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1Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1显示文摘Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.Na Kong Xiaying Chen Jiao Feng Ting Duan Shuiping Liu Xueni Sun Peng Chen Ting Pan Lili Yan Ting Jin Yu Xiang Quan Gao Chengyong Wen Weirui Ma Wencheng Liu Mingming Zhang Zuyi Yang Wengang Wang Ruonan Zhang Bi Chen Tian Xie Xinbing Sui Wei Tao 2021Acta Pharmaceutica Sinica B2021,11,12:23
2Effect of High Suspension and Low Incision Surgery Based on Traditional Ligation of Chinese Medicine in Treatment of Mixed Haemorrhoids:A Multi-centre,Randomized,Single-Blind,Non-inferiority Clinical Trial显示文摘Objective:To observe the clinical effect of high suspension and low incision(HSLI)surgery on mixed haemorrhoids,compared with Milligan-Morgan haemorrhoidectomy.Methods:A multi-centre,randomized,singleblind,non-inferiority clinical trial was performed.Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing Rectum Hospital,Air Force Medical Center of People's Liberation Army of China,and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018.By using a blocked randomization scheme,participants were assigned to two groups.The experimental group was treated with HSLI,while the control group was treated with Milligan-Morgan haemorrhoidectomy.The primary outcome was the clinical effect evaluated at 12 weeks after operation.The secondary outcomes included the number of haemorrhoids treated during the operation,pain scores,use of analgesics,postoperative oedema,wound healing,incidence of anal stenosis,anorectal manometry after operation,as well as surgical duration,length of stay and total hospitalization expenses.A safety evaluation was also conducted.Results:In total,246 eligible participants were enrolled,with 123 cases in each group.There was no significant difference in the clinical effect between the two groups(100.00% vs.99.19%,P>0.05).Compared with the control group,the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group(P<0.05 or P<0.01);the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group(P<0.05).There was no significant difference in the incidence of anal stenosis,the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation(P>0.05).The surgical duration and length of stay in the experimental group were significantly longer than those in the control group,and the total hospitalization expense was significantly higher than that in the control group(all P<0.05).No adverse events were reported in either group during the whole trial or follow-up period.Conclusion:HSLI had the advantages of preserving the skin of anal canal completely,alleviating postsurgical pain and promoting rapid recovery after operation.(Registration No.Chi CTR1900022883).JIA Xiao-qiang CAO Wei-wei QUAN Long-fang ZHAO Wei-bing CHENG Fang JIA Shan FENG Liu-quan WEI Xu-feng XIE Zhen-nian WANG Dong XU Chun-yan CUI Chun-hui CAI Xing-juan HE Lan-ye WANG Zhan-jun TIAN Ying SHI Shu-min SUN Si-miao SU Liang ZHAI Meng-fan 2021Chinese Journal of Integrative Medicine2021,27,9:11
3Rapid detection of sepsis complicating acute necrotizing pancreatitis using polymerase chain reaction显示文摘INTRODUCTIONAcute narcotizing pancreatitis usually takes a severe clinical course and is associated with multiple organ dysfunction .With the further understanding of pathophysiological events of acute pancreatisis and the therapeutic measuses taken by the clinicians ,the patients can pass through the critical carry stages ,and then the septic complication caused by rtanslocated bacteria, mostly gram-negative microbes from the intestines ensues[1].Wei Zhong Zhang1 Tian Quan Han2 Yao Qing Tang2 Sheng Dao Zhang2 1Department of Surgery. Huangyan First Hospital, Huangyan 318020, Zhejiang Province. China 2Department of Surgery. Ruijin Hospital. Shanghai Second Medical University. Shanghai 200025. ChinaDr. Wei Zhong Zhang, graduated from Shanghai Second MedicalUniversity receiving master degree of surgery in 1999 he is devoted to basic and clinical investigation on severe acute pancreatitis and has one paper published. 2001World Journal of Gastroenterology2001,7,2:7
4Strengthening mechanisms of indirect-extruded Mg-Sn based alloys at room temperature显示文摘The strength of a material is dependent on how dislocations in its crystal lattice can be easily propagated.These dislocations create stress fields within the material depending on their intrinsic character.Generally,the following strengthening mechanisms are relevant in wrought magnesium materials tested at room temperature:fine-grain strengthening,precipitate strengthening and solid solution strengthening as well as texture strengthening.The indirect-extruded Mg-8Sn(T8)and Mg-8Sn-1Al-1Zn(TAZ811)alloys present superior tensile properties compared to the commercial AZ31 alloy extruded in the same condition.The contributions to the strengthen of Mg-Sn based alloys made by four strengthening mechanisms were calculated quantitatively based on the microstructure characteristics,physical characteristics,thermomechanical analysis and interactions of alloying elements using AZ31 alloy as benchmark.Wei Li Cheng Quan Wei Tian Hui Yu Hua Zhang Bong Sun You 2014Journal of Magnesium and Alloys2014,2,4:4
5Polarization-independent all-silicon dielectric metasurfaces in the terahertz regime显示文摘Dielectric metasurfaces have achieved great success in realizing high-efficiency wavefront control in the optical and infrared ranges. Here, we experimentally demonstrate several efficient, polarization-independent, all-silicon dielectric metasurfaces in the terahertz regime. The metasurfaces are composed of cylindrical silicon pillars on a silicon substrate, which can be easily fabricated using etching technology for semiconductors. By locally tailoring the diameter of the pillars, full control over abrupt phase changes can be achieved. To show the controlling ability of the metasurfaces, an anomalous deflector, three Bessel beam generators, and three vortex beam generators are fabricated and characterized. We also show that the proposed metasurfaces can be easily combined to form composite devices with extended functionalities. The proposed controlling method has promising applications in developing low-loss, ultra-compact spatial terahertz modulation devices.HUIFANG ZHANG XUEQIAN ZHANG QUAN XU QIU WANG YUEHONG XU MINGGUI WEI YANFENG LI JIANQIANG GU ZHEN TIAN CHUNMEI OUYANG XIXIANG ZHANG CONG HU JIAGUANG HAN WEILI ZHANG 2018Photonics Research2018,9,1:4
6A novel method to prepare SPR sensor chips based on photografting molecularly imprinted polymer显示文摘准备回声(SPR ) 传感器基于 grafted 削的表面电浆子的一个新奇方法印了聚合物被探索。Benzophenone photografting 系统被用来从金底层的修改表面种分子地印的聚合物(MIP ) 电影。MIP 电影的表面形态学和厚度被扫描电子显微镜(SEM ) 调查。传感器薄片的吸附性质被 SPR 光谱学学习。结果证明 nano-MIP 电影能与模板分子的好吸附在金底层的表面上被构造。Qing Quan Wei Tian Xin Wei 2011Chinese Chemical Letters2011,22,6:3
7Recent progress on multifunctional electromagnetic interference shielding polymer composites显示文摘The explosive development of electronic devices and wireless communication technology gives rise to the issue of electromagnetic pollution,known as electromagnetic interference(EMI).The accumulation of undesirable electromagnetic radiation in space disturbs the normal function of unshielded electronic appliances and poses seriously threat to human health.Thus,the development of EMI shielding materials have emerged to solve the grim problem.Considering the complex application contexts,EMI shielding materials have evolved from traditional single-function to multi-functions to meet the ever-increasing application requirements in recent few years.This paper provides detailed insight into the current re-search status and future challenges in the advancement of polymer-based EMI shielding materials with various functions.First,the basic theory of EMI shielding,factors influencing results and the dominating characterization technologies for EMI shielding properties are summarized.Then,the comprehensive descriptions of the seven types of multifunctional EMI shields are provided with respect to their structures,fabrication methods and specific functions.Meanwhile,the corresponding critical scientific and technical issues are proposed.Based on our comprehensive analysis,the main challenges in the development of multifunctional EMI shielding materials are presented.This review aims to provide some guidance and inspire more efforts toward functional EMI shielding material research to satisfy the growing requirements for next-generation electronic systems.Ke Tian Danrong Hu Quan Wei Qiang Fu Hua Deng 2023Journal of Materials Science & Technology2023,,3:2
8THEMIS statistical study on the plasma properties of high-speed flows in Earth's magnetotail显示文摘Using Time History of Events and Macroscale Interactions during Substorms(THEMIS) observations from 2007 to 2011 tail seasons, we study the plasma properties of high speed flows(HSFs) and background plasma sheet events(BPSs) in Earth's magnetotail(|Y_(GSM)|<13R_E, |Z_(GSM)|<5R_E, –30R_EPAN Dong Xiao SUN Wei Jie SHI Quan Qi TIAN An Min YAO Zhong Hua FU Sui Yan ZONG Qiu Gang ZHOU Xu Zhi PU Zu Yin 2016Science China Earth Sciences2016,59,3:2
9Excitation to defect-bound band edge states in twodimensional semiconductors and its effect on carrier transport显示文摘The ionization of dopants is a crucial process for electronics,yet it can be unexpectedly difficult in two-dimensional materials due to reduced screening and dimensionality.Using first-principles calculations,here we propose a dopant ionization process for twodimensional semiconductors where charge carriers are only excited to a set of defect-bound band edge states,rather than to the true band edge states,as is the case in three-dimensions.These defect-bound states have small enough ionization energies but large enough spatial delocalization.With a modest defect density,carriers can transport through band by such states.Dan Wang Dong Han Damien West Nian-Ke Chen Sheng-Yi Xie Wei Quan Tian Vincent Meunier Shengbai Zhang Xian-Bin Li 2019npj Computational Materials2019,,1:1
10The mechanism of tumor angiogenesis and the effect of the antiangiogenesis factors on pancreatic cancer 显示文摘XU Zhi - wei HAN Tian -quan ZHANG Sheng - dao 2004International Journal of Digestive Disease2004,24,1:1
11Genome sequence of Gossypium anomalum facilitates interspecific introgression breeding显示文摘Crop wild relatives are an important reservoir of natural biodiversity. However, incorporating wild geneticdiversity into breeding programs is often hampered by reproductive barriers and a lack of accurate genomicinformation. We assembled a high-quality, accurately centromere-anchored genome of Gossypium anomalum, a stress-tolerant wild cotton species. We provided a strategy to discover and transfer agronomicallyvaluable genes from wild diploid species to tetraploid cotton cultivars. With a (Gossypium hirsutum 3 G.anomalum)2 hexaploid as a bridge parent, we developed a set of 74 diploid chromosome segment substitution lines (CSSLs) of the wild cotton species G. anomalum in the G. hirsutum background. This set of CSSLsincluded 70 homozygous substitutions and four heterozygous substitutions, and it collectively containedabout 72.22% of the G. anomalum genome. Twenty-four quantitative trait loci associated with plant height,yield, and fiber qualities were detected on 15 substitution segments. Integrating the reference genome withagronomic trait evaluation of the CSSLs enabled location and cloning of two G. anomalum genes thatencode peroxiredoxin and putative callose synthase 8, respectively, conferring drought tolerance andimproving fiber strength. We have demonstrated the power of a high-quality wild-species reference genomefor identifying agronomically valuable alleles to facilitate interspecific introgression breeding in crops.Zhenzhen Xu Jiedan Chen Shan Meng Peng Xu Caijiao Zhai Fang Huang Qi Guo Liang Zhao Yonggang Quan Yixin Shangguan Zhuang Meng Tian Wen Ya Zhang Xianggui Zhang Jun Zhao Jianwen Xu Jianguang Liu Jin Gao Wanchao Ni Xianglong Chen Wei Ji Nanyi Wang Xiaoxi Lu Shihong Wang Kai Wang Tianzhen Zhang Xinlian Shen 2022Plant Communications2022,3,5:1
12Comparative evaluation of surgical stress of different lymph node dissection for gastric cancer显示文摘Objective: To evaluate the effects of surgical trauma of open surgery on the patients with gastric carcinoma who underwent different lymph node dissection. Methods:Total 30 patients with gastric carcinoma were divided into three groups (D1, D2, and D3) according to the extent of lymph node dissection. Peripheral blood samples were taken to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and polymorphonuclear elastase (PMNE). Ad- ditionally, leucocytes and lymphocytes counts in peripheral serum were also detected. Results: All the three groups showed a significant increase of the levels of IL-6, IL-8, CRP and PMNE after operation. There was no significant difference between D1 and D2 groups. When the comparison was made between D3 group and the other two groups, it showed higher concentration of IL-6, IL-8, CRP and PMNE in serum of D3 group. Leucocytes count showed no difference among the three groups. After operation, the patients in three groups had transient lymphocytes decrease on the second and third postoperative days, the lymphocytes count in D3 group was still lower while those in D1 and D2 groups began to increase. Conclusion: IL-6, IL-8, CRP and PMNE can be used to monitor surgical stress. Using these parameters, we found that extended lymph node dissec- tion of D3 group led to more postoperative stress than D1 and D2 groups.Xiang Hu Shengwei Xie Wei Wen Dayu Tian Quan Bao 2007The Chinese-German Journal of Clinical Oncology2007,6,4:1
13Microsurgical treatment of posterior inferior cerebellar aneurysms based on angioarchitecture supplemented by high-resolution vessel wall MRI:a case series report显示文摘Background Surgical treatment of posterior inferior cerebellar artery(PICA)aneurysms is challenging because many are nonsaccular and atherosclerotic.We report our tailored approach to PICA aneurysms,which is based on angioarchitecture supplemented by high-resolution vessel wall MRI(HR-VW MRI)findings.Methods From March 2010 to September 2020,27 patients with 29 PICA aneurysms underwent surgical treatment in our institution.Since October 2016,HR-VW MRI has been used for aneurysmal wall assessment.Clinical characteristics,radiological data and surgical outcomes were analysed.Results Nineteen proximal PICA aneurysms(vertebral artery(VA),P1,P2 and P3)were treated using the far-lateral approach.Ten distal PICA aneurysms(P4,P5)were treated using the suboccipital midline approach.Direct clipping or clip reconstruction was achieved in 19 aneurysms.Ten were trapped in conjunction with extracranial-intracranial or intracranial-intracranial bypass,including three occipital artery-PICA reimplantations,three PICA-VA reimplantations,two PICA-PICA side-to side anastomoses,one PICA-PICA reimplantation and one PICA-PICA reanastomosis.All aneurysms were eventually completely obliterated and all bypasses remained patent.At the last follow-up,26 patients(96.2%)achieved a good outcome(modified Rankin Scale score<3).Eight patients underwent HR-VW MRI.Among these,the six aneurysms with focal wall enhancement required bypass and the two with negative enhancement were successfully clipped.Conclusion PICA aneurysms have a higher frequency of complex features such as large or giant size and fusiform or dissecting morphology.Favourable outcomes were achieved with individualised microsurgical strategies based on angioarchitecture.HR-VW MRI may be used as a promising technique to predict aneurysmal atherosclerosis.Zixiao Yang Jianping Song Kai Quan Peiliang Li Qingzhu An Yuan Shi Peixi Liu Guo Yu Yanlong Tian Liangfu Zhou Wei Zhu 2022Stroke & Vascular Neurology2022,7,4:1
14The potential of transition metal–methylidynes as high-capacity hydrogen storage media显示文摘Qi Dong Wei Quan Tian De-Li Chen Chia-Chung Sun 2009International Journal of Hydrogen Energy2009,,13:1
15Microstructural Evolution during Tensile Deformation in TRC-ZA21 Magnesium Alloy with Different Loading Directions and Strain Rates显示文摘The variation of texture characteristics and activation of deformation mechanism in magnesium alloys can be achieved by addition of RE and Ca elements and subsequently affect the microstructure evolution during deformation process.In this manuscript,the effects of loading direction and strain rate on mechanical properties,microstructural characteristics,texture evolution and deformation mechanism in TRC-ZA21 magnesium alloy sheet were investigated.Moreover,orientation dependence and strain rate sensitivity of deformation mechanism were also discussed.The results showed that evident difference in mechanical properties in TRC-ZA21 alloy exhibited by the changes in loading direction and strain rate.The variations in grain orientation and basal texture characteristic were attributed to the grain rotation behavior during the plastic deformation,dominated by deformation mechanism.Basal slip,extension twinning and prismatic slip played different contributions to plastic deformation behavior and presented orientation dependence and strain rate sensitivity.The activities of prismatic slip and extension twinning both enhance with increasing strain rate.The phenomenon of weakened effect of twinning and promoted role of prismatic slip was presented to coordinate strain compatibility during plastic deformation.Yun Zhang Chen Jiang Shaoheng Sun Wei Xu Quan Yang Yongjun Zhang Shiwei Tian Xiaoge Duan Zhe Xu Haitao Jiang 2023Acta Metallurgica Sinica(English Letters)2023,36,2:0
16A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage显示文摘BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.Tian Yan Ziyin Chen Shengdong Zou Zefan Wang Quan Du Wenhua Yu Wei Hu Yongke Zheng Keyi Wang Xiaoqiao Dong Shuangyong Dong 2023World Journal of Emergency Medicine2023,14,5:0
17Theoretical Studies on the Electronic Structure of Nano-graphenes for Applications in Nonlinear Optics显示文摘In this work,azulene is introduced into nano-graphene with coronene center to enhance the second-order nonlinear optical(NLO)properties.The sum-over-states(SOS)model based calculations demonstrate that dipolar contributions are larger than octupolar contributions to the static first hyperpolarizability(〈β0〉)in most nano-graphenes except those with high symmetry(e.g.,a C2v nano-graphene has octupolar contributionsΦJ=3 up to 59.0%of the〈β0〉).Nano-graphenes containing two parallel orientating azulenes(i.e.,Out-P and Out-Ps)have large dipole moments,while their ground state is triplet.Introducing B/N/BN atoms into the positions with a high spin density transfers the ground state of Out-P and Out-Ps to closed-shell singlet,and the Out-Ps-2N has a large〈β0〉of 1621.67×10−30 esu.Further addition of an electron donor(NH2)at the pentagon end enhances the〈β0〉to 1906.22×10−30 esu.The two-dimensional second-order NLO spectra predicted by using the SOS model find strong sum frequency generations and difference frequency generations,especially in the near-infrared and visible regions.The strategies to stabilize the electronic structure and improve the NLO properties of azulene-defect carbon nanomaterials are proposed,and those strategies to engineer nano-graphenes to be semiconducting while maintaining theπ-framework are exten-dable to other similar systems.CHEN Kaichun ZHENG Xuelian YANG Cuicui TIAN Wei Quan LI Weiqi YANG Ling 2022Chemical Research in Chinese Universities2022,38,2:0
18THE ELECTROCHEMICAL BEHAVIOURS OF SOLUBLE POLYIMIDES显示文摘THEELECTROCHEMICALBEHAVIOURSOFSOLUBLEPOLYIMIDES¥YingZHU;WeiXING;GongQuanSUN;DuGUO;MengXianDINGTianHongLUandShiQuanXI(Laborato...Ying ZHU Wei XING Gong Quan SUN Du GUO Meng Xian DING Tian Hong LU Shi Quan XI 1995Chinese Chemical Letters1995,6,2:0
19LincRNA-P21 knockdown facilitates esophageal squamous cell carcinoma cell progression by upregulating cadherin 5 via YTH domain containing 1显示文摘LincRNA-P21 is a tumor suppressor in esophageal squamous cell carcinoma(ESCC).Cell adhesion modules play vital roles in cell-cell and cell-extracellular matrix(ECM)interactions and malignant cancer progression.In this study,we investigate whether lincRNA-P21 exerts its functions by regulating the cell adhesion molecule cadherin 5(CDH5)in ESCC.Moreover,the RNA binding protein(RBP)mediators of lincRNA-P21 and CDH5 are further ex-amined.Cell viability,growth and migratory ability are assessed by calcein-AM/PI double staining,CCK-8,EdU,Transwell,and wound healing assays.The expression of collagen I and fibronectin is examined by immuno-fluorescence(IF).LincRNA-P21 and CDH5 are quantified by RT-qPCR and western blot analysis.Potential lincRNA-P21 targets are identified by RNA sequencing.RBPs that can interact with lincRNA-P21 and CDH5 are identified by RNA immunoprecipitation(RIP)assay.LincRNA-P21 knockdown increases cell viability,growth,cell migration,and collagen I and fibronectin expression in ESCC cells.LincRNA-P21 depletion induces the dysregulation of 316 genes,including CDH5,in TE-1 cells.CDH5 is identified as a downstream molecule of lincRNA-P21 given its close corre-lation with cell adhesion,ECM reconstruction,and cancer progression.LincRNA-P21 exerts its functions by nega-tively regulating CDH5 expression.YTH domain containing 1(YTHDC1)mediates the regulatory effect of lincRNA-P21 on CDH5.LincRNA-P21 knockdown elevates cell viability and growth,promotes cell migration,and induces ECM reorganization by upregulating CDH5 via RBP YTHDC1 in ESCC.Jianjun Wang Li Zhu Quan Zhang Tian Xia Wenjian Yao Li Wei 2023Acta Biochimica et Biophysica Sinica2023,55,11:0
20Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species显示文摘The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.Hui-Nan Zhang Meng Zhang Wen Tian Wei Quan Fan Song Shao-Yuan Liu Xiao-Xiao Liu Dan Mo Yang Sun Yuan-Yuan Gao Wen Ye Ying-Da Feng Chang-Yang Xing Chen Ye Lei Zhou Jing-Ru Meng Wei Cao Xiao-Qiang Li 2023Journal of Pharmaceutical Analysis2023,13,11:0
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