👤 Haoyu Zu

Parkinson's disease (PD) is a prevalent neurodegenerative disorder predominantly affecting individuals over 60. Its motor symptoms stem from the deterioration of dopaminergic neurons within the substantia nigra. Despite aging being a significant risk factor, the specific mechanisms linking aging and PD pathology remain unclear. Leveraging advancements in single-cell genomics, this study utilizes single-nucleus multiome sequencing to capture transcriptomic and epigenetic profiles from 40,125 cells across the lifespan of the mouse substantia nigra. Our analysis pinpoints age-associated changes at a cell type-specific level, revealing a subset of genes that increasingly express with age and are enriched in PD-related pathways, notably in oligodendrocytes at late aging stages. Integration with five public PD single-cell RNA-seq data sets highlights 85 genes consistently differentially expressed with aging and PD. Key genes such as Show less

Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac hypertrophy. SMURF2 (SMAD-specific E3 ubiquitin ligase 2) is an important member of NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) family of HECT E3 ubiquitin ligases. In this study we investigated the regulatory role of SMURF2 in cardiac hypertrophy. Experiment models were established in mice by transverse aortic constriction (TAC) in vivo, as well as in neonatal rat cardiomyocytes (NRCMs) by treatment with angiotensin II (Ang II, 1 μM) in vitro. We showed that the expression levels of SMURF2 were significantly elevated in cardiac tissues from patients with cardiac hypertrophy and the two experiment models. In NRCMs, SMURF2 knockdown or treatment with a specific SMURF2 inhibitor heclin (8 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, evidenced by reduced mRNA levels of Anp, Bnp and β-Mhc as well as cell surface. Prophylactic or therapeutic administration of heclin (10 mg·kg Show less

ANGPTL3, 4 and 8 have been reported to be involved in the regulation of lipid and glucose metabolism. The aim of this study was to investigate the expression of ANGPTL3, 4, 8 in hypertensive patients with or without overweight/obesity, T2D, and hyperlipidemia, and the possible association between their expression and the status of the aforementioned comorbidities. Plasma levels of ANGPTL3, 4, and 8 in 87 hospitalized patients with hypertension were measured using ELISA kits. Associations between circulating ANGPTLs levels and the most common additional cardiovascular risk factors were assessed using multivariate linear regression analyses. Pearson's correlation analysis was used to examine the association between ANGPTLs and clinical parameters. In the context of hypertension, (1) although not statistically significant, circulating ANGPTL3 levels were higher in the overweight/obese group than in the normal weight group; (2) circulating levels of ANGPTL3 and ANGPTL8 were significantly lower in patients with T2D than in non-diabetic patients; (3) circulating ANGPTL3 levels were significantly higher in the hyperlipidemic group than in the non-hyperlipidemic group. ANGPTL3 was associated with T2D and hyperlipidemia status, whereas ANGPTL8 was independently associated with T2D status. In addition, circulating ANGPTL3 levels were positively correlated with TC, TG, LDL-C, HCY, and ANGPTL8, and circulating ANGPTL4 levels were positively correlated with UACR and BNP. Changes in circulating ANGPTL3 and ANGPTL8 levels have been observed in hypertensive patients with the most common additional cardiovascular risk factors, suggesting a role in the common comorbidities of hypertension and cardiovascular disease. Hypertensive patients with overweight/obesity or hyperlipidemia may benefit from therapies targeting ANGPTL3. Show less

Since the prognosis of patients with pancreatic cancer is very poor and there is a lack of treatment methods, this study is performed to investigate the function of PITX2 in pancreatic stellate cells (PSCs) in the progression of pancreatic cancer. Scientific hypotheses are proposed according to bioinformatics analysis and tissue microarray analysis. Stable knockdown of Show less

Primary tumor tissue is often analyzed to search for predictive biomarkers and DNA-guided personalized therapies, but there is an incomplete understanding of the discrepancies in the genomic profiles between primary tumors and metastases, such as liver and lung metastases. We performed in-depth targeted next-generation sequencing of 520 key cancer-associated genes for 47 matched primary and metastatic tumor samples which were retrospectively collected. A total of 699 mutations were detected in the 47 samples. The coincidence rate of primary tumors and metastases was 51.8% (n = 362), and compared to patients with liver metastases, patients with lung metastases had a significantly greater coincidence rate ( In this study, we demonstrate significant differences in the genomic landscapes of colorectal cancer patients based on the site of metastasis. Notably, we observe a larger genomic variation between primary tumors and liver metastasis compared to primary tumors and lung metastasis. These findings can be used for tailoring treatments based on the specific metastatic site. Show less

The quadrilateral reassortant IAV A/(H1N1) pdm09 is the pathogen responsible for the first influenza pandemic of the 21st century. The virus spread rapidly among hosts causing high mortality within human population. Efficient accumulation of virions is known to be important for the rapid transmission of virus. However, the mechanism by which A/(H1N1) pdm09 promotes its rapid replication has not been fully studied. Here, we found the NS1 of A/(H1N1) pdm09 mediated complete macroautophagy/autophagy, and then facilitated self-replication, which may be associated with the more rapid spread of this virus compared with H1N1 Show less

ERK1/2 are essential proteins mediating mitogen-activated protein kinase signaling downstream of RAS in pancreatic adenocarcinoma (PDAC). Our previous study reveals that ARF6 plays a positive regulatory role in ERK1/2 pathway in a feedback loop manner. A significant part of the literature on ARF6 has emphasized its oncogenic effect as an essential downstream molecule of ERK1/2, and no research has been done on the regulation mechanisms of the feedback loop between ARF6 and the ERK1/2 signaling pathway. In the present study, we explore the gene network downstream of Show less

The diameter of the abdominal aortic aneurysm (AAA) is the most commonly used parameter for the prediction of occurrence of AAA rupture. However, the most vulnerable region of the aortic wall may be different from the most dilated region of AAA under pressure. The present study is the first to use weighted gene coexpression network analysis (WGCNA) to detect the coexpressed genes that result in regional weakening of the aortic wall. The GSE165470 raw microarray dataset was used in the present study. Differentially expressed genes (DEGs) were filtered using the "limma" R package. DEGs were assessed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. WGCNA was used to construct the coexpression networks in the samples with regional weakening of the AAA wall and in the control group to detect the gene modules. The hub genes were defined in the significant functional modules, and a hub differentially expressed gene (hDEG) coexpression network was constructed with the highest confidence based on protein-protein interactions (PPIs). Molecular compound detection (MCODE) was used to identify crucial genes in the hDEG coexpression network. Crucial genes in the hDEG coexpression network were validated using the GSE7084 and GSE57691 microarray gene expression datasets. A total of 350 DEGs were identified, including 62 upregulated and 288 downregulated DEGs. The pathways were involved in immune responses, vascular smooth muscle contraction and cell-matrix adhesion of DEGs in the samples with regional weakening in AAA. Antiquewhite3 was the most significant module and was used to identify downregulated hDEGs based on the result of the most significant modules negatively related to the trait of weakened aneurysm walls. Seven crucial genes were identified and validated: ACTG2, CALD1, LMOD1, MYH11, MYL9, MYLK, and TPM2. These crucial genes were associated with the mechanisms of AAA progression. We identified crucial genes that may play a significant role in weakening of the AAA wall and may be potential targets for medical therapies and diagnostic biomarkers. Further studies are required to more comprehensively elucidate the functions of crucial genes in the pathogenesis of regional weakening in AAA. Show less

Salvianolic acid A (SalA), one of the most efficacious polyphenol compounds extracted from Radix Salvia miltiorrhiza (Danshen), has been shown to possess many potential pharmacological activities. This study aimed to investigate whether SalA has hepatoprotective effects against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore the mechanism underlying this process. SalA treatment significantly attenuated HFD-induced obesity and liver injury, and markedly decreased lipid accumulation in HFD-fed rat livers. Moreover, SalA treatment ameliorated HFD-induced hepatic inflammation and oxidative stress by decreasing hepatotoxic levels of cytokines, suppressing the overproduction of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) and preventing the decreased expression of superoxide dismutase (SOD). Importantly, SalA reversed the HFD- or palmitic acid (PA)-induced activation of the NLRP3 inflammasome, the nuclear translocation of ChREBP and the up-regulation of FAS, and these effects were accompanied by TXNIP down-regulation. However, TXNIP siRNA treatment partially abrogated the above-mentioned effects of SalA in PA-treated HepG2 cells. Together, our results demonstrated, for the first time, that SalA protects against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation, and these protective effects may partially due to regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways. Show less

To search for a new method of screening for molecular targets for androgen-dependent prostate cancer. We collected tissue samples and paired serum samples from 3 cases of androgen-dependent prostate cancer (ADPC) treated by surgical resection, and included another 3 samples of benign prostatic hyperplasia (BPH) tissue and normal human serum in the control group. The total proteins extracted were separated and transmembrane by two-dimensional gel electrophoresis, followed by hybridization with the sera of the patients with ADPC and those with hormone-independent prostate cancer (HIPC) as the primary antibodies. The differentially expressed proteins were compared by Western blot, analyzed by MALDI-TOF-MS mass spectrography, and verified by RT-PCR and Western blot following bioinformatic identification. This modified method exhibited a significantly better effect in displaying differentially expressed proteins, by which 12 differentially expressed protein spots were identified, including Beclin1, glutathione S-transferase P (GSTP1-1), ZBTB7, dihydrodiol dehydrogenase 2 (DDH), enolase (ENO1), glucose-dependent insulin-releasing peptide receptor (GIPR), Mn-superoxide dismutase (MnSOD), phosphoglycerate mutase 1 (PGAM1), amino-peptidyl-prolyl cistrons isomerase (PPIA), and phospholipid-PE-binding protein (PEBP). The mRNA and protein expressions of Beclin1 were significantly down-regulated in androgen-dependent prostate cancer tissues. This modified serum-guided immunoblotting technique has provided a new method for clarifying the molecular mechanisms of the occurrence and progression of HIPC, in which Beclin1-mediated autophagy may play a key role. Show less