Haplotype analysis on association between C-reactive protein gene and susceptibility to type 2 diabetes mellitus in Chinese Han population : CRP gene and type 2 diabetes mellitus.

AIMS: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). METHODS: SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis. RESULTS: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047. CONCLUSIONS: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

Bioinformatics analysis reveals the potential role of matrix metalloproteinases in immunity and urolithiasis.

Background: The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall's plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation. Methods: The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA. Results: Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis. Conclusion: We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.

Multisensory Exercise Improves Balance in People with Balance Disorders: A Systematic Review.

OBJECTIVE: To examine the effect of multisensory exercise on balance disorders. METHODS: PubMed, Scopus and Web of Science were searched to identify eligible studies published before January 1, 2020. Eligible studies included randomized control trials (RCTs), non-randomized studies, case-control studies, and cohort studies. The methodological quality of the included studies was evaluated using JBI Critical Appraisal Checklists for RCTs and for Quasi-Experimental Studies by two researchers independently. A narrative synthesis of intervention characteristics and health-related outcomes was performed. RESULTS: A total of 11 non-randomized studies and 9 RCTs were eligible, including 667 participants. The results supported our assumption that multisensory exercise improved balance in people with balance disorders. All of the 20 studies were believed to be of high or moderate quality. CONCLUSION: Our study confirmed that multisensory exercise was effective in improving balance in people with balance disorders. Multisensory exercises could lower the risk of fall and enhance confidence level to improve the quality of life. Further research is needed to investigate the optimal strategy of multisensory exercises and explore the underlying neural and molecular mechanisms of balance improvement brought by multisensory exercises.

Pentamethylquercetin Inhibits Hepatocellular Carcinoma Progression and Adipocytes-induced PD-L1 Expression via IFN-γ Signaling.

BACKGROUND: Obesity is a significant risk factor for the development of types of cancer. Programmed death 1 and its ligand programmed death-ligand 1 (PD-L1) play a crucial role in tumor immune escape. Although, the role of PD-L1 in obesity-associated hepatocellular carcinoma (HCC) remains unknown. We previously showed that the natural flavonoid pentamethylquercetin (PMQ) possesses anti-obesity properties. OBJECTIVE: This study was designed to investigate the effects of PMQ on the development of HCC in obese mice and whether PMQ regulates PD-L1 and expression in HCC. METHODS: Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells. Tumor volumes and weights were measured. In vitro, 3T3-L1 preadipocytes were differentiated and lipid accumulation was measured by oil-red staining, and IFN-γ level was detected by Elisa. Hepatoma HepG2 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Western blotting was applied to detect PD-L1 protein levels in tumor tissue and HepG2 cells. RESULTS: Compared with control mice, H22 tumors grew faster and exhibited higher PD-L1 protein levels in obese mice. PMQ inhibited H22 tumor growth and reduced PD-L1 expression in tumor tissues. PD-L1 protein level was elevated in adi-CM-treated HepG2 cells. IFN-γ was detectable in adi-CM and exogenous IFN-γ induced PD-L1 expression in HepG2 cells. PMQ affected the differentiation of 3T3-L1 preadipocytes, decreased the level of IFN-γ secreted by adipocytes and downregulated adi-CM-induced PD-L1 expression in HepG2 cells. CONCLUSION: PMQ could inhibit HCC progression in obese mice at least in part through down-regulating adipocytes-induced PD-L1 expression via IFN-γ signaling.

Light Cupula: To Be Or Not to Be?

Benign paroxysmal positional vertigo (BPPV) represents the most common form of positional vertigo. It is caused by dislodged otoconia that freely float in the semicircular canals (canalolithiasis) or attach to the cupula (cupulolithiasis). A cupulolithiasis-type (or a heavy cupula-type) of BPPV implicating the lateral semicircular canal (LSCC) exhibits persistent ageotropic direction-changing positional nystagmus (DCPN) in a head-roll test. However, in some cases, unlike any type of BPPV, persistent geotropic DCPN cannot be explained by any mechanisms of BPPV, and don't fit the current classifications. Recently, the notion of light cupula has been introduced to refer to the persistent geotropic DCPN. In this study, we looked at the clinical features of light cuplula and discussed the possible mechanisms and therapeutic strategies of the condition. The notion of light cupula is a helpful addition to the theory of peripheral positional vertigo and nystagmus.

Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer.

INTRODUCTION: long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in urothelial carcinoma of the bladder (UCB) is just beginning to be studied. In this study, we focused on lncRNA SPRY4-IT1 and investigated its expression pattern, clinical significance, and biological function in UCB. METHODS: SPRY4-IT1 expression in UCB tissues was examined by quantitative Real-time PCR (qRT-PCR) and its correlation with clinicopathological features and patient prognosis was later analyzed. Moreover, in vitro assays were performed to explore its role in bladder cancer progression. RESULTS: SPRY4-IT1 expression was elevated in UCB tissues, and SPRY4-IT1 levels were highly positively correlated with histological grade, tumor stage, and lymph node metastasis and reduced overall survival. A multivariate analysis showed that SPRY4-IT1 expression is an independent prognostic factor of overall survival in patients with UCB. Additionally, the results of in vitro assays showed that the suppression of SPRY4-IT1 expression in bladder cancer cells significantly inhibit cell proliferation, migration, and invasion. CONCLUSIONS: Our data suggested that lncRNA SPRY4-IT1 is a novel molecule involved in bladder cancer progression, which provide a potential prognostic biomarker and therapeutic target.