1.Advances in researches on β-carbonic anhydrases as anti-parasitic drug tar-gets
Chinese Journal of Schistosomiasis Control 2016;(1):99-102
β?carbonic anhydrases(β?CAs)are ubiquitous metalloenzymes which active site contains a zinc ion(Zn2+),and they could catalyze the hydration of carbon dioxide to bicarbonate and protons efficiently and are involved in many biological pro?cesses,such as respiration,pH and CO2 homeostasis,biosynthetic reactions,virulence regulation and so on,and may play a critical role in the life activity of many organisms which contain these enzymes. β?CAs are widely distributed in fungi,bacteria, algae,plants and a small number of protozoan and metazoan except vertebrates. Therefore,as potential drug targets for design?ing and developing antibacterial and anti?parasitic drugs,β?CAs promise a broad application prospect. This paper focuses on the distribution,physiological function and the progress of researches on β?CAs in parasites and their vectors.
2.Safety Evaluation of Morphine Hydrochloride Injection
Wenzhi WEI ; Jichao SUN ; Conghui ZHU ; Minjuan ZHANG ; Tianxue WANG
Herald of Medicine 2019;38(2):159-162
Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2% rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.
3.Prostate artery embolization and transurethral resection of prostate for benign prostatic hyperplasia: A prospective randomized controlled trial
Conghui ZHU ; Wenji LIN ; Zhiyang HUANG ; Jingshuang CAI
Chinese Journal of Interventional Imaging and Therapy 2018;15(3):134-138
Objective To evaluate the efficacy and safety of prostatic arterial embolization (PAE) and transurethral resection of prostate (TURP) in treatment of benign prostatic hyperplasia (BPH).Methods Totally 40 patients with BPH from Jan 2016 to Oct 2016 were selected.All patients were divided into PAE (n=20) and TURP (n=20) group by random number table method.The curative effect indexes (international prostate symptom score [IPSS],quality of life score [QOL],prostate volume [PV],postvoid residual [PVR],maximum urinary flow rate [Qmax] and prostate-specific antigen [PSA]),the complications and side effects,as well as the incidence of sexual dysfunction were analyzed and compared between the two groups.Results No statistical difference of IPSS,QOL,PV,PVR,Qmax nor PSA was found between the two groups before operation (all P>0.05).IPSS,QOL,PV,PVR and PSA were significantly lower than those before operation 3,6 and 12 months after operation (all P<0.05),while Qmax was obviously higher than that before operation (P<0.05).Three months after operation,the curative effect indexes were statistically different between the two groups (all P<0.05),while no statistical difference was found 6 and 12 months after operation (P>0.05).The incidence of postoperative complications in TURP group was higher than that in PAE group (x2 =4.329,P=0.037).There was no statistical difference in the incidence of sexual dysfunction between the two groups (x2=2.105,P=0.147).Conclusion PAE and TURP can significantly alleviate clinical symptoms of patients with BPH.Three months after operation,the efficacy of TURP is better than PAE,but PAE is more minimally invasive and has fewer complications.
4.Effects of Compound Kushen Tang on Ulcerative Colitis in Rats and the Underlying Mechanism
Chengzhi ZHOU ; Nan JIANG ; Conghui ZHOU ; Wanjin SUN ; Wei SUN ; Xiulan WANG ; Tianmi ZHU ; Songtao WU ; Jia YANG ; Xueyun DUAN ; Heng FAN
China Pharmacist 2016;19(10):1816-1820
Objective: To investigate the therapeutic effects of compound Kushen Tang and its relevant mechanism in TNBS-in-duced ulcerative colitis ( UC) rats. Methods:UC was induced by TNBS in rats. After compound Kushen Tang was given orally, the levels of MDA, iNOS, and NO and the activity of MPO, SOD, and GSH-Px were measured. The general condition of rats and colon tissue morphology were observed. Results:The levels of MDA (P<0. 05), iNOS (P<0. 01) and NO (P<0. 01) and the activity of MPO (P<0. 01) in tissues of UC rats were significantly higher than the control group. The activity of SOD (P<0. 01) and GSH-Px (P<0. 05) were significantly lower than those in the control group. After the treatment with high doses of compound Kushen Tang, the levels of MPO (P<0. 01), MDA (P<0. 05), iNOS (P<0. 05) and NO (P<0. 01) were significantly decreased, and the activity of SOD (P<0. 01) and GSH-Px (P<0. 05) significantly increased. The therapeutic effect was dose-dependent and the general con-dition of rats and colon tissue morphology were also significantly improved. Conclusion:Compound Kushen Tang is considered as a no-vel therapeutic alternatives for the treatment of UC, which can reduce coloni inflammatory injury and ameliorate the colitis.
5.Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma
Xinyuan LIU ; Ying YANG ; Chaodan YANG ; Zhengxiao MA ; Conghui WU ; Chen XU ; Rui ZHU ; Pan LIU ; Lisha YING ; Wenjuan YIN ; Dan SU
Chinese Journal of Oncology 2024;46(11):1029-1037
Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P<0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P<0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P<0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P<0.001; ρ=0.28, P<0.001; ρ=0.32, P<0.001; ρ=0.21, P=0.004; ρ=0.32, P<0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P<0.001; r=0.231, P=0.002; r=0.258, P<0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P<0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.
6.RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
WEI XINYI ; WANG CONGHUI ; TANG SANGSANG ; YANG QIAN ; SHEN ZHANGJIN ; ZHU JIAWEI ; CHENG XIAODONG ; WANG XINYU ; XIE XING ; XU JUNFEN ; LU WEIGUO
Journal of Zhejiang University. Science. B 2024;25(7):581-593,中插4-中插16
Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.
7.Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma
Xinyuan LIU ; Ying YANG ; Chaodan YANG ; Zhengxiao MA ; Conghui WU ; Chen XU ; Rui ZHU ; Pan LIU ; Lisha YING ; Wenjuan YIN ; Dan SU
Chinese Journal of Oncology 2024;46(11):1029-1037
Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P<0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P<0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P<0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P<0.001; ρ=0.28, P<0.001; ρ=0.32, P<0.001; ρ=0.21, P=0.004; ρ=0.32, P<0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P<0.001; r=0.231, P=0.002; r=0.258, P<0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P<0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.