Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis

Qian Liu,Bishao Sun,Jiang Zhao,Qingqing Wang,Fan An,Xiaoyan Hu,Zhenxing Yang,Jie Xu,Mingjia Tan,Longkun Li 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

The Piezo1 channel is a mechanotransduction mediator, and Piezo1 abnormalities have been linked to several clinical disorders. However, the role of the Piezo1 channel in cystitis-associated bladder dysfunction has not been documented. The current study aimed to discover the functional role of this channel in regulating bladder activity during cyclophosphamide (CYP)-induced cystitis. One hundred four female rats were randomly assigned to the control, CYP-4h, CYP-48h and CYP-8d groups. CYP successfully induced acute or chronic cystitis in these rats. CYP treatment for 48h or 8d significantly increased Piezo1 channel expression in bladder interstitial Cajal-like cells (ICC-LCs), and the increase in CYP-8d rats was more prominent. In addition, 2.5 μM Grammostola spatulata mechanotoxin 4 (GsMTx4) significantly attenuated bladder hyperactivity in CYP-8d rats by inhibiting the Piezo1 channel in bladder ICCLCs. Furthermore, by using GsMTx4 and siRNA targeting the Piezo1 channel, we demonstrated that hypotonic stressinduced Piezo1 channel activation significantly triggered Ca2+ and Na+ influx into bladder ICC-LCs during CYPinduced chronic cystitis. In addition, the Piezo1 channel functionally interacted with the relatively activated reverse mode of Na+/Ca2+ exchanger 1 (NCX1) in bladder ICC-LCs from CYP-8d rats. In conclusion, we suggest that the functional role of the Piezo1 channel in CYP-induced chronic cystitis is based on its synergistic effects with NCX1, which can significantly enhance [Ca2+]i and result in Ca2+ overload in bladder ICC-LCs, indicating that the Piezo1 channel and NCX1 are potential novel therapeutic targets for chronic cystitis-associated bladder hyperactivity.

Prevalence of Intracranial Aneurysm in Patients with Aortopathy: A Systematic Review with Meta-Analyses

Xinyu Yu,Liangtao Xia,Qingqing Jiang,Yupeng Wei,Xiang Wei,Shiyi Cao 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.1

Background and Purpose Patients with aortic disease might have an increased risk of intracranial aneurysm (IA). We conducted this research to assess the prevalence of IA in patients with aortopathy, considering the impact of gender, age, and cardiovascular risk factors. Methods We searched PubMed and Scopus from inception to August 2019 for epidemiological studies reporting the prevalence of IA in patients with aortopathy. Random-effect meta-analyses were performed to calculate the overall prevalence, and the effect of risk factors on the prevalence was also evaluated. Anatomical location of IAs in patients suffered from distinct aortic disease was extracted and further analyzed. Results Thirteen cross-sectional studies involving 4,041 participants were included in this systematic review. We reported an estimated prevalence of 12% (95% confidence interval [CI], 9% to 14%) of IA in patients with aortopathy. The pooled prevalence of IA in patients with bicuspid aortic valve, coarctation of the aorta, aortic aneurysm, and aortic dissection was 8% (95% CI, 6% to 10%), 10% (95% CI, 7% to 14%), 12% (95% CI, 9% to 15%), and 23% (95% CI, 12% to 34%), respectively. Gender (female) and smoking are risk factors related to an increased risk of IA. The anatomical distribution of IAs was heterogeneously between participants with different aortic disease. Conclusions According to current epidemiological evidence, the prevalence of IA in patients with aortic disease is quadrupled compared to that in the general population, which suggests that an early IA screening should be considered among patients with aortic disease for timely diagnosis and treatment of IA.

Bayesian-theory-based Fast CU Size and Mode Decision Algorithm for 3D-HEVC Depth Video Inter-coding

( Fen Chen ),( Sheng Liu ),( Zongju Peng ),( Qingqing Hu ),( Gangyi Jiang ),( Mei Yu ) 한국인터넷정보학회 2018 KSII Transactions on Internet and Information Syst Vol.12 No.4

Multi-view video plus depth (MVD) is a mainstream format of 3D scene representation in free viewpoint video systems. The advanced 3D extension of the high efficiency video coding (3D-HEVC) standard introduces new prediction tools to improve the coding performance of depth video. However, the depth video in 3D-HEVC is time consuming. To reduce the complexity of the depth video inter coding, we propose a fast coding unit (CU) size and mode decision algorithm. First, an off-line trained Bayesian model is built which the feature vector contains the depth levels of the corresponding spatial, temporal, and inter-component (texture-depth) neighboring largest CUs (LCUs). Then, the model is used to predict the depth level of the current LCU, and terminate the CU recursive splitting process. Finally, the CU mode search process is early terminated by making use of the mode correlation of spatial, inter-component (texture-depth), and inter-view neighboring CUs. Compared to the 3D-HEVC reference software HTM-10.0, the proposed algorithm reduces the encoding time of depth video and the total encoding time by 65.03% and 41.04% on average, respectively, with negligible quality degradation of the synthesized virtual view.

Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice

Qian Liu,Zhou Long,Xingyou Dong,Teng Zhang,Jiang Zhao,Bishao Sun,Jingzhen Zhu,Jia Li,Qingqing Wang,Zhenxing Yang,Xiaoyan Hu,Longkun Li 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively. Cyclophosphamide (CYP)-induced cystitis models were successfully established in these mice. CYP treatment significantly enhanced HCN channel protein expression and Ih density and significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH) and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca2+]i in CYP-treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased the effects of CCH and FSK on bladder ICC-LC [Ca2+]i in both naive and CYP-treated mice. CYP treatment significantly potentiated the spontaneous contractions and CCH (0.001–10 μM)-induced phasic contractions of detrusor strips, and HCN1 channel deletion significantly abated such effects. Finally, we demonstrated that the development of CYP-induced bladder overactivity was reversed in HCN1 / mice. Taken together, our results suggest that CYP-induced enhancements of HCN1 channel expression and function in bladder ICC-LCs are essential for cystitis-associated bladder hyperactivity development, indicating that the HCN1 channel may be a novel therapeutic target for managing bladder hyperactivity.

Loss of KDM5B ameliorates pathological cardiac fibrosis and dysfunction by epigenetically enhancing ATF3 expression

Wang Bo,Tan Yong,Zhang Yunkai,Zhang Sheng,Duan Xuewen,Jiang Yuyu,Li Tong,Zhou Qingqing,Liu Xingguang,Zhan Zhenzhen 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Excessive cardiac fibrosis is central to adverse cardiac remodeling and dysfunction leading to heart failure in many cardiac diseases. Histone methylation plays a crucial role in various pathophysiological events. However, the role of histone methylation modification enzymes in pathological cardiac fibrosis needs to be fully elucidated. Here, we identified lysine demethylase 5B (KDM5B), a histone H3K4me2/me3 demethylase, as a key epigenetic mediator of pathological cardiac fibrosis. KDM5B expression was upregulated in cardiac fibroblasts and myocardial tissues in response to pathological stress. KDM5B deficiency markedly ameliorated cardiac fibrosis, improved cardiac function, and prevented adverse cardiac remodeling following myocardial infarction (MI) or pressure overload. KDM5B knockout or inhibitor treatment constrained the transition of cardiac fibroblasts to profibrogenic myofibroblasts and suppressed fibrotic responses. KDM5B deficiency also facilitated the transformation of cardiac fibroblasts to endothelial-like cells and promoted angiogenesis in response to myocardial injury. Mechanistically, KDM5B bound to the promoter of activating transcription factor 3 (Atf3), an antifibrotic regulator of cardiac fibrosis, and inhibited ATF3 expression by demethylating the activated H3K4me2/3 modification, leading to the enhanced activation of TGF-β signaling and excessive expression of profibrotic genes. Our study indicates that KDM5B drives pathological cardiac fibrosis and represents a candidate target for intervention in cardiac dysfunction and heart failure.