Study on pyroptosis-related genes Casp8, Gsdmd and Trem2 in mice with cerebral infarction.

Objective: Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction. Methods and results: A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively. Differentially expressed pyroptosis-related genes (including Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6 and Trem2) were obtained through intersection of DEGs and genes from pyroptosis Gene Ontology Term (GO:0070269), and they were up-regulated in the brain tissues of MCAO mice in GSE137482. In addition, Casp8, Gsdmd, and Trem2 were verified to be significantly up-regulated in MCAO mice in GSE93376. The evaluation of neurologic function and triphenyltetrazolium chloride staining showed that the MCAO mouse models were successfully constructed. Meanwhile, the expressions of TNF-α, pyroptosis-related proteins, Casp8, Gsdmd and Trem2 in MCAO mice were significantly up-regulated. We selected Trem2 for subsequent functional analysis. OGD treatment of BV2 cell in vitro significantly upregulated the expressions of Trem2. Subsequent downregulation of Trem2 expression in OGD-BV2 cells further increased the level of pyroptosis. Therefore, Trem2 is a protective factor regulating pyroptosis, thus influencing the progression of cerebral infarction. Conclusions: Casp8, Gsdmd and Trem2 can regulate pyroptosis, thus affecting cerebral infarction.

Therapeutic effects of Buyang Huanwu Tang combined with RT-PA intravenous thrombolysis on stroke of Qi deficiency and blood stasis type and its impact on Keap1-Nrf2/ARE pathway antioxidant stress.

This study investigated the impact of combining traditional Chinese medicine, Buyang Huanwu Tang, with intravenous thrombolysis using alteplase (rt-PA) in treating ischemic stroke patients with qi deficiency and blood stasis. A single-center clinical randomized trial involved 117 ischemic stroke patients treated with rt-PA in the neurology department from January 2019 to December 2021. Patients were randomly divided into two groups: the control group (58 patients) received rt-PA alone, while the combined group (59 patients) received rt-PA along with Buyang Huanwu Tang. Neurological deficit scores (NIHSS) were assessed before and after treatment, along with hemorheological indicators, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and Keap1-Nrf2/ARE pathway oxidative stress indicators (Keap1, Nrf2, ARE, and NQO1 proteins). Before treatment, there were no significant differences between the groups. After treatment, the combination group exhibited lower NIHSS scores at 4, 8, and 12 weeks, indicating significant improvement compared to the control group. Additionally, the combination group demonstrated reduced plasma viscosity, low and high shear viscosity, and improved red blood cell aggregation compared to the control group after 8 weeks of treatment. Furthermore, the combination group showed elevated MMP-9 levels and reduced VEGF levels, suggesting favorable outcomes. Regarding the Keap1-Nrf2/ARE pathway, Nrf2 and NQO1 protein expression levels were higher in the combination group after 8 weeks of treatment. Clinical efficacy assessment revealed that the combined treatment group had a significantly better overall treatment response. In conclusion, combining Buyang Huanwu Tang with rt-PA intravenous thrombolysis effectively mitigated oxidative stress damage in the Keap1-Nrf2/ARE pathway among ischemic stroke patients with qi deficiency and blood stasis. This approach promoted neurological function recovery and improved overall treatment outcomes.

Associations between low-carbohydrate and low-fat diets and hepatic steatosis.

OBJECTIVE: This study assessed the cross-sectional associations of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) with hepatic steatosis in the National Health and Nutrition Examination Survey. METHODS: Diet was measured using the 24-hour recalls. Hepatic steatosis was defined by vibration-controlled transient elastography. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Substitution analysis was performed using the leave-one-out model. RESULTS: Participants with higher adherence scores (comparing extreme tertiles) for an overall (OR = 0.76, 95% CI: 0.61-0.96, ptrend  = 0.049) or a healthful LCD (OR = 0.61, 95% CI: 0.43-0.87, ptrend < 0.001) exhibited lower odds of steatosis. Replacing 5% of the energy from carbohydrates with total fat and protein (OR = 0.91, 95% CI: 0.83-0.99) or unsaturated fat and plant protein (OR = 0.89, 95% CI: 0.84-0.94) was associated with lower steatosis prevalence. High overall (OR = 1.65, 95% CI: 1.13-2.40, ptrend  = 0.006) or unhealthful (OR = 1.41, 95% CI: 1.10-1.80, ptrend < 0.001) LFD scores were associated with increased likelihood of steatosis. CONCLUSIONS: These findings suggest that the associations between LCDs and LFDs and steatosis may depend on the quality and food sources of the macronutrients.

Association of Multiple Dopamine D3 Receptor Gene 3'UTR Polymorphisms with Susceptibility to Parkinson's Disease and Clinical Efficacy of Piribedil Therapy.

Objective: To investigate the correlation between the Dopamine D3 receptor (DRD3) 3'untranslated region (3'UTR) gene polymorphism and susceptibility to Parkinson's disease (PD) and the clinical effect of the DRD2 and DRD3 agonist piribedil treatment. Methods: Sanger sequencing was used to analyze the single nucleotide polymorphisms (SNPs) within the 3'UTR rs76126170, rs9868039, rs9817063, and rs3732790 loci of the DRD3 gene in 284 PD patients and 284 controls. PD patients were treated with piribedil sustained-release tablets (50 mg) combined with levodopa and benserazide hydrochloride tablets, three times daily (patients with first-diagnosed PD were only administrated with piribedil sustained-release tablets) for 3 months. The Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr disease stage were evaluated at baseline and after 3 months of treatment. Results: The T allele carriers of the DRD3 gene rs76126170 locus were more susceptible to PD than the C allele carriers (odds ratio [OR] = 3.44, 95% confidence interval [CI]: 2.46-4.80, p < 0.01). Carriers of the rs9868039 A allele had a decreased risk of PD compared to those with G allele (OR = 0.67, 95% CI: 0.53-0.86, p < 0.01). C allele carriers at rs9817063 were less likely to develop PD than those with T allele (OR = 0.74, 95% CI: 0.58-0.94, p = 0.02). No significant correlation was observed between the alleles or genotypes of the rs3732790 locus and PD susceptibility (p > 0.05). The various genotypes of the DRD3 gene loci rs76126170, rs9868039, and rs9817063 in PD patients were associated with significant differences with regard to reduction of UPDRS scores and Hoehn and Yahr stage after 3 months of treatment (p < 0.05). Conclusion: The alleles and genotypes of the DRD3 gene 3' UTR SNP loci rs76126170, rs9868039, and rs9817063 are associated with PD susceptibility and the clinical efficacy of piribedil treatment.

LncRNA STARD13-AS Expression in Gastric Cancer and its Significance.

BACKGROUND: The aim of the study is to investigate lncRNA STARD13-AS's expression and clinical characteristics in the cancer tissues of gastric cancer (GC) patients. METHODS: Microarray assessment will be used to analyze GC and non-tumor tissues. The lncRNA STARD13-AS expression in 82 GC and non-tumor tissues were measured by RT-qPCR and ISH assay. The differential expression of lncRNA STARD13-AS between the two groups and the relationship with clinical characteristics and prognosis were analyzed statistically. RESULTS: By microarray assessment, lncRNA STARD13-AS was significantly down-regulated in tumor tissues. Compared with non-tumor tissues, using both RT-qPCR and ISH assay, STARD13-AS expression was significantly depressed in GC tissues (p < 0.01, respectively) and was closely correlated with tumor stage and histological grade (p < 0.05, respectively), but was not correlated with gender, age, tumor size, tumor location or lymph node metastasis. The 5-year overall survival and progression free survival rates of the low lncRNA STARD13-AS expression group were significantly down-regulated compared with those of the high lncRNA STARD13-AS expression group (p < 0.001, respectively). CONCLUSIONS: The expression of lncRNA STARD-AS is depressed in gastric cancer tissues; the expression of lnc-RNA STARD-AS is correlated to tumor stage and degree of tumor differentiation, and may be a new molecular marker for the diagnosis, treatment, and prognosis in GC.

[Protective effect of curcumin on dopamine neurons in Parkinson's disease and its mechanism].

OBJECTIVE: To investigate the effect of curcumin on dopamine neurons in Parkinson's disease (PD) and its mechanism. METHODS: SH-SY5Y human neuroblastoma cells were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish the PD cell model. The model cells were treated with curcumin and/or autophagy inhibitor 3-MA. After 48 h of drug treatment, the number of surviving dopamine neurons was detected by tyrosine hydroxylase immunofluorescence method. Western blotting was used to detect protein expression of α-Synuclein (α-Syn), transcription factor EB (TFEB) and autophagy-related proteins lysosome-associated membrane protein 2A (LAMP2A) and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ); RT-PCR was used to detect mRNA expression of α-Syn. RESULTS: Compared with MPTP model group, curcumin increased the number of surviving dopamine neurons(P<0.01), decreased both protein expression and mRNA expression of α-Syn (all P<0.01), and increased protein expression of TFEB, LAMP2A and LC3-Ⅱ (all P<0.01). When curcumin and 3-MA were given concurrently, the number of surviving dopamine neurons, protein expression of TFEB, LAMP2A and LC3-Ⅱ increased (P<0.05 or P<0.01), and both protein expression and mRNA expression of α-Syn decreased (P<0.05 or P<0.01) compared with MPTP model group; but the number of surviving dopamine neurons and protein expression of LAMP2A and LC3-Ⅱ decreased compared with curcumin group (all P<0.05). CONCLUSIONS: Curcumin exerts protective effect on dopamine neurons in PD, which may be associated with enhancing autophagy and promoting the clearance of α-Syn.

Long noncoding RNA eosinophil granule ontogeny transcript inhibits cell proliferation and migration and promotes cell apoptosis in human glioma.

Glioma is the most common primary brain tumor and represents one of the most aggressive and lethal types of human cancer. Recent advances have implicated long noncoding RNAs (lncRNAs) as crucial mediators of cancer development and progression. The present study aimed to investigate the role of a newly-discovered lncRNA, termed eosinophil granule ontogeny transcript (EGOT), in the aggressive abilities of cells in human glioma. It was initially found that the relative transcription level of EGOT in glioma cancerous tissues was significantly lower than that in adjacent non-cancerous tissues. EGOT was differentially expressed in a series of glioma cell lines, with its lowest level in high aggressive U251 and U87 cells. When EGOT was overexpressed by an expression plasmid, cell viability was significantly inhibited in U251 and U87 cells. Furthermore, with EGOT overexpression, the cell cycle was arrested at G0/G1 phase and consequently, cell apoptosis was significantly promoted along with the activities of caspase-3 and caspase-9. The migration abilities of EGOT-overexpressed cells were inhibited by 71.4% in U251 cells and by 69.5% in U87 cells. These data suggest that overexpression of EGOT inhibits cell proliferation and migration, and promotes cell apoptosis in glioma. Therefore, EGOT has potent anticancer activity and may function as a tumor suppressor in human glioma.