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Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 744-757页

作者： Lifan Lin Xinmiao Li Yifei Li Zhichao Lang Yeping Li Jianjian Zheng Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China Department of Urology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China

Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with *** Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC ***,the potential role of GRb1 in mediating HSC ferroptosis remains *** study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 *** findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)***,GRb1 significantly alleviated CCl4-induced liver fibrosis in *** a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of ***,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit *** experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by ***,BECN1 could directly interact with SLC7A11,initiating HSC *** conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in ***,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.

关键词： Ginsenoside Rb1 Ferroptosis Liver fibrosis Hepatic stellate cells

Repeatability and reproducibility of corneal higher-order aberrations measurements after small incision lenticule extraction using the Scheimpfug-Placido topographer

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Eye and Vision 2024年第1期10卷 1-9页

作者： Rui Ning Rongrong Gao David PPiñero Jun Zhang Qingyi Gao Yili Jin Yiran Wang Chenxiao Wang Jinhai Huang Eye Hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhouZhejiangChina Eye Institute and Department of Ophthalmology Eye and ENT HospitalFudan UniversityShanghaiChina Group of Optics and Visual Perception Department of OpticsPharmacology and AnatomyUniversity of AlicanteAlicanteSpain NHC Key Laboratory of Myopia(Fudan University) Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghaiChina Shanghai Research Center of Ophthalmology and Optometry ShanghaiChina

Background:To evaluate the precision of corneal higher-order aberrations measurements after small incision lenticule extraction(SMILE)using the Sirius Scheimpfug-Placido topographer(CSO,Italy).Methods:Seventy-fve eyes from 75 postoperative subjects were included in this prospective *** consecutive corneal aberrometric measurements were obtained with the Scheimpfug-Placido topographer by two experienced operators to assess intra-and inter-observer *** within-subject standard deviation(Sw),test-retest repeatability(TRT)and the intraclass correlation coefcient(ICC)were ***:For intraobserver repeatability of anterior and total corneal aberrations,all ICCs were more than 0.922,except for trefoil(0.722 to 0.768).The ICCs of total root mean square(RMS),coma Z(3,±1),and spherical aberration Z(4,0)were over 0.810 while higher-order RMS,trefoil Z(3,±3),and astigmatism II Z(4,±2)were below 0.634 for posterior corneal surface *** Sw values for all types of aberrations were equal to or below 0.07μ*** interobserver reproducibility,all TRT values were no more than 0.12μm,0.05μm,and 0.11μm for anterior,posterior,and total corneal aberrations,*** ICC values ranged from 0.875 to 0.989,from 0.686 to 0.976 and over 0.834 for anterior,posterior,and total corneal aberrations,***:The repeatability of measurements of anterior and total corneal aberrations with the Sirius system in corneas after SMILE surgery was high,except for *** was some variability in posterior corneal aberrometric *** reproducibility of corneal aberrometric measurements was observed between measurements of both examiners,except for trefoil,with poor to moderate reproducibility.

关键词： Sirius Higher-order aberrations Repeatability Reproducibility Small incision lenticule extraction

Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway

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Chinese Journal of Natural Medicines 2024年第4期22卷 318-328页

作者： YE Qiaobei ZHU Yu SHI Meng LV Linxi GONG Yuyan ZHANG Luyao YANG Lehe ZHAO Haiyang ZHAO Chengguang XU Huanhai Affiliated Yueqing Hospital Wenzhou Medical UniversityWenzhou 325600China The Institute of Life sciences Biomedical Collaborative Innovation Center of Zhejiang ProvinceWenzhou UniversityWenzhou 325035China School of Pharmaceutical sciences Wenzhou Medical UniversityWenzhou 325035China

Double cortin-like kinase 1(DCLK1)exhibits high expression levels across various cancers,notably in human colorectal cancer(CRC).Diacerein,a clinically approved interleukin(IL)-1βinhibitor for osteoarthritis treatment,was evaluated for its impact on CRC proliferation and migration,alongside its underlying mechanisms,through both in vitro and in vivo *** study employed MTT assay,colony formation,wound healing,transwell assays,flow cytometry,and Hoechst 33342 staining to assess cell proliferation,migration,and ***,proteome microarray assay and western blotting analyses were conducted to elucidate diacerein’s specific mechanism of *** findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in *** high-throughput proteomics microarray and molecular docking studies,we identified that diacerein directly interacts with ***,the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was ***,diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets,including MCL-1,VEGF,and survivin,thereby inhibiting CRC progression in a mouse model,thereby inhibiting CRC progression in a mouse model.

关键词： DCLK1 Diacerein Rhein STAT3 Colorectal cancer

Clinical efficacy and computed tomography diagnostic value of bedaquiline-containing regimens in the treatment of drug-resistant pulmonary tuberculosis

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iLABMED 2024年第3期2卷 149-156页

作者： Saiduo Liu Xinchun Ye Fang Cheng Kaijia Wu Jiandan Yu Hongye Ning Jichan Shi Hongzhou Lu Wei Chen Department of Infectious Diseases Dingli Affiliated College of Wenzhou Medical UniversityWenzhou Central HospitalWenzhou Sixth People's HospitalWenzhouZhejiang ProvinceChina Department of Infectious Disease The 1st School of MedicineSchool of Information and EngineeringThe 1st Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Radiology The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Objective:This study investigated the clinical efficacy of bedaquilinecontaining regimens in the treatment of drug-resistant pulmonary tuberculosis and the diagnostic value of computed tomography(CT).Methods:We retrospectively analyzed the clinical diagnosis,treatment,and CT imaging data of patients with drug-resistant pulmonary tuberculosis treated in wenzhou Central Hospital from 1 January to 31 December *** to whether the treatment regimen contained bedaquiline,the patients were divided into an observation group(bedaquiline tablets t background regimen)and a control group(background regimen).The clinical efficacy and pulmonary CT changes before and after treatment were analyzed in both ***:After 24 weeks of treatment,there was no statistically significant difference in the white blood cell count or concentrations of hemoglobin,alanine aminotransferase,serum albumin,or creatinine between the two groups(t=0.71,0.93,0.05,0.18,and 0.08,respectively;p>0.05).After 4,8,and 12 weeks of treatment,there was no statistically significant difference in the sputum culture-negative conversion rate between the two groups(χ^(2)=2.67,0.48,and 1.82,respectively;p>0.05).At 24 weeks of treatment,the sputum culture-negative conversion rate in the observation group reached 100%,which was significantly higher than that in the control group(χ^(2)=3.97,p<0.05).The effective absorption rates on chest imaging in the two groups of patients at 12 weeks were 83.33% and 57.89%,*** 24 weeks of treatment,the effective absorption rates were 88.00% and 65.85% in the two groups,with a statistically significant difference(χ^(2)=3.98;p<0.05).There were significant differences in cavity absorption at 24 weeks(χ^(2)=4.33,p<0.05)and 48 weeks after treatment(χ^(2)=10.63,p<0.05).Conclusion:The addition of bedaquiline to the background regimen improved the sputum culture-negative conversion rate and chest imaging effective *** achieved good results at the end of t

关键词： bedaquiline tablets computed tomography drug‐resistant pulmonary tuberculosis efficacy pulmonary tuberculosis

miR-128a介导的磷酸果糖激酶通过糖代谢促进非小细胞肺癌增殖的机制研究

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Journal of Chinese Pharmaceutical sciences 2024年第5期33卷 430-437页

作者：张翔应骏磊倪江伟温州医科大学第一附属医院胸外科浙江温州325000

探讨miR-128a介导的磷酸果糖激酶通过糖代谢促进非小细胞肺癌增殖的机制。采用生信分析方法预测与PFK作用的miRNA;采用定量PCR方法(qRT-PCR)方法在肿瘤组织和细胞样本上验证该分子表达量;改变该分子表达量,分别使用免疫荧光、Western bl... 详细信息

探讨miR-128a介导的磷酸果糖激酶通过糖代谢促进非小细胞肺癌增殖的机制。采用生信分析方法预测与PFK作用的miRNA;采用定量PCR方法(qRT-PCR)方法在肿瘤组织和细胞样本上验证该分子表达量;改变该分子表达量,分别使用免疫荧光、Western blotting检测肺癌细胞的凋亡程度、PFK及低氧诱导因子1-α(hypoxia-inducible factor 1α,HIF1-α)表达水平。结果显示,生信分析显示miR-128a可以靶向PFK;miR-128a在肺癌细胞中表达量明显降低,过表达其水平,细胞凋亡数目增多,而PFR、HIF1-α蛋白表达水平降低。结果说明miR-128a在肺癌中表达降低,通过降低PFK、HIF1-α表达促进了细胞增殖。

关键词：非小细胞肺癌 miR-128a 磷酸果糖激酶增殖

FGF21 increases the sensitivity of hepatocellular carcinoma to sorafenib under hypoxia

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Malignancy Spectrum 2024年第2期1卷 99-112页

作者： Ting Zhang Huiling Shi Shihui Zhang Qin Zhu Mengyuan Qiu Ashleigh T.Chitakunye Hanyu Hong Liaoxin Luo Yujing Li Qiuyu Sun Xiaokun Li Lin Cai Department of Biopharmaceuticals School of Pharmaceutics SciencesWenzhou Medical UniversityWenzhouZhejiangChina

Background:Hepatocellular carcinoma(HCC)is a common disease in human history and one of the main causes of cancer-related *** oxygen supply in the tumor microenvironment forces cancer cells to survive in a mild hypoxia *** growth factor 21(FGF21),a member of the FGF family,has become the focus of public attention due to its outstanding achievements in diabetes and lipid ***,the mechanism of FGF21 in HCC remains ***:The aims of this study were to clarify whether or not FGF21 could increase the sensitivity of HCC to sorafenib(SORA)under hypoxia and explore the possible ***:In this study,by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide cell viability test,plate clone formation test,western blot analysis,Hoechst/propidium iodide double staining experiment,flow cytometry,quantitative reverse transcription polymerase chain reaction,and subcutaneous tumor transplantation in mice,we studied the effects of recombinant human FGF21 combined with SORA on hepatoma cells in vitro and in ***21 could enhance the phosphorylation of mothers against decapentaplegic homolog 3(Smad3)under anaerobic *** combined with SORA,FGF21 could increase the sensitivity of hepatoma cells to SORA and inhibit the growth and migration of hepatoma ***:FGF21 may increase the sensitivity of HCC to SORA by enhancing the phosphorylation of Smad3 through the phosphatidylinositol 3-kinase/protein kinase B pathway under ***:Our study suggested the possibility of combination therapy for SORA and FGF21 on HCC.

关键词： FGF21 sorafenib drug resistance hypoxia Smad3

Dynamic prediction of landslide life expectancy using ensemble system incorporating classical prediction models and machine learning

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Geoscience Frontiers 2024年第2期15卷 202-219页

作者： Lei-Lei Liu Hao-Dong Yin Ting Xiao Lei Huang Yung-Ming Cheng Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring Ministry of EducationSchool of Geosciences and Info-PhysicsCentral South UniversityChangsha 410083China College of Civil Engineering and Architecture Wenzhou UniversityWenzhou 325035China Key Laboratory of Engineering and technology for Soft Soil Foundation and Tideland Reclamation of Zhejiang Province Wenzhou 325035China wenzhou Key Laboratory of Traffic Piezoelectric Engineering technology Wenzhou 325035China Zhejiang International science and technology Cooperation Base of Ultra-soft Soil Engineering and Smart Monitoring Wenzhou 325035China School of Civil Engineering Qingdao University of TechnologyQingdao 266033China

With the development of landslide monitoring system,many attempts have been made to predict landslide failure-time utilizing monitoring data of *** models(e.g.,Verhulst,GM(1,1),and Saito models)that consider the characteristics of landslide displacement to determine the failuretime have been investigated *** practice,monitoring is continuously implemented with monitoring data-set updated,meaning that the predicted landslide life expectancy(i.e.,the lag between the predicted failure-time and time node at each instant of conducting the prediction)should be re-evaluated with *** manner is termed“dynamic prediction”.However,the performances of the classical models have not been discussed in the context of the dynamic prediction *** this study,such performances are investigated firstly,and disadvantages of the classical models are then reported,incorporating the monitoring data from four real ***,a more qualified ensemble model is proposed,where the individual classical models are integrated by machine learning(ML)-based *** evaluate the quality of the models under the dynamic prediction,a novel indicator termed“discredit index(b)”is proposed,and a higher value of b indicates lower prediction *** is found that Verhulst and Saito models would produce predicted results with significantly higher b,while GM(1,1)model would indicate results with the highest mean absolute ***,the ensemble models are found to be more accurate and qualified than the classical ***,the performance of decision tree regression-based ensemble model is the best among the various ML-based ensemble models.

关键词： Dynamic prediction Landslide life expectancy Machine learning Ensemble system

Comprehensive evaluation of intravitreal conbercept versus half-dose photodynamic therapy for chronic central serous chorioretinopathy

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International Journal of Ophthalmology(English edition) 2021年第5期14卷 719-724页

作者： Jian-Bo Mao Cai-Yun Zhang Chen-Yi Liu Yun Zhang Jing-Jing Lin Zhao-Kai Xu Yi-Qi Chen Yuan-Yuan Fan Shi-Xin Zhao Li-Jun Shen Eye Hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Chicago College of Optometry Midwestern UniversityDowners GroveIL 60515USA

AIM:To compare the safety and efficacy of conbercept intravitreal injection and half-dose photodynamic therapy(PDT)in treating chronic central serous chorioretinopathy(CSC).METHODS:This study was ***-seven patients(37 eyes)with chronic CSC received conbercept injections while 57 patients(57 eyes)were treated with half-dose *** subjects were followed in *** measures included change in best-corrected visual acuity(BCVA),central macular thickness(CMT),subfoveal choroidal thickness(SFCT),and resolution of subretinal fluid(SRF).RESULTS:There was no adverse event observed in either treatment *** the 6-month follow-up,26 eyes(70.3%)in the conbercept group and 54 eyes(94.7%)in the half-dose PDT group(P0.05).The SFCT also improved in all subjects(P<0.001)with better outcome in the half-dose PDT group(P<0.05).CONCLUSION:Both intravitreal conbercept and halfdose PDT are safe to use in treating chronic *** 6mo,both treatment groups are efficacious in improving BCVA,reducing CMT and SFCT,and resolving SRF in eyes with chronic ***-dose PDT may show better outcome at initial phase of treatment in chronic *** follow-up period is necessary to study for long-term effect and safety.

关键词： central serous chorioretinopathy conbercept photodynamic therapy subfoveal choroidal thickness

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

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Asian Journal of Andrology 2012年第5期14卷 687-690页

作者： Wu-Hua Ni Lei Jiang Qian-Jin Fei Jian-Yuan Jin Xu Yang Xue-Feng Huang Reproductive Medicine Center The First Affiliated Hospital of Wenzhou Medical CollegeWenzhou 325000China Laboratory of Internal Medicine The First Affiliated Hospital of Wenzhou Medical CollegeWenzhou 325000China

Congenital bilateral absence of the vas deferens （CBAVD） is a frequent cause of obstructive azoospermia, and mutations of the cystic fibrosis transmembrane conductance regulator （CFTR） gene have also been frequently identified in patients with CBAVD. However, the distribution of the CFTR polymorphisms M470V, poly-T, TG-repeats and F508del mutation in the Chinese CBAVD population with presumed low cystic fibrosis （CF） frequency remains to be evaluated. Samples obtained from 109 Chinese infertile males with CBAVD and 104 normal controls were analyzed for the presence of CFTR （TG）m（T）n, M470V and F508del by PCR amplification followed by direct sequencing. Our study showed that the F5OSdel mutation was not found in our patients. The 5T mutation was present with high frequency in Chinese CBAVD patients and IVS8-5T linked to either 12 or 13 TG repeats was highly prevalent among CBAVD patients （97.22% of 72 cases and 96.91% of 97 alleles with IVS8-5T）. Moreover, a statistically significant relationship between TG 12-5T-V470 haplotype and CBAVD was detected. This study indicated that the CFTR polymorphisms poly-T, TG-repeats and M470V might affect the process of CBAVD in the Chinese population.

关键词： CFTR congenital bilateral absence of the vas deferens IVS8-5T male infertility M470V