Unraveling CCL20's role by regulating Th17 cell chemotaxis in experimental autoimmune prostatitis.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.

Development and evaluation of inactivated vaccines incorporating a novel Senecavirus A strain-based Immunogen and various adjuvants in mice.

Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection.

Neuroimmune modulation mediated by IL-6: A potential target for the treatment of ischemia-induced ventricular arrhythmias.

BACKGROUND: Neural remodeling in the left stellate ganglion (LSG), as mediated by neuroimmune reactions, promotes cardiac sympathetic nerve activity (SNA) and thus increases the incidence of ventricular arrhythmias (VAs). Interleukin-6 (IL-6) is an important factor of the neuroimmune interaction. OBJECTIVE: The present study explored the effects of IL-6 on LSG hyperactivity and the incidence of VAs. METHODS: Eighteen beagles were randomly allocated to a control group (saline with myocardial infarction [MI], n = 6), adeno-associated virus (AAV) group (AAV with MI, n = 6), and IL-6 group (overexpression of IL-6 via AAV vector with MI, n = 6). Ambulatory electrocardiography was performed before and 30 days after AAV microinjection into the LSG. LSG function and ventricular electrophysiology were assessed at 31 days after surgery, and a canine MI model was established. Samples of the LSG were collected for immunofluorescence staining and molecular biological evaluation. Blood samples and 24-hour Holter data were obtained from 24 patients with acute MI on the day after they underwent percutaneous coronary intervention to assess the correlation between IL-6 levels and SNA. RESULTS: IL-6 overexpression increased cardiac SNA and worsened postinfarction VAs. Furthermore, sustained IL-6 overexpression enhanced LSG function, promoted expression of nerve growth factor, c-fos, and fos B in the LSG, and activated the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway. Clinical sample analysis revealed a correlation between serum IL-6 levels and heart rate variability frequency domain index as well as T-wave alternans. CONCLUSION: IL-6 levels are correlated with cardiac SNA. Chronic overexpression of IL-6 mediates LSG neural remodeling through the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway, elevating the risk of VA after MI.

Chronic Expression of Interleukin-10 Transgene Modulates Cardiac Sympathetic Ganglion Resulting in Reduced Ventricular Arrhythmia.

The cardiac autonomic nervous system (CANS) is intimately connected to the regulation of electrophysiology and arrhythmogenesis in cardiac systems. This work aimed at investigating whether interleukin-10 (IL-10) could effectively modulate CANS and suppress ischemia-induced ventricular arrhythmia (VA) through chronically acting on the cardiac sympathetic ganglion (CSG). Using an adeno-associated virus (AAV), we achieved local chronic overproduction of IL-10 in the CSG, left stellate ganglion (LSG). As a result, in the IL-10 group, we observed a decreased number of tyrosine hydroxylase-positive (TH+) cells in the LSG. IL-10 markedly downregulated the nerve growth factor, synaptophysin, as well as growth-associated protein 43 expression. In vivo, results from ambulatory electrocardiography showed that IL-10 overexpression significantly inhibited the cardiac sympathetic nervous system activity and improved heart rate variability. Meanwhile, we observed decreased LSG function as well as prolonged ventricular effective refractory period and suppressed VA after myocardial infarction (MI) in the IL-10 group. In addition, IL-10 overexpression attenuated inflammation and decreased norepinephrine levels in the myocardium after acute MI. In conclusion, our data suggest that chronic IL-10 overexpression modulates cardiac sympathetic nerve remodeling and suppresses VA induced by MI. Neuromodulation through AAV-mediated IL-10 overexpression may have the characteristics of and advantages as a potential neuroimmunotherapy for preventing MI-induced VAs.

Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway.

Choline is a precursor of the major neurotransmitter acetylcholine and has been demonstrated beneficial in diverse models of cardiovascular disease. Here, we sought to verify that choline protects the heart from DOX-induced cardiotoxicity and the underlying mechanisms. The results showed that DOX treatment decreased left ventricular ejection fraction and fractional shortening and increased serum cardiac markers and myocardial fibrosis, which were alleviated by cotreatment with choline. DOX-induced cardiotoxicity was accompanied by increases in oxidative stress, inflammation, and apoptosis, which were rectified by choline cotreatment. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1), which are antioxidant markers, were lowered by DOX and upregulated by choline. Moreover, DOX significantly decreased serum acetylcholine levels and the high-frequency component of heart rate variability and increased serum norepinephrine levels and the low-frequency component; these effects were rescued by choline administration. Interestingly, the protective effects of choline could be partially reversed by administration of the muscarinic receptor antagonist atropine. This suggests that choline might be a promising adjunct therapeutic agent to alleviate DOX-induced cardiotoxicity.

The correlation between affected renal function and affected renal residual volume: A retrospective outcome of laparoscopic nephron-sparing partial nephrectomy with segmental renal artery blocking-up for localized renal tumors.

Laparoscopic nephron-sparing partial nephrectomy with segmental renal artery blocking (SRPN) has been widely used in the treatment of localized renal tumors. However, the impact of ischemia-reperfusion injury (IRI) during SRPN remains controversial. This study aims to evaluate the correlation between affected renal function and affected renal volume after SRPN for localized renal tumor treatment, explore the effect of IRI on renal function after SRPN.A total of 39 patients who underwent SRPN for localized renal tumor from June 2009 to April 2012 were reviewed. These patients were followed-up for 5 years. The preoperative affected renal glomerular filtration rate (aGFRpre), postoperative affected renal glomerular filtration rate (aGFRpost), preoperative affected renal volume (aVolpre), and postoperative affected renal volume (aVolpost) were collected during the follow-up period. The correlation between aGFRpost/aGFRpre and aVolpost/aVolpre was compared.A total of 33 patients were successfully followed up. After 3, 6, 12, 24, and 60 months, aGFRpost was 34.6 ±â€Š4.6, 34.7 ±â€Š4.8, 34.9 ±â€Š4.4, 35.1 ±â€Š4.4, and 35.2 ±â€Š4.2 mL/min. The correlation coefficients between aGFRpost/aGFRpre and aVolpost/aVolpre were 0.659 (P = .000), 0.667 (P = .000), 0.663 (P = .000), 0.629 (P = .000), and 0.604 (P = .000), respectively. The limitation of this study was the small cohort size.For the localized renal tumor, aGFRpost was associated with aVolpost, but was not associated with intraoperative factors, such as the time of clamping of the affected segmental renal artery. As a part of nephrons, the resected tumor tissue caused the lack of inherent nephrons, resulting in the loss of renal function. More nephrons should be maintained before resecting the tumor completely during SRPN.Trial registration: ChiCTR-RRC-17011418.

Effects on All-cause Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes by Comparing Insulin With Oral Hypoglycemic Agent Therapy: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: Retrospective, case-control studies and prospective randomized controlled trials (RCTs) on insulin treatment for diabetic patients yielded contradictory mortality and cardiovascular outcomes. We aimed to evaluate the effects of insulin versus oral hypoglycemic agents (OHAs) on all-cause mortality and cardiovascular outcomes in patients with type 2 diabetes (T2D). METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Chinese Technical Periodicals, and Wanfang Data, up to July 10, 2015, for RCTs on insulin and OHAs that assessed all-cause mortality and/or cardiovascular death as primary end points. We derived pooled risk ratios (RRs) as summary statistics. RESULTS: Three trials were included in which 7649 patients received insulin and 8322 received OHAs, with mean (SD) diabetes duration of 5.0 (6.2) and 4.4 (5.9) years, respectively. Insulin did not differ from OHAs in all-cause mortality (RR = 1.00; 95% CI, 0.93-1.07), cardiovascular death (RR = 1.00; 95% CI, 0.91-1.09), myocardial infarction (RR = 1.04; 95% CI, 0.93-1.16), angina (RR = 0.97; 95% CI, 0.88-1.06), sudden death (RR = 1.02; 95% CI, 0.66-1.56), or stroke (RR = 1.01; 95% CI, 0.88-1.15). Insulin reduced the risk of heart failure compared with OHAs (RR = 0.87; 95% CI, 0.75-0.99). In the subgroup of secondary prevention of cardiovascular diseases (CVDs) or very high risk of CVDs, insulin did not differ from OHAs in all-cause mortality (RR = 0.99; 95% CI, 0.92-1.07), cardiovascular death (RR = 0.99; 95% CI, 0.90-1.09), myocardial infarction (RR = 1.01; 95% CI, 0.88-1.15), heart failure (RR = 0.69; 95% CI, 0.34-1.40), or stroke (RR = 1.05; 95% CI, 0.90-1.21). IMPLICATIONS: Insulin did not provide a clear benefit over OHAs in all-cause mortality or cardiovascular outcomes in the patients with T2D. Insulin therapy has many shortcomings, including inconvenience (injection, strict blood glucose monitoring), hypoglycemia, and obvious weight gain. Thus, we conclude that no robust evidence supports the active use of insulin for this population at present.

Acarbose Monotherapy and Type 2 Diabetes Prevention in Eastern and Western Prediabetes: An Ethnicity-specific Meta-analysis.

PURPOSE: Acarbose is effective in delaying or preventing the progression of prediabetes to type 2 diabetes mellitus (T2DM). The aim of this study was to assess differences in the preventive effects of acarbose in Eastern and Western populations with prediabetes. METHODS: We performed a systematic search of databases and reference lists of clinical trials conducted through August 2013. Randomized controlled trials of acarbose alone, with a minimum intervention duration of 3 years and which provided data on T2DM incidence, were included for analysis. Analyses were conducted by using Review Manager version 5.1 software. FINDINGS: Eight randomized controlled trials with 2628 participants were included. Acarbose decreased the occurrence of T2DM (number needed to treat [NNT], 6.7). Compared with the control (placebo and/or lifestyle intervention), the incidence of T2DM was significantly lower in the Eastern group (NNT, 5.9) than in the Western group (NNT, 11.1) (P < 0.0001, I(2) = 94.7%). At the end of follow-up, reversal of prediabetes to normal glucose tolerance was more likely in the Eastern group (NNT, 4.3) than in the Western group (NNT, 25) (P = 0.004, I(2) = 92%). Among those remaining prediabetic, there was no significant difference between the subtotal estimates for the subgroups (P = 0.17, I(2) = 46.5%). There was no positive correlation between preventive effect and dose, and no difference in studies with varying follow-up durations within and across either ethnic group. IMPLICATIONS: The preventive effect of acarbose on the development of diabetes seems superior in Eastern populations with prediabetes compared with Western populations.