2.Advances in HIV-1 latency-regulating agents
Jiao-jiao DAI ; Xiang-yi JIANG ; Da FENG ; Hao LIN ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(4):840-852
At present, there is no cure for acquired immune deficiency syndrome (AIDS) due to HIV-1 latent reservoirs. Therefore, it urgently requires novel HIV-1 latency-regulating agents with high potency, low toxicity and favorable drug-like properties to achieve a functional cure for AIDS. Herein, we reviewed the advances in HIV-1 latency-regulating agents since 2019, including the drug discovery strategies, bioactivities, and mechanisms of these compounds. It is of great guiding significance in the development of latency-regulating agents with clinical value.
3.Loss of heterozygosity of microsatellite DNA on 6q in bladder tumor
Fan CHENG ; Yong-lie CHU ; Da-lin HE ; Lin YANG ; Ping CHEN ; E YANG ; Xiang LIU
Chinese Journal of Rehabilitation Theory and Practice 2004;10(5):279-280
ObjectiveTo investigate the loss of heterozygosity (LOH) on 6q in bladder tumor.MethodsD6S404 and D6434 microsatellite markers near 6q21 were tested by PCR-SSLP-stain method on tumor DNA from 31 cases of bladder tumor.ResultsAmong these 31 cases of bladder tumor,LOH was detected in tumor tissues on site for D6S404 (35.5%) and D6S434(22.6%).ConclusionOne or more tumor suppressor gene near 6q21 maybe relevant for the development of bladder tumor.
4.Epidemiological prospective studies on physical activities and the risk of colon cancer: a Meta-analysis
Wan-Shui YANG ; Yu-Ting TAN ; Da-Ke LIU ; Shan GAO ; Jing GAO ; Yong-Bing XIANG
Chinese Journal of Epidemiology 2010;31(9):1035-1040
Objective To explore the relationship between physical activity(PA) and the risk of colon cancer. Methods Cohort studies on physical activity and risk of colon cancer were identified by searching MEDLINE, EMBASE, Chinese Bio-medicine and Chinese Wanfang databases from January 1979 to December 2009. Results from the individual studies were synthetically combined in our study. Inverse variance weighting was used in fixed effects model and the random effects estimate was based on the DerSimonian-Laird method. Variance-weighted least squares method was used for trend test of summarized dose-response data. Results A total of 28 studies were included in our analysis. An inverse association between physical activities and the risk of colon cancer was observed with the relative risks (RR) as 0.75 [95% confidence interval (CI): 0.66-0.86] in males and 0.85(95%CI: 0.76-0.95)in females, respectively. However, the findings from those documents with high quality showed significant and borderline significant associations between PA and colon cancer in both males (RR=0.74, 95% CI: 0.61-0.90) and females (RR=0.99, 95% CI: 0.95-1.02). Meanwhile, the dose-response trend was not observed either in males (P=0.142) or in females (P=0.417). For men, the pooled RRs differed by subsites were 0.62(95%CI:0.45-0.85) and 0.74 (95%CI:0.56-0.99)for highest level PA, compared with lowest level PA in proximal colon and distal colon cancer,respectively. For women, the pooled RRs were 0.84 (95%CI: 0.69-1.01 ) in proximal colon and 0.75(95%CI: 0.53-1.05)in distal colon cancer, respectively. Conclusion These results added to the evidence for the protective effects in colon cancer among men and women.
5.Development of three-dimensional visual neurosurgical station and its preliminary clinical practice
Yi-Zhao CHEN ; Da-Yong HUANG ; Ru-Xiang XU ; Yong-Geng NIE ; Xiang-Yu WANG ; Shi-Zhong ZHANG ; Yi-Quan KE
Chinese Journal of Neuromedicine 2012;11(9):891-894
Objective To develop a three-dimensional visual neurosurgical tool enjoying simple,fast and accurate characteristics at moderate cost for visual positioning and imaging information storage and processing. Methods Seven patients with epidural hematoma or depressed fracture resulted from severe craniocerebral trauma, 8 patients with hypophysoma, 5 with glioma and 3 with meningeoma were chosen in our study; CT three-dimensional reconstruction of their imaging data were performed and used for preoperative planning before surgery assisted by neurosurgical station.According to CT three-dimensional reconstruction results, appropriate neurosurgical approach was planned and patients were treated by surgery. Results Neurosurgical station performed three-dimensional reconstruction could show three-dimensional quantitative relationship between the above lesions and anatomical landmarks directly,which could help direct positioning and designing the best-individualized approach to improve the surgical accuracy and efficacy. Neurosurgical station could improve the efficiency of scientific research and clinical work by managing,storing,editing and using the imaging and video of the patients. Conclusion Neurosurgical station, which can show three-dimensional quantitative relationship between the above lesions and anatomical landmarks directly, is a simple, fast and accurate preoperative planning and information processing tool for clinical neurosurgical practice.
6.Role of Wnt/β-catenin signaling in aging of mesenchymal stem cells of rats.
Xiao-xia XIANG ; Lv CHEN ; Jun-hao WANG ; Yu-bin ZHANG ; Da-yong ZHANG
Journal of Zhejiang University. Medical sciences 2011;40(6):630-640
OBJECTIVETo investigate the role of Wnt/β-catenin signaling in aging of mesenchymal stem cells (MSCs) of rats.
METHODSSerum samples were collected from young (8 ≈ 12 w) and aged (64 ≈ 72 w) SD rat. Four experiment groups were assigned: young rat serum (YRS), YRS+Wnt 3a, old rat serum (ORS) and ORS+DKK1 groups. Immunofluorescence and Western blotting were used to detect the expression of intracellular β-catenin. The senescence-associated changes were examined with SA-β-galactosidase staining. The proliferation ability was tested by MTT assays. The survived and apoptotic cells were determined by AO/EB staining. The expressions of γ-H2A. X and p53 protein were detected by immunofluorescence and Western blotting. RT-PCR was used to detect the expression of p53 and p21 mRNA.
RESULTSCompared with the YRS group, the intracellular expression of β-catenin in the ORS group was significantly increased,especially in the nuclei of MSCs. After treatment of DKK1 in ORS, the γ-catenin expression was reduced. The number of SA-β-galactosidase positive MSCs was significantly higher in the YRS+Wnt 3a group than that in the YRS group (P<0.01), and the proliferative and survival ability of MSCs was significantly decreased in the YRS+Wnt 3a group. The number of SA-β-galactosidase positive MSCs in the ORS+DKK1 group was significantly decreased compared with that in ORS group (P <0.01), and the proliferative and survival ability of MSCs was significantly increased in the ORS+DKK1 group. The expression of γ-H2A.X, p53 and p21 was markedly increased in the ORS group than that in YRS group, however, after treatment with Wnt/β-catenin signaling inhibitor DKK1, the expression of γ-H2A.X, p53 and p21 was significantly decreased compared with that in the ORS group.
CONCLUSIONResults suggest that the Wnt/β-catenin signaling is activated in the MSCs cultured with ORS and excessive activation of Wnt/β-catenin signaling can promote MSCs aging. The DNA damage response and p53/p21 pathway may be main mediators of MSC aging induced by excessive activation of Wnt/β-catenin signaling.
Animals ; Cell Proliferation ; Cell Survival ; physiology ; Cells, Cultured ; Cellular Senescence ; physiology ; Mesenchymal Stromal Cells ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Suppressor Protein p53 ; metabolism ; Wnt Proteins ; metabolism ; beta Catenin ; metabolism
7.Endovascular treatment of intracranial aneurysms using coil embolization plus an Enterprise stent.
Xiang XU ; Xiao-ming SHANG ; Jian-zhong CUI ; Da-yong WANG
Chinese Medical Journal 2011;124(4):611-614
BACKGROUNDSeveral difficulties can arise from wide-neck cerebral aneurysms when treated with endovascular embolization. We aimed to investigate the effect of endovascular treatment of intracranial aneurysms using coil embolization plus an Enterprise stent.
METHODSForty patients were treated with coil embolization plus an Enterprise stent between December 2008 and June 2010.
RESULTSThe mortality of patients was 0. All stents were successfully implanted without any surgery-related complication.
CONCLUSIONThe Enterprise stent has some advantages to be selected.
Adult ; Blood Vessel Prosthesis ; Embolization, Therapeutic ; methods ; Humans ; Intracranial Aneurysm ; surgery ; therapy ; Male ; Stents
8.Synthesis and bioactivity of 2-arylimino-4-thiazolidones.
Da-yong ZHANG ; Hua XIANG ; Yun-gen XU ; Wei-yi HUA
Acta Pharmaceutica Sinica 2006;41(9):825-829
AIMTo synthesize a series of 2-arylimino-4-thiazolidone derivatives and 2-imidazolino [2,3-b]-4-thiazolidone in order to get some novel potent compounds with nitric oxide synthases (NOS) inhibitory activity.
METHODSThe target compounds were prepared by reaction of N-chloroacetyl-1,2,3,4-tetrahydroisoquinoline or N-chloroacetylphthalimide with substituted thioureas, their NOS inhibitory activity were measured.
RESULTS AND CONCLUSIONThe 15 new compounds were synthesized and most of the reaction yields were over 65%. The structures of new compounds were identified by IR, 1H NMR, MS and elemental analyses. Bioassay indicated that, most of 15 new compounds synthesized had confirmed bioactivities inhibition against NOS.
Molecular Structure ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship ; Thiazoles ; chemical synthesis ; chemistry ; pharmacology ; Thiourea ; analogs & derivatives
9.Hepatic and renal injury induced by Radix Aristolochiae or Guanxin Suhe Wan for a long-term in rats.
Hong-Xiang QIAO ; Yong-Ye LIU ; Li-Mao WU ; Lian-Da LI
China Journal of Chinese Materia Medica 2008;33(9):1044-1048
OBJECTIVETo evaluate the toxicity of Radix Aristolochiae supplied experimental evidence of rational use of drug in clinic.
METHODAfter treatment with small dose Radix Aristolochiae, Guanxin Suhe Wan (with Radix Aristolochiae) and Guanxin Suhe Wan (without Radix Aristolochiae) in different group for a long- term, respectively, the biochemical indicator of PT, ALT, AST, ALB, ALP, Crea and BUN were detected, and the kidney, liver, stomach and urinary bladder were examined by pathologic assaying.
RESULTIn Radix Aristolochiae group and Guanxin Suhe Wan (with Radix Aristolochiae) group, all of biochemical indicator were changed significantly, and hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered.
CONCLUSIONRadix Aristolochiae and Guanxin Suhe Wan (with Radix Aristolochiae) can damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity.
Animals ; Aristolochia ; chemistry ; toxicity ; Drugs, Chinese Herbal ; toxicity ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach Neoplasms ; chemically induced ; Urinary Bladder ; drug effects ; metabolism ; pathology ; Urinary Bladder Neoplasms ; chemically induced
10.Hypoxia-inducible factor-1alpha induces the epithelial-mesenchymal transition of human prostatecancer cells.
Yong LUO ; Da-lin HE ; Liang NING ; Shu-lin SHEN ; Lei LI ; Xiang LI
Chinese Medical Journal 2006;119(9):713-718
BACKGROUNDHypoxia-inducible factor-1alpha (HIF-1alpha) is a transcriptional factor that could improve the stimulation of angiogenesis and the metabolic adaptation of tumor cells to hypoxia. A recent study showed that HIF-1alpha could induce colon cancer cells epithelial-mesenchymal transition (EMT). However, no evidence indicates a similar correlation in human prostate cancer cells. This study was designed to evaluate the effect of HIF-1alpha over-expression on the EMT in human prostate cancer cells.
METHODSWe selected the appropriate cell line for HIF-1alpha induction from those EMT negative prostate cell lines through vimentin gene detection by RT-PCR. As the result, LNCaP cell line is the best one for further experiment. LNCaP cells were transfected with recombinant plasmid pcDNA3.1 (-)/HIF-1alpha and pcDNA3.1 (-) control vector by Lipofectamine 2000 system. The positive cell colonies were confirmed by indirect immunofluorescence labeling. Then Transwell polycarbonate filter was used to analyze the invasive potency. The expression of EMT associated proteins, E-cadherin and vimentin, was detected by Western blotting.
RESULTSAmong four of the EMT negative cell lines, LNCaP was the only one expressed the vimentin gene but not the associated protein. The expression level of HIF-1alpha in LNCaP/HIF-1alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. The cell numbers of LNCaP/HIF-1alpha that penetrated through the Transwell filter were higher than that of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin was up-regulated in LNCaP/HIF-1alpha, whereas the expression of E-cadherin was down-regulated.
CONCLUSIONSOver-expression of HIF-1alpha stimulates the invasion potency of human prostate carcinoma cells through EMT pathway. The expression of E-cadherin and vimentin, playing established roles in EMT, could be regulated by HIF-1alpha in human prostate cancer cell line.
Cadherins ; genetics ; Cell Line, Tumor ; Epithelial Cells ; chemistry ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; physiology ; Male ; Mesoderm ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; analysis ; Vimentin ; genetics