study

BackgroundCardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn’t been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state.MethodsThis is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls).ResultssP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases.ConclusionOur study supports the previous researches’ results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.