Obesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. The instrumental variables were SNPs associated with obesity as measured by body mass index (BMI) reported by GIANT consortium. The spectrum of outcome consisted of the phenotypes from published GWAS and the UK Biobank. The MR-Egger intercept test was applied to estimate horizontal pleiotropic effects, along with Cochran’s Q test to assess heterogeneity among the causal effects of instrumental variables. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis. Intriguingly, the effects that higher BMI could decrease the risk of both skin and prostate cancers, reduce calorie intake, and increase the portion size warrant further studies. Our results shed light on a novel mechanism of the disease-causing roles of obesity.

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Background: The association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene-environment synergistic effect have not been extensively examined in, therefore, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene-environment synergy effect and the risk of DN. Methods: Genotyping for 4 SNPs was performed with polymerase chain reaction (PCR) and following restriction fragment length polymorphism (RFLP) methods. Hardy-Weinberg balance of the control group was tested by SNPstats (online software: http://bioin fo.icono logia .net/snpst ats). The best combination of four SNPs of ELMO1 gene and environmental factors was screened by GMDR model. Logistic regression was used to calculating the OR values between different genotypes of ELMO1 gene and DN. Results: The rs741301-G allele and the rs10255208-GG genotype were associated with an increased risk of DN risk, adjusted ORs (95% CI) were 1.75 (1.19-2.28) and 1.41 (1.06-1.92), respectively, both p-values were < 0.001. We also found that the others SNPs-rs1345365 and rs7782979 were not significantly associated with susceptibility to DN. GMDR model found a significant gene-alcohol drinking interaction combination (p = 0.0107), but no significant gene-hypertension interaction combinations. Alcohol drinkers with rs741301-AG/GG genotype also have the highest DN risk, compared to never drinkers with rs741301-AA genotype, OR (95% CI) 3.52 (1.93-4.98). Conclusions: The rs741301-G allele and the rs10255208-GG genotype, gene-environment interaction between rs741301 and alcohol drinking were all associated with increased DN risk.

As the scale and depth of artificial intelligence network models continue to increase, their accuracy in albumin recognition tasks has increased rapidly. However, today’s small medical datasets are the main reason for the poor recognition of artificial intelligence techniques in this area. The sample size in this article is based on the data analysis and research on urine albumin detection of diabetes in the EI database. It is assumed that the observation group has at least 20 mg UAER difference from the control group, and the standard deviation of the UAER change from baseline to 12 weeks is 30 mg. Therefore, the sample size of the two groups is 77 cases. Assuming that the rate of loss to follow-up during the follow-up period is 20%, at least 92 patients are needed. The final enrollment in this study is 100 patients. Studies have shown that DR is used as an indicator to diagnose NDRD, and its OR value is as high as 28.198, indicating that non-DR can be used as an indicator to distinguish DN from NDRD. The meta-analysis found that DR has a sensitivity of 0.65 and a specificity of 0.75 in distinguishing DN from NDRD in patients with type 2 diabetes, and it is emphasized that PDR is highly specific in the diagnosis of DN. Using a meta-analysis to systematically analyze 45 studies, it was found that the sensitivity of DR to diagnose DN was 0.67, the specificity was 0.78, and the specificity of PDR to predict DN was 0.99, indicating that DR is a good indicator for predicting DN, and the team’s latest research has also verified this point of view. They have established a new model for diagnosing DN. In addition to including traditional proteinuria, glycosylated hemoglobin, FR, blood pressure, and other indicators into the diagnostic model, it will also include the presence or absence of DR. The final external verification accuracy rate of this model is 0.875.

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Long non-coding RNA (lncRNA) actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), shows crucial regulatory function in tumor progression. Nonetheless, the biological function and underlying mechanism of AFAP1-AS1 in the progression of thyroid cancer is still unclear. Expressions of AFAP1-AS1, miR-204-3p, and DUSP4 were quantified utilizing qRT-PCR and/or Western blot. In loss-of-function and gain-of-function assays, cell proliferation, migration and invasion were appraised by CCK-8 assay, wound healing assay, Transwell migration and invasion assays, respectively. Luciferase reporter assay was employed for validating the interaction between miR-204-3p and AFAP1-AS1 or the 3’UTR of dual specificity phosphatase 4 (DUSP4). AFAP1-AS1 was highly expressed in thyroid cancer tissues and cell lines. Highly expressed AFAP1-AS1 was in association with advanced TNM stage and positive lymph node metastasis. Knockdown of AFAP1-AS1 suppressed the proliferation, migration and invasion of thyroid cancer cells, and overexpression of AFAP1-AS1 induced a reversed effect. MiR-204-3p was targetedly repressed by AFAP1-AS1, and miR-204-3p could negatively regulate DUSP4 expression. AFAP1-AS1 augmented the expression of DUSP4 via repressing miR-204-3p, and the effects of AFAP1-AS1 overexpression on thyroid cancer cells were also partly abolished by miR-204-3p restoration. In summary, AFAP1-AS1 facilitates thyroid cancer cell proliferation, migration, and invasion by regulating miR-204-3p/DUSP4 axis.

Previous studies have demonstrated that valproic acid (VPa), a histone deacetylase inhibitor, alleviates diabetic nephropathy (dn). However, the biological mechanisms underlying this protective effect remains unclear. This study aimed to investigate the effects of histone deacetylase inhibitor VPa on hyperglycemic induction of nrK-52e cell erS and apoptosis. endoplasmic reticulum stress (erS)-related apoptosis is involved in dn, and improving erS may delay the symptoms of dn. Histone deacetylase regulates gene transcription or expression of erS-related proteins. The present study established an erS model by treating the rat renal tubular epithelial cells nrK-52e with high glucose (HG) and investigated the effects of VPa on the apoptosis of the nrK-52e cells. HG stimulation significantly increased the protein levels of the ERS-related proteins including glucose regulated protein 78 (GrP78), activating transcription factor 4 (aTF4), c/eBP homologous protein (cHoP), caspase-12 and phosphorylated (p)-JnK. VPa treatment further upregulated GrP78 expression and attenuated the levels of aTF4, cHoP, caspase-12 and p-JnK. notably, HG markedly promoted apoptosis of nrK-52e cells by regulating the protein levels of Bax, cleaved caspase-3 and Bcl-2, which was attenuated by simultaneous VPa treatment. Mechanistically, VPa increased the total acetylation levels of histone H4 in nrK-52e cells and increased the histone H4 acetylation of the GrP78 promoter region. in conclusion, VPa attenuated HG-induced erS and apoptosis in nrK-52e cells, which may be due to the regulation of acetylation levels of erS-related proteins. in addition, the present study suggested that Hdacis are promising drugs for treating patients with dn.

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