Causal relationship association of cheese intake with gestational hypertension and diabetes result from a Mendelian randomization study.

BACKGROUND: The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes. AIM: To determine whether cheese consumption was causally related to hypertension and diabetes during pregnancy. METHODS: This was a two-sample Mendelian randomized (MR) study. Summary-level genetic data for cheese intake was exposure and corresponding outcome data for gestational hypertension and gestational diabetes were extracted from the IEU OpenGWAS database. MR analysis was conducted using inverse variance weighting. For sensitivity analyses, MR-Egger regression, weighted median, weighted mode, and leave-one-out methods were conducted. A fixed-effect model was used to meta-analyze two sample MR estimates. The traits of gestational hypertension were pregnancy hypertension (123579 individuals) and oedema, proteinuria and hypertensive disorders in pregnancy, childbirth and the puerperium (123579 individuals), and traits of gestational diabetes were gestational diabetes (123579 individuals) and diabetes mellitus in pregnancy (116363 individuals), respectively. RESULTS: Cheese intake per standard deviation increase has causally reduced the risks of gestational hypertension [odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.47-0.76, P < 0.001] and gestational diabetes (OR = 0.41, 95%CI: 0.30-0.55, P < 0.001) in inverse variance weighted analysis. Sensitivity analysis showed no heterogeneity (all P > 0.05) nor horizontal pleiotropy (all P > 0.05) in the relationship between cheese intake and gestational hypertension, but heterogeneity presented (all P < 0.05) in relation to gestational diabetes in the two-sample MR analysis. CONCLUSION: Cheese intake was inversely associated with gestational hypertension and gestational diabetes in MR analysis, suggesting that cheese consumption may be beneficial in preventing hypertension and diabetes during pregnancy.

Stable seasonal migration patterns in giant pandas.

A critical function of animal movement is to maximize access to essential resources in temporally fluctuating and spatially heterogeneous environments. Seasonally mediated resource fluctuations may influence animal movements, enabling them to track changing resource distributions, resulting in annual migration patterns. The conservation-dependent giant panda ( Ailuropoda melanoleuca) displays seasonal movement patterns; however, the key factor driving these seasonal migration patterns remains poorly understood. Here, we used GPS tracking collars to monitor the movements of six giant pandas over a 12-year period across different elevations, and performed statistical analysis of seasonal migration directions, routes, habitat revisitation, home range overlap, first arrival events, and stability. Our results revealed a compelling pattern of seasonal migrations that facilitated the ability of the pandas to forage at the appropriate time and place to maximize nutritional intake. Our results indicated that pandas utilize spatial memory to locate reliable food resources, as evidenced by their annual return to the same or similar winter and summer home ranges and the consistently maintained percentage of home range overlap. These novel insights into giant panda foraging and movement ecology not only enhance our understanding of its ability to adapt to nutritionally poor dietary resources but also provide important information for the development of resource utilization-based protection and management strategies.

Anti-inflammation treatment for protection of hepatocytes and amelioration of hepatic fibrosis in rats.

Chronic inflammation is considered as an important pathophysiologic mechanism of hepatic cirrhosis, which induces hepatocyte injury and activates hepatic stellate cells (HSCs), thus resulting in hepatic fibrosis. Previous studies have reported that cyclooxygenase-2 (COX-2) inhibitor can effectively treat liver fibrosis, while somatostatin (SST) analogues inhibit the activation of HSCs. The present study aimed to investigate the effects of a COX-2 inhibitor, celecoxib, combined with a SST analogue, octreotide, for protection of hepatocytes and prevention of fibrosis in a rat model of hepatic fibrosis. Therefore, a hepatic fibrosis rat model was established following peritoneal injection of thioacetamide (TAA), and the rats were then treated with a combination of celecoxib and octreotide (TAA + C). Immunohistochemistry and western blotting assays were used to assess the expression levels of proteins associated with inflammation, epithelial-mesenchymal transition (EMT), proliferation, apoptosis and autophagy. H&E staining, transmission electron microscopy and scanning electron microscopy were used to evaluate the destruction of hepatocytes. Masson's Trichrome and Sirius Red were used to measure the degree of liver fibrosis. The results demonstrated that, compared with those of the control group, the degree of liver fibrosis and the expression of the intrahepatic inflammation factors were aggravated in the TAA group. Furthermore, the apoptosis rate, EMT and autophagy of hepatocytes were also increased in the TAA group. However, treatment with TAA + C restored the aforementioned increased levels compared with the TAA group. In conclusion, treatment of rats with the combination of celecoxib and octreotide could attenuate the progress of hepatic fibrosis via protection of hepatocytes by reducing apoptosis, EMT and autophagy in hepatocytes.

Comparison of the serum metabolic signatures based on 1H NMR between patients and a rat model of deep vein thrombosis.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) have high morbidity, reduce quality of life, and can cause death. Biomarkers or genetic risk factors have not been identified in patients with DVT. In present study, serum of 61 patients suffering from DVT and a rat DVT model (n = 10) were assayed by a proton nuclear magnetic resonance (1H NMR) metabolomics technique combing with multivariate statistical analysis to identify the metabolites. The MetPA platform was used to identify differences in the metabolic pathways between the rat model and patients. The metabolomics results discovered that 11 different metabolites in rats and 20 different metabolites in DVT patients. Seven metabolites both altered in the rats and patients. Moreover, we observed changes in the metabolic pathways, including carbohydrate metabolism, lipid metabolism, and amino acid metabolism that were induced immediately by the thrombosis. Pathway of aminoacyl-tRNA biosynthesis perturbed only in the patients which was associated with the genetic risk factor of DVT. The study demonstrated that serum 1H NMR metabolomics can be used to diagnose DVT in the clinic. The altered pathways related to thrombosis and genetics will provide a foundation and new strategies for understanding the pathological mechanism and pharmacological targets of DVT.

Altered microRNA expression in skeletal muscle results from high-fat diet-induced insulin resistance in mice.

Skeletal muscle insulin resistance induced by a high-fat diet has been implicated in the development of type 2 diabetes. However, the precise molecular mechanisms involved are only partially understood. Recently, studies have shown that microRNAs play an important role in insulin resistance in various tissues. In this study, microRNA expression profiles of skeletal muscle of mice fed a high-fat or normal diet were analyzed using microarrays and the results were confirmed by real-time reverse-transcription polymerase chain reaction. Gene Ontology (GO) and pathway mapping tools were employed to analyze systemically the biological processes and signaling pathways affected by the differential expression of microRNAs. In this study, we show that 30 microRNAs are differentially expressed between 2 groups of mice. Compared to the mice fed a normal diet, there were 8 microRNAs up-regulated and 22 microRNAs down-regulated in the high-fat diet-fed mice. Furthermore, we confirm that the MAPK signaling pathway highlighted in this study is involved in skeletal muscle insulin resistance. These results indicate that skeletal muscle insulin resistance induced by a high-fat diet is associated with a group of microRNAs. GO and pathway mapping are a valid and effective approach for analyzing the function of microRNAs and the results could be a guideline for further investigation.

Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression.

Previous studies have shown decreased expression of repulsive guidance molecule member A (RGMa) in colorectal cancer. However, the relationship between the expression levels and promoter DNA methylation status of RGMa and the clinical characteristics of colorectal cancer has not been previously reported. Here, we investigated the expression of RGMa by immunohistochemistry, real-time PCR and western blotting and analyzed the methylation status of the RGMa promoter using Sequenom's MassARRAY platform in colorectal cancer tissues and adjacent normal colorectal tissues. The results showed that RGMa expression was decreased in cancer tissues compared with adjacent normal tissues (p<0.01). Furthermore, a tendency for decreased expression in tumor tissues was observed from Dukes' stage A to stage D (p<0.01). In addition, significantly higher levels of hypermethylation in promoter regions of RGMa were observed in colorectal cancer tissues, compared with those in adjacent normal colorectal tissues (p<0.01). Moreover, the methylation levels of RGMa in tumor tissues were significantly increased in Dukes' stage C and D compared with Dukes' stage A and B (p<0.01). Our results indicate that RGMa expression and promoter methylation status are closely related to colorectal cancer genesis and progression. Determination of the expression level and methylation frequency of RGMa in colorectal cancer tissues may have benefit for early diagnosis and for evaluating patient prognosis.