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AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

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中国组织工程研究 2025年第17期29卷 3537-3547页

作者： Yu Yangyi song Zhuoyue Lian Qiang Ding Kang Li Guangheng shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration Division of Adult Joint Reconstruction and Sports MedicineDepartment of Orthopedic SurgeryShenzhen People’s Hospital(The Second Clinical Medical College Jinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina Department of Orthopedics Zhengzhou Orthopedics HospitalZhengzhou 450000Henan ProvinceChina Department of Orthopedics Shenzhen Pingle Orthopedics HospitalShenzhen 518000Guangdong ProvinceChina

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent ***,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory *** studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage ***:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis ***:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were *** efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into *** experiments were divided into five groups:PBs group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 *** were collected at 4,12,and 24 weeks *** staining,including safranin O and Alcian blue,was applied after collecting articular ***,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in *** AND CONCLUsION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis *** cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(Psults also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(Psent study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal *** either p65shRNA or BMP4

关键词： osteoarthritis adeno-associated virus bone morphogenetic protein 4 p65-short hairpin RNA gene therapy short hairpin RNA transforming growth factor-β1 extracellular matrix articular cartilage chondrocytes.

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BTG2 interference ameliorates high glucose-caused oxidative stress, cell apoptosis, and lipid deposition in HK-2 cells

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BIOCELL 2024年第9期48卷 1379-1388页

作者： WENJUAN ZHU ZHENGZHENG JU FAN CUI Department of Blood Transfusion The First People’s Hospital of WuhuWuhu241000China Department of Clinical Laboratory The First People’s Hospital of WuhuWuhu241000China

Objective:Diabetic nephropathy(DN)is a deleterious microangiopathy of diabetes,constituting a critical determinant of fatality in diabetic *** work is purposed to disclose the effects and modulatory mechanism of BTG anti-proliferation factor 2(BTG2)during the pathological process of ***:BTG2 expression in kidney tissues of diabetic mice and high glucose(HG)-exposed human proximal tubular cell line HK-2 was assessed with Western blot and *** diabetic mice model was constructed by streptozotocin injection and confirmed by the blood glucose level beyond 16.7 mmol/*** and eosin(H&E)staining and measurement of kidney function hallmarks were conducted to assess kidney *** counting kit(CCK)-8 method and TUNEL assay appraised cell activity and *** red O staining assayed lipid *** commercial kits were used to estimate oxidative stress-related ***-immunoprecipitation(Co-IP)assay testified the binding relationship of BTG2 with protein arginine methyltransferase 1(PRMT1).Results:BTG2 expression was significantly raised in renal tissues of diabetic mice and HK-2 cells exposed to ***2 deficiency improved viability and extenuated the apoptosis,lipid deposition as well as oxidative stress in HK-2 cells following HG *** addition,PRMT1 was also overexpressed in HK-2 cells exposed to ***2 interacted with PRMT1 and positively modulated PRMT1 *** effects of BTG2 interference on viability,apoptosis,lipid deposition,and oxidative stress in HG-challenged HK-2 cells were partially abrogated by PRMT1 ***:Altogether,BTG2 might aggravate HK-2 cell injury in response to HG by binding with PRMT1,providing a novel target for the therapeutic strategy of DN.

关键词： BTG2 Diabetic nephropathy Lipid deposition Oxidative stress PRMT1

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Identification prognostic features related to sphingolipid metabolism and experimental validation of TRIM47 in hepatocellular carcinoma

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BIOCELL 2024年第4期48卷 639-651页

作者： JIAN TANG CHENQIANG ZHU YUN CHEN YUNLONG WU MING HE YI ZHOU MINGHUA XIE Department of Intensive Care Unit The First People’s Hospital of Linping DistrictHangzhouChina Department of Pharmacy The First People’s Hospital of Linping DistrictHangzhouChina

Background:The speciﬁc impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains *** study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug ***:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GsE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)*** classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were ***,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso *** expression of 8 risk genes was veriﬁed in ***:8 risk genes were used to construct the sphingolipid score ***-sphingolipid score predicted poor prognosis of HCC *** score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDsC,Neutrophil,Fibroblasts and macrophage),and MAPK *** the High-sphingolipid score group,a signiﬁcantly higher proportion of patients with TP53(p53)mutations was signiﬁcantly higher(56%).Furthermore,patients with a high-sphingolipid score were predicted to have a higher sensitivity to chemotherapy *** vitro validation showed that compared with normal liver cells LX-2,TRIM47,and s100A9 signiﬁcantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while sLC1A7,LPCAT1,and CFHR4 signiﬁcantly *** TRIM47 reduced the proliferation and promoted *** levels of ceramide synthesis-related indexes(CERs1,CERs6,CERs5,and sPTLC2)increased,and the ACER3 related to catalytic hydrolysis ***:We constructed a sphingolipid metabolism-related prognostic signature(sphingolipid score)based on 8 risk ***47 may affect the development of liver cancer by regulating the relevant indicators of

关键词： Hepatocellular carcinoma sphingolipid metabolism TRIM47 Prognosis

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Protective effect of penehvclidine hvdrochloride on ischemiareperfusion injury in rats

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Asian Pacific Journal of Tropical Medicine 2014年第1期7卷 67-70页

作者： Zhen su Wei Cai Department of Anesthesiology Huai'an First People's HospitalNanjing Medical Unversity Department of Orthopedics Huai'an First People's HospitalNanjing Medical Unversity

Objective:To investigate the protective effect of penehvclidine hvdrochloride on ischemiareperfusion injury in ***:The model of ischemia-reperniston injury was established in rats through clamping rental pedicles for sO min followed by reperfusion.A total of 60 Wistar rats were randomly *** 4 groups including fake surgery group,model group,low PHC dosage group and high dosage penehvclidine hvdrochloride(PHC)*** days before the experiment,rats in fake surgery group and model group were given 10 mL/kg normal saline,while rats in low PHC dosage group and high dosage PHC group were given 200 and sO mg/kg PHC,*** urine volume,diet volume,Cre,PU,BUN,IL-6,IL-8,TNF-α,NO MDA concentration,sOD and GsH-Px were ***:Compared with rats in model group,decreased urine volume,diet volume,Cre,PU,BUN,IL-6,IL-8,TNF-α,NO MDA concentration and increased sOD and CsH-Px activity could be seen in low PHC dosage group and high dosage PHC group(Psions:Administration of PHC before ischemia-reperfusion injury can help protect ischemia-reperfusion injury.

关键词： Penehvclidine hydrochloride Rental ischemia-reperfusion injury Inflammation factor Radical

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Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound

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Hepatobiliary & Pancreatic Diseases International 2016年第1期15卷 48-54页

作者： Yi Dong Zheng Zhu Wen-Ping Wang Feng Mao Zheng-Biao Ji Department of Ultrasound Zhongshan HospitalFudan University Department of Ultrasound Taicang First People’s Hospital

BACKGROUNI）： Hepatocellular adenoma （HCA） is a rare benign tumor of the liver. It is of clinical importance to dif- ferentiate HCA from other liver tumors, especially hepatocel- lular carcinoma （HCC）. This study aimed to evaluate the char- acteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound （CEUs） findings. METHODs： Twenty-six patients （10 males and 16 females; mean age 36.2＋5.0 years） with 26 histopathologically proven HCAs were retrospectively identified. According to the maxi- mum diameter of HCAs, they were divided into three groups：〈30 mm, 30-50 mm, and 〉50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit （Philips Bothell, WA, UsA）. For each lesion, a dose of 2.4 mL sonoVue~ （Bracco Imaging spa, Milan, Italy） was injected as a quick bolus into the cubital vein. Lesions＇ echogenicity, color-Doppler flow imaging and contrast en- hancement patterns were recorded. REsULTs： Grayscale ultrasound revealed that most of HCAs were hypoechoic （73.1%, 19/26）. spotty calcifications were detected in 26.9% （7/26） of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% （12/26） of the HCAs. CEUs showed that 73.1% （19/26） of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% （14/26） showed decreased contrast enhancement in the late phase. There was no significant difference in enhance- ment patterns among different sizes of HCAs （P〉0.05）. Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs.

关键词： contrast-enhanced ultrasound hepatocellular adenoma ultrasound diagnosis

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Preoperative diabetes as a protective factor for pancreatic fistula after pancreaticoduodenectomy: a meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2015年第2期14卷 132-138页

作者： Xiang Xia Chen Huang Gang Cen Zheng-Jun Qiu Department of General surgery Shanghai Jiaotong University Affiliated First People's Hospital

BACKGROUND： The role of diabetes mellitus （DM） in pancreatic fistula （PF） or clinical relevant PF （CR-PF） after pancreaticoduodenectomy （PD） or pylorus-preserving pancreaticoduodenectomy （PPPD） is unclear. We conducted a meta-analysis to investigate the relationship between DM and PF or *** sOURCEs： Embase, MEDLINE and Cochrane databases were searched systematically for relevant articles from January 2005 to June 2013. The selected studies that examined clinical risk factors of PF or CR-PF were included. We created pooled estimates for our outcomes using the random-effects model. REsULTs： sixteen observational clinical studies were included. Pooling of PF rates from ten studies revealed that DM was associated with a decreased risk of PF （P=0.01）. CR-PF rates from 8 studies showed no significant difference between DM and control group （P=0.14）. CONCLUsIONs： DM is not a risk factor for PF in patients undergoing PD or PPPD. On the contrary, patients without DM are at a higher risk of PF because the pancreases in these patients have more fatty tissue and the pancreas is soft.

关键词： pancreatic fistula diabetes postoperative complication

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Apoptosis and Fas system Are significantly Involved in the Process of Liver Cirrhosis Converting into Hepatocellular Carcinoma

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Journal of Huazhong University of science and Technology(Medical sciences) 2001年第2期21卷 126-129,148页

作者：彭志海唐华美凌云韩国新 Department of General surgery Shanghai First People''s Hospital Shanghai 200080

To investigate the roles of apoptosis and the Fas system in the process of liver cirrhosis converting into hepatocellular carcinoma , expression of Fas and Fas ligand in 49 LC and 36 HCC samples was detected by immunohistochemical method. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method. serum soluble Fas levels in 28 cases of LC and 27 cases of HCC were measured by enzyme linked immunosorbent assay method. Compared with LC, apoptotic indices in HCC tissues were significantly reduced , expression of Fas was decreased , and that of FasL was increased . serum sFas levels in HCC patients were significantly higher than those in normal controls. Down regulation of Fas expression, up regulation of FasL expression in hepatocytes and elevation of sFas level in serum might contribute to tumor escape from immune surveillance of the body. Apoptosis and the Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

关键词： hepatocellular carcinoma liver cirrhosis apoptosis Fas Fas ligand soluble Fas

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A case of spermatic cord cyst with nodular histiocytic/mesothelial hyperplasia

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Asian Journal of Andrology 2017年第4期19卷 505-506页

作者： Hong-Jie Chen Dong-Hai Li Jun Zhang Department of Urology The First People's Hospital of Lanzhou Lanzhou 730050 China Department of Pathology The First People's Hospital of LanzhouLanzhou 730050 China

Dear Editor, Nodular histiocytic/mesothelial hyperplasia （NHMH） is a rare and benign tumor-like lesion and easily misdiagnosed clinically and pathologically. We report a case of right spermatic cord cyst with NHMH.

关键词： spermatic histiocytic hyperplasia

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Current concept of pathogenesis of severe acute pancreatitis

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World Journal of Gastroenterology 2000年第1期6卷 32-36页

作者： Wu XN Department of Gastroenterology Shanghai First People's HospitalShanghai 200080China

The pathogenesis of severe acute pancreatitis isvery *** is a multifactorial as well asmultifaceted *** of all,the etiologicagents initiate the pancreatic acinar injury by releaseof pancreatic enzymes and overstimulat... 详细信息

关键词： subject headings pancreatitis/etiology pancreatitis/diagnosis pancreatitis/pathophysiology

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Heparanase-1 activities in the development of laser induced choroidal neovascularization

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 131-135页

作者： Wei-Qiang Tang Bao-Ke Hou Department of Ophthalmology the First Affiliated Hospital of General Hospital of People's Liberation Army General hospital of people's Liberation Army

AIM: To investigate the role of heparanase-1 in laser-induced choroidal neovascularization (CNV). METHODs: Experimental CNV was induced by krypton laser photocoagulation in 15 male Brown Norway rats. Fundus fluorescein angiography and histopathological examination were performed in observing the CNV development. The expression and distribution of heparanase-1 protein in the laser lesions were determined by immunohistochemistry and western blotting analysis. REsULTs: The success rate of laser induced CNV was approximately 75% on 3-4 weeks after laser photo-coagulation. The protein levels of heparanase-1 increased significantly in the retina-choroidal complex of CNV models when compared to normal rat eyes (P staining confirmed strong heparanase-1 expressions in all laser lesions, and it displayed to be highest at the newly formed blood vessels within the fibrovascular complex in the subretinal space. CONCLUsION: Heparanase-1 is closely involved in the development of laser induced CNV.

关键词： choroidal neovascularization immunohistochemistry western blotting heparanase-1

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