Jinjian Yang

HMGB1 Is Involved in the Protective Effect of the PPARα Agonist Fenofibrate against Cardiac Hypertrophy

High mobility group box 1 (HMGB1) is a ubiquitous nuclear DNA-binding protein whose function is dependent on its cellular location. Extracellular HMGB1 is regarded as a delayed mediator of proinflammatory cytokines for initiating and amplifying inflammatory responses, whereas nuclear HMGB1 has been found to prevent cardiac hypertrophy and heart failure. Because fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, has shown both protective effects against cardiac hypertrophy and inhibitory effects against inflammation, the potential modulation of HMGB1 expression and secretion by fenofibrate is of great interest. We herein provide evidence that fenofibrate modulates basal and LPS-stimulated HMGB1 expression and localization in addition to secretion of HMGB1 in cardiomyocytes. In addition, administration of fenofibrate to mice prevented the development of cardiac hypertrophy induced by thoracic transverse aortic constriction (TAC) while increasing levels of nuclear HMGB1. Altogether, these data suggest that fenofibrate may inhibit the development of cardiac hypertrophy by regulating HMGB1 expression, which provides a new potential strategy to treat cardiac hypertrophy.

Restless legs syndrome and hypertension in Chinese pregnant women

Hypertension is a common complication of pregnancy, and studies show that pregnant women are more likely to suffer from restless legs syndrome (RLS). Pregnant women with hypertension and RLS often experience disrupted sleep patterns because of activation of the nervous system. The present study aimed to clarify the relationship between hypertension and RLS in pregnant women, and their impact on sleep. We enrolled 3,781 pregnant women who were admitted at our hospital for delivery between May 2011 and May 2014. The face-to-face questionnaire used to gather data included the International RLS Study Group criteria for diagnosis, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and hypertension diagnosis. Depending on the time of occurrence of hypertension, it was divided into two different types: pregnancy-induced hypertension and chronic hypertension in pregnancy. Out of 3,781 patients, 453 fulfilled the diagnostic criteria for RLS and 486 met the diagnostic criteria for hypertension. Among patients with RLS, prophylactic iron supplementation was less frequently taken during pregnancy. Pregnancy-induced hypertension, rather than chronic hypertension in pregnancy, was found to be more frequent in patients with RLS; pregnant women with RLS had higher PSQI and ESS scores than pregnant controls. In our study, RLS was frequent in pregnant women, especially in those without prophylactic iron supplementation. Patients with RLS described more serious sleep disruption and excessive daytime sleepiness (EDS). In addition, pregnancy-induced hypertension was more common in patients with RLS.

Adjuvant therapy for locally advanced renal cell carcinoma: A meta-analysis and systematic review

OBJECTIVES Many adjuvant therapies have been widely used in an attempt to reduce the local recurrence or distant metastasis of locally advanced renal cell carcinoma (RCC) after surgical resection. However, the benefits of adjuvant therapy remain controversial. Thus, we performed this study to analyze the role and safety of adjuvant therapy in renal cancer setting. METHODS AND METHODS We comprehensively searched PubMed, EMBASE, Web of Science, and the Cochrane Library for published randomized controlled trials comparing adjuvant therapy (chemotherapy, vaccine therapy, immune therapy, and targeted therapy) versus no active treatment after surgery among patients with locoregional RCC. Outcomes of interest were disease-free survival, overall survival, and severe toxicities. Different kinds of adjuvant therapy were evaluated separately. RESULTS Twelve studies (5,936 patients) were included in the present analysis. Adjuvant therapy did not contribute to overall survival (HR = 1.04; 95% CI: 0.95-1.15; P = 0.395; I2 = 0%) or disease-free survival (HR = 1.00; 95% CI: 0.92-1.08; P = 0.971; I2 = 35%) when compared to placebo or observation. No survival benefit was observed according to subgroup analyses (targeted therapy, vaccine therapy, and immune therapy). Moreover, adjuvant therapy increased obviously the risk of toxicities. CONCLUSIONS The addition of adjuvant therapy provided no survival benefit but increased the rates of adverse events for locally advanced RCC patients.

Involvement of interstitial cells of Cajal in bladder dysfunction in mice with experimental autoimmune encephalomyelitis

BackgroundBladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear.ObjectivesTo investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis.Materials and methodsThe EAE model was induced by a previously established method, and bladder functions in mice were evaluated. Bladders were harvested for the analysis of ICCs and the genes associated with bladder mechanosensation including pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and western blotting. The stem cell factor cytokine (SCF) was intraperitoneally injected at the beginning of EAE onset.ResultsEAE mice developed profound bladder dysfunction characterized by significant urine retention, increased micturition and decreased urine output per micturition. EAE induced a significant decrease in c-Kit expression and ICCs number. EAE also induced a significant increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of these pathological changes.ConclusionsICCs and stem cell factor play an important role in EAE-induced bladder dysfunction, which may be used as therapeutic options in treating patients with multiple sclerosis-related bladder dysfunction.

Effects of PGE2 EP3/EP4 receptors on bladder dysfunction in mice with experimental autoimmune encephalomyelitis

To investigate the expression of four subtypes of PGE2 E-prostanoid (EP) receptors (EP1-EP4) and the effects of EP3/EP4 on bladder dysfunction in a new neurogenic bladder model induced by experimental autoimmune encephalomyelitis (EAE), the mouse model of EAE was induced using a previously established method, and bladder function in mice with different defined levels of neurological impairment was then examined, including micturition frequencies and voiding weight. Bladders were then harvested for analysis of EP receptor expression by Western blot. Activities of agonists/antagonists of EP3 and EP4 receptors as well as PGE2 were also evaluated at different stages of EAE. The results showed that EAE mice developed profound bladder dysfunction characterized by significantly increased micturition and significantly decreased urine output per micturition. EAE-induced upregulation of EP3 and EP4 receptors in the bladder was accompanied by bladder dysfunction. However, EAE had no significant effect on EP1 and EP2 receptors. Moreover, PGE2 and agonists/antagonists of EP3 and EP4 receptors significantly affected bladder dysfunction in EAE mice. Thus, we believe that EAE mice are useful for investigations of the neurogenic bladder. In addition, EP3 and EP4 receptors play a role in EAE-induced bladder dysfunction, providing us with a new target for the treatment of neurogenic bladders.

Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma

BACKGROUND Acetyl-CoA synthetase 2 (ACSS2) is highly expressed in various cancers, whereas ACSS2 expression and function in renal cell carcinoma (RCC) are unknown. METHODS We investigated ACSS2 expression in 198 human RCC tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. Overexpression and knockdown of ACSS2 were used to investigate the proliferation, migration and invasion of human RCC 786-O, 769-P, and ACHN cell lines. RESULTS High-ACSS2 expression was associated with advanced T stage (P = 0.008), advanced tumor-node-metastasis stage (P = 0.015) and high University of California, Los Angeles, Integrated Staging System score category (P = 0.009). Multivariate analysis identified high-ACSS2 expression as a poor prognostic factor for recurrence-free survival (hazard ratio [HR] = 1.83, P = 0.038) and overall survival (HR = 1.60, P = 0.043). Cell-based functional assays showed that ACSS2 knockdown inhibited RCC cell growth, migration, and invasion, whereas overexpression of ACSS2 enhanced these effects. ACSS2 silencing inhibited PI3K/AKT signaling pathway. CONCLUSION ACSS2 may increase tumor progression and aggressive behavior and be an independent prognostic factor in RCC.

Single-plane retroperitoneoscopic adrenalectomy: a new operative procedure for benign adrenal disease

To evaluate the therapeutic effect of single-plane retroperitoneoscopic adrenalectomy. From February 2014 to March 2017, 251 patients underwent single-plane retroperitoneoscopic adrenalectomy, and their operative outcomes were compared with those of 98 patients who underwent anatomical three-plane retroperitoneoscopic adrenalectomy. Among 35 patients with a body mass index (BMI) of ≥30 kg/m2, their operative outcomes were compared between two operative procedures. The demographic data and perioperative outcomes of the patients were statistically analysed. The single-plane and three-plane groups were comparable in terms of estimated blood loss, time to oral intake, hospital stay, and incidence of complications among patients with similar baseline demographics. The single-plane group had a significantly shorter operation time (46.9 ± 5.8 vs 54.8 ± 7.0 mins, P < 0.0001) and lower analgesia requirement (56/251 vs 33/98, p = 0.03). For obese patients with a BMI of ≥30 kg/m2, single-plane adrenalectomy was also associated with a significantly shorter operation time(48.1 ± 6.2 vs 64.1 ± 5.1 mins, p < 0.0001). Single-plane retroperitoneoscopic adrenalectomy is feasible, safe, and effective in the treatment of adrenal masses <5 cm in size and provides a shorter operation time and better pain control than anatomical retroperitoneal adrenalectomy, especially in obese patients.

Down-regulation of miR-210-3p encourages chemotherapy resistance of renal cell carcinoma via modulating ABCC1

BackgroundATP-binding cassette transporter super-family including ABCC1 and MDR-1 were involved in multi-drug resistance (MDR) of renal cell carcinoma (RCC) patients. Several miRNAs were confirmed to promote the MDR and the survival of tumor cells.MethodsThe RCC cell lines Caki-2 with vinblastine-resistant (Caki-2/VBL) or doxorubicin-resistant (Caki-2/DOX) were constructed, respectively. The expressions of miR-210-3p, ABCC1 and MDR-1 protein were determined by qRT-PCR and Western blot assays. The viability of RCC cells was assessed by MTT assay. The regulatory relationship between miR-210-3p and ABCC1 was analyzed by Dual Luciferase assay. The effect of miR-210-3p in vivo was investigated with a tumor xenograft model in mice.ResultsMiR-210-3p expression was observed to significantly decrease in Caki-2/VBL and Caki-2/DOX cells. Meanwhile, ABCC1 and MDR-1 were significantly increased in Caki-2/VBL and Caki-2/DOX cells. ABCC1 was a novel target of miR-210-3p and negatively regulated by miR-210-3p. And miR-210-3p improved drug-sensitivity of RCC cells. Down-regulation of ABCC1 could reverse the effect of miR-210-3p knockdown on the drug-resistance and the level of MDR-1 in drug-sensitive RCC cells.ConclusionWe confirmed that down-regulation of miR-210-3p increased ABCC1 expression, thereby enhancing the MRP-1-mediated multidrug resistance of RCC cells.

High-mobility group box 1 is involved in the development of benign prostatic hyperplasia with chronic prostatic inflammation

Abstract Objective. The aims of this study were to explore the role of high-mobility group box 1 (HMGB1) in benign prostatic hyperplasia (BPH) and to perform a preliminary investigation of the mechanisms underlying BPH. Materials and methods. HMGB1 expression in 160 BPH cases was analyzed using immunohistochemistry. HMGB1 expression in primary prostate epithelial cells and the concentration of HMGB1 in the surrounding culture medium were detected by Western blotting and enzyme-linked immunosorbent assay, respectively. Cell proliferation was evaluated by the carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Student’s t test or a one- or two-way analysis of variance test, followed by Bonferroni post hoc analysis, were used to test differences between groups and time-course data. Results. HMGB1 expression was higher in BPH with prostatitis than in BPH alone and was positively correlated with prostate volume in BPH patients with prostatitis, but not in BPH patients without prostatitis. HMGB1 expression in primary prostate epithelial cells as well as its release into the extracellular environment increased when the cells were treated with the proinflammatory molecule lipopolysaccharide (LPS). In addition, HMGB1 overexpression promoted the proliferation of primary prostate epithelial cells under LPS stimulation, and this could be inhibited by the HMGB1 antagonist boxA. Conclusions. These findings provide novel insights into the pathogenic role of HMGB1 in BPH with prostatitis, and suggest that HMGB1 is a potential biomarker and therapeutic target for BPH.