Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

An immune-related prognostic signature associated with immune landscape and therapeutic responses in gastric cancer.

Immune-related genes (IRGs) have attracted attention in recent years as therapeutic targets in various tumors. However, the role of IRGs in gastric cancer (GC) has not been clearly elucidated. This study presents a comprehensive analysis exploring the clinical, molecular, immune, and drug response features characterizing the IRGs in GC. Data were acquired from the TCGA and GEO databases. The Cox regression analyses were performed to develop a prognostic risk signature. The genetic variants, immune infiltration, and drug responses associated with the risk signature were explored using bioinformatics methods. Lastly, the expression of the IRS was verified by qRT-PCR in cell lines. In this manner, an immune-related signature (IRS) was established based on 8 IRGs. According to the IRS, patients were divided into the low-risk group (LRG) and high-risk group (HRG). Compared with the HRG, the LRG was characterized by a better prognosis, high genomic instability, more CD8+ T cell infiltration, greater sensitivity to chemotherapeutic drugs, and greater likelihood of benefiting from the immunotherapy. Moreover, the expression result showed good consistency between the qRT-PCR and TCGA cohort. Our findings provide insights into the specific clinical and immune features underlying the IRS, which may be important for patient treatment.

Cryopreservation of black seabream (Acanthopagrus schlegelii) sperm.

In recent years, biotechnology has had a significant impact on the aquaculture industry, particularly in the field of breeding. Molecular selection breeding has emerged as a novel approach to breeding. Reducing the cost of genetic information for individuals with desirable traits after breeding has become an important research direction. Cryopreservation technology allows bypassing time and space constraints in genetic breeding, simplifying broodstock management. This study presents a detailed cryopreservation method for black seabream sperm, evaluating extender type, glucose concentration, cryoprotectant type and concentration, sperm-dilution ratio, and cooling protocols. Sperm motility parameters were analyzed using computer-assisted sperm analysis (CASA) before and after two days of freezing. This involved using an RS solution with a glucose concentration of 15 g/L and adding a 5% final concentration of EG as the sperm cryoprotectant. After mixing the sperm and solution at a ratio of 1:2, we subjected it to 5 min fumigation at 5 cm above the liquid nitrogen surface before plunging it into the nitrogen. Sperm motility reached 85.46 ± 7.32% after two days. Various enzymatic activities showed changes over 20 days post-cryopreservation. This improved cryopreservation protocol for black seabream sperm is beneficial for genetic breeding and reproduction and provides reference for studying the cryodamage mechanisms of black seabream sperm.

Transcriptomics Reveal the Effects of Breeding Temperature on Growth and Metabolism in the Early Developmental Stage of Platax teira.

The growth, development, and survival of fish, especially in the early stages of development, is influenced by a complex of environmental factors, among which temperature is one of the most important. Although the physiological effects of environmental stress in fish have been extensively studied, the molecular mechanisms are poorly understood. However, recent advances in transcriptomic techniques have facilitated the study of the molecular mechanisms of environmental stress responses in aquatic species. Here, we aimed to elucidate the effects of breeding temperatures (21, 24, 27, and 30 °C) on the growth and nutrient metabolism in the early developmental stage of Platax teira, using transcriptomic techniques. Transcriptomic analysis identified 5492, 6937, and 4246 differentially expressed genes (DEGs) in the 21 vs. 24 °C, 27 vs. 24 °C, and 30 vs. 24 °C comparisons, respectively, most of which were involved in cell processes, single organism, metabolism, catalytic activity, and cell part, based on gene ontology (GO) functional annotations. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were mainly enriched in pathways related to metabolism of matter and energy, protein digestion and absorption, and glucose and lipid metabolism. Additionally, the expression of genes related to energy, lipid, and glucose metabolism in the fish liver was upregulated under a low-temperature condition (21 °C), although increasing the temperature within the acceptable threshold improved nutrient metabolism and growth in the fish. Meanwhile, nutrient metabolism and growth were suppressed by an extremely high temperature (30 °C) owing to oxidative stress. Overall, it was shown that nutrient metabolism pathways were involved in thermal stress responses in P. teira, and the optimal breeding temperature range was 24-27 °C. Through transcriptomics, the regulatory mechanism of larval development in P. teira under different growth temperatures was elucidated, with the goal of establishing a theoretical basis for industrial breeding.

Fisetin Ameliorates Alcohol-Induced Liver Injury through Regulating SIRT1 and SphK1 Pathway.

Alcoholic liver disease (ALD) often leads to hepatitis, hepatic cirrhosis, and even hepatocellular carcinoma. Fisetin has been shown to confer protection against liver injury. Herein, we investigated whether fisetin could prevent ethanol-induced hepatotoxicity. Mice were fed on 5% (v/v) Lieber-DeCarli ethanol diet. Human primary hepatic stellate cells (HSCs) co-cultured with ethanol were used to verify the therapeutic effect of fisetin. The results of alanine/aspartate aminotransferase (ALT/AST), Triglyceride (TG), total cholesterol (TC) in serum, Oil O Red and Masson staining revealed that fisetin (80[Formula: see text]mg/kg) ameliorated ethanol-induced mice liver injury and fibrosis. Besides, immunofluorescence results of [Formula: see text]-SMA revealed that fisetin suppressed HSCs activation. The suppression was dose-dependent. Furthermore, fisetin promoted SIRT1-mediated autophagy and inhibited Sphk1-mediated endoplasmic reticulum stress (ER stress) both in vitro and in vivo. Molecular docking results indicated potential interaction of fisetin with SIRT1 and SphK1. The inhibitory effect of fisetin on HSCs activation was reversed on co-culturing with EX-527, a specific inhibitor against STIR1 overexpression. Thus, fisetin has the potential to ameliorate alcohol-induced liver injury through suppression of HSCs activation, SIRT1-mediated autophagy and Sphk1-mediated ER stress.

Identification and analysis of lipid droplet-related proteome in the adipose tissue of grass carp (Ctenopharyngodon idella) under fed and starved conditions.

Fat accumulation in the mesenteric adipose tissue is a serious problem in grass carp (Ctenopharyngodon idella) culture. Lipid droplet-related proteins (LDRPs) are involved in the formation, degradation, and biological functions of lipid droplets. In this study, we aimed to provide reference proteomics data to study lipid droplet regulation in fish. We isolated LDRPs from the mesenteric adipose tissue of grass carp (1-year-old) after normal feeding and 7 days of starvation, and identified and analysed them using isobaric tags for relative and absolute quantitation (iTRAQ) technology. Short-term starvation had no significant effect on the body weight, condition factor, visceral index, hepatopancreas index, intraperitoneal fat index, adipose tissue triglyceride content, and adipocyte size of grass carp. Nine hundred and fifty proteins were identified and annotated using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases; they are involved in a variety of metabolic and signalling pathways, including amino acid, lipid, and carbohydrate metabolism, and the PI3K-Akt signalling pathway. There were 296 differentially expressed proteins (DEPs), with 143 up-regulated and 153 down-regulated proteins. Three proteins involved in triglyceride and fatty acid syntheses and two proteins involved in autophagy were up-regulated, and six proteins involved in lipid catabolism were down-regulated. These results indicate that under short-term starvation, lipid droplets in the adipose tissue of grass carp may maintain their shape by promoting fat production and inhibiting lipolysis, and autophagy may be one of the main strategies for coping with short-term energy deprivation.

[A study on the relativity between La protein and the stability of HBV mRNA and the expression of HBV protein].

OBJECTIVE: To study the relativity between La protein and the stability of HBV mRNA and the expression of HBV protein. METHODS: Four specific siRNAs were obtained by transcription in vitro. After transfection with the siRNAs into HepG2.2.15 cells for 3 days, the inhibitive effects of La protein were analyzed by Western blot; the content changes of HBsAg, HBeAg and HBV-DNA were detected by ECL and RT-PCR. RESULTS: In comparison to normal cells, La protein was less in the cells. There was less La protein in the cells trans-infected with siRNAs. HBsAg, the HBeAg and HBV-DNA secreted by the cells transfected with siRNA were also less than that in the normal cells. CONCLUSION: There is a correlation between La protein and HBV mRNA and the expression of HBV protein.