The neutrophil percentage-to-albumin ratio is an independent risk factor for poor prognosis in peritoneal dialysis patients.

AIM: This study aimed to investigate the predictive ability of the neutrophil percentage-to-albumin Ratio (NPAR) concerning all-cause mortality and cardio-cerebrovascular mortality in patients undergoing peritoneal dialysis (PD). METHODS: We included a total of 807 PD patients from the Peritoneal Dialysis Center of the Second Affiliated Hospital of Soochow University between January 2009 and December 2019 in this study. Patients were categorized into three groups based on their baseline NPAR. The Kaplan-Meier method, multivariate Cox proportional hazard model, and Fine-Gray competing risk model were employed to examine the relationship between NPAR level and all-cause mortality and cardio-cerebrovascular mortality among PD patients. Furthermore, the ROC curve and calibration plots were utilized to compare the performance between NPAR and other conventional indicators. RESULTS: The mean follow-up period was 38.2 months. A total of 243 (30.1%) patients passed away, with 128 (52.7%) succumbing to cardio-cerebrovascular diseases. The mortality rates of the Middle and High NPAR groups were significantly greater than that of the Low NPAR group (p < 0.001), and NPAR was independently associated with all-cause mortality and cardio-cerebrovascular mortality. Receiver Operating Characteristic (ROC) analysis indicated that the Area Under the Curve (AUC) of NPAR (0.714) was significantly superior to those of C-reactive protein (CRP) (0.597), neutrophil to lymphocyte ratio (NLR) (0.589), C-reactive protein to albumin ratio (CAR) (0.698) and platelet to lymphocyte ratio (PLR) (0.533). CONCLUSION: NPAR served as an independent predictive marker for all-cause mortality and cardio-cerebrovascular mortality in PD patients. Moreover, NPAR demonstrated superior predictive potential compared to CRP, CAR, NLR, and PLR.

Apolipoprotein B and interleukin 1 receptor antagonist: reversing the risk of coronary heart disease.

Aims: Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms. Methods: Genetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CVDs and cardiometabolic risk factors were obtained from international genetic consortia. Inverse-variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches. Results: Genetically determined IL-1Ra level was associated with increased risk of coronary heart disease (CHD; OR, 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed. Conclusion: Apolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats.

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

Wnt/PCP pathway regulates the migration and neural differentiation of mesenchymal stem cells in vitro.

INTRODUCTION: Mesenchymal stem cells (MSCs) are an excellent donor graft source due to their potential for self-renewal and multidirectional differentiation. However, the potential mechanisms involved in MSC homing and neural differentiation are still unclear. The purpose of this study was to explore the effects of a chemokine, SDF-1a, and Wnt3a ligand on rat MSCs' migration and b-mercaptoethanol (BME)-induced neural differentiation of MSCs. MATERIALS AND METHODS: MSCs were isolated from rat bone marrow and cultured in vitro to passage 3. Scratch tests and transwell assays were used to estimate the effects of SDF-1a (25 ng/mL) and Wnt3a (10 ng/mL) on the migration of MSCs. The expression of Wnt/PCP pathway proteins RhoA, c-Jun, ATF2, and Wnt3a were assessed by Western blot. The 5 mM BME-induced neural differentiation of MSCs was determined by immunofluorescence to detect neuron- and astrocyte-specific markers such as nestin, GFAP, and Olig2. RESULTS: Wnt3a promoted the migration ability of MSCs and regulated the expression of RhoA, c-Jun, and ATF2 proteins. MSCs could differentiate into neural stem cells and astrocytes. Wnt3a enhanced BME induced neurogenesis in MSCs by increasing the protein expression of RhoA, c-Jun, and Wnt3a. CONCLUSIONS: The present study demonstrated that the Wnt/PCP pathway promotes migration and neural differentiation of rat MSC.

Mesenchymal Stem Cells: A Potential Therapeutic Strategy for Neurodegenerative Diseases.

Neurodegenerative disease is a kind of chronic, progressive nervous system disease characterized by neuron degeneration or apoptosis. Current treatments cannot prevent the development of the disease. Possible alternative treatments include cell therapy, especially with the use of mesenchymal stem cells (MSCs). MSCs are pluripotent stem cells with capacities for self-renewal and multidirectional differentiation. MSCs may serve as a reliable source of neural cells for potential cell replacement therapy or regenerative medicine treatment. Here, we summarized the therapeutic mechanisms of MSCs and how they can contribute to the development of treatments for neurodegenerative diseases.

Dimethyloxalyl Glycine Regulates the HIF-1 Signaling Pathway in Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal and multidirectional differentiation capabilities. Dimethyloxalyl glycine (DMOG) mobilizes MSCs, and the hypoxia inducible factor-1 (HIF-1) signaling pathway plays an important role in MSC mobilization. We aimed to investigate the effect of DMOG on the HIF-1 pathway in MSCs. Rats were treated with DMOG, and the numbers of peripheral blood MSCs (PB-MSCs) and bone marrow MSCs (BM-MSCs) were detected by the Colony-forming unit fibroblastic (CFU-F) method. The growth curve, cell cycle and migration ability of PB-MSCs and BM-MSCs were detected by CCK-8, Flow cytometry and Transwell assays. Western blotting and real-time qPCR were used to detect the expression of the HIF-1 pathway. The number of bone marrow microvessels was detected by immunohistochemistry. DMOG significantly increased the numbers of PB-MSCs and BM-MSCs (P < 0.05). Further, the MSCs in peripheral blood and bone marrow still had the ability to proliferate and migrate after mobilization by DMOG. The expression levels of HIF-1α, stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in MSCs were significantly regulated by DMOG (P < 0.05). The number of bone marrow microvessels decreased after the VEGF/VEGFR signaling pathway was blocked by SU5416 (P < 0.05). Therefore, these findings demonstrated that DMOG regulates the HIF-1α signaling pathway and promotes biological effects in MSCs.