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.Cyclin D1 is involved in human pulmonary artery smooth muscle cells proliferation and migration induced by cigarette smoke extract.
Min XIANG ; Yong-Jian XU ; Xian-Sheng LIU ; Da-Xiong ZENG
Acta Physiologica Sinica 2010;62(2):156-162
The present study was aimed to investigate the role of cyclin D1 in human pulmonary artery smooth muscle cells (HPASMCs) proliferation and migration induced by cigarette smoke extract (CSE). The eukaryotic expression vector of antisense cyclin D1 gene (pIRES2-EGFP-ascyclin D1) was recombinated. The recombinant and empty vector were separately transfected into normal HPASMCs using liposome. Then the cells were treated with or without 5% CSE. The cells were randomly divided into six groups: control group, vector group, antisense cyclin D1 group, 5% CSE group, vector+5% CSE group and antisense cyclin D1+5% CSE group. The expressions of cyclin D1 mRNA and protein were detected by real-time fluorescence RT-PCR and Western blot, respectively. The proliferation of HPASMCs was examined by cell cycle analysis, MTT assay and proliferation cell nuclear antigen (PCNA) immunocytochemical staining. The migration of HPASMCs was measured by Transwell cell test. The results showed that the eukaryotic expression vector of antisense cyclin D1 gene was constructed and transfected into HPASMCs successfully. The cyclin D1 mRNA and protein levels in antisense cyclin D1 group were significantly lower than those in control group (P<0.05). In 5% CSE group, the cyclin D1 mRNA and protein levels were elevated significantly compared with those in control group (P<0.05), and the indicators of cell and migration in antisense cyclin D1+5% CSE group were remarkably lower than those in 5% CSE group (P<0.05). These results suggest that CSE could promote HPASMCs proliferation and migration through up-regulation of cyclin D1 expression. PIRES2-EGFP-ascyclin D1 could attenuate CSE-induced proliferation and migration of HPASMCs by suppressing the expression of cyclin D1, which implicates that cyclin D1 might be involved in the process of HPASMCs proliferation and migration stimulated by CSE.
Cell Movement
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drug effects
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Cell Proliferation
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drug effects
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Cells, Cultured
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Cyclin D1
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physiology
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Humans
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Muscle, Smooth, Vascular
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cytology
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pathology
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Myocytes, Smooth Muscle
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cytology
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pathology
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Pulmonary Artery
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cytology
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pathology
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Smoke
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adverse effects
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Tobacco
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adverse effects
7.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
8.Cigarette smoke extract promotes human pulmonary artery smooth muscle cells proliferation through protein kinase C alpha-dependent induction of cyclin D1.
Min XIANG ; Yong-Jian XU ; Xian-Sheng LIU ; Da-Xiong ZENG
Chinese Medical Journal 2010;123(24):3663-3670
BACKGROUNDExposure to cigarette smoke stimulates the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) in vivo and in vitro. However, the molecular mechanism remains unclear. This study aimed at investigating the role of signaling pathways involving protein kinase C alpha (PKCα) and cyclin D1 in the cigarette smoke extract (CSE)-induced HPASMCs proliferation.
METHODSSynchronized HPASMCs were treated with different concentrations of CSE. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting. Cell cycle was analyzed by flow cytometry with propidium iodide staining. Activation of PKCα was measured by detecting the expression of PKCα protein in the cytosolic and membrane fractions using Western blotting analysis. Small interfering RNA (siRNA) was used to knockdown PKCα and cyclin D1. The cyclin D1 mRNA was assessed by real-time RT-PCR. The PKCα and cyclin D1 protein levels were detected by Western blotting.
RESULTSLow concentrations of CSE (1% - 10%) stimulated proliferation of HPASMCs, with its maximal effect at 5%. CSE (5%) led to PKCα activation. Inhibition of PKCα activity using Gö 6976 or siRNA-mediated knockdown of PKCα significantly attenuated CSE-induced cell proliferation and G1/S transition. Cyclin D1, one of key regulators of G1/S transition, was found to be upregulated by 5% CSE at both the mRNA and protein levels. CSE-stimulated cell proliferation and G1/S transition was abolished by cyclin D1 siRNA. Moreover, Gö 6976 or PKCα siRNA significantly suppressed CSE-induced upregulation of cyclin D1 at both the mRNA and protein levels.
CONCLUSIONPKCα-cyclin D1 pathway at least partially mediates the CSE-induced proliferation in HPASMCs.
Cell Proliferation ; Cells, Cultured ; Cyclin D1 ; physiology ; G1 Phase ; Humans ; Muscle, Smooth, Vascular ; pathology ; Myocytes, Smooth Muscle ; pathology ; Protein Kinase C-alpha ; physiology ; Pulmonary Artery ; pathology ; S Phase ; Signal Transduction ; Smoke ; adverse effects ; Tobacco ; adverse effects
9.Nephrotoxicity of Radix Aristolochice and it's substitution material Radix Inulae in rats.
Hong-Xiang QIAO ; Yong-Ye LIU ; Li-Mao WU ; Lian-Da LI
China Journal of Chinese Materia Medica 2007;32(19):2048-2051
OBJECTIVETo evaluate the toxicity of Radix Aristolochiae and Radix Inulae, and to supply the toxicity experimental data that Radix Inulae supersedes Radix Aristolochiae in clinic.
METHODA long dose of Radix Aristolochice and Radix Inulae was given intragastrically to rats for six months, then drug withdrawal for a month. The hematology and biochemical indicators were measured, and the pathologic changes of kidney, liver, stomach and urinary bladder were examined.
RESULTThe rats of Radix Aristolochice showed serious toxic responses of renal tubule atrophy and necrosis, meanwhile, the levels of BUN, Cr and NAG were increased obviously. Hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered with pathologic assaying. But the rats of Radix Inulae did not.
CONCLUSIONRadix Aristolochiae could damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity. Radix Inulae could take the place of Radix Aristolochiae to use in clinic.
Acetylglucosaminidase ; urine ; Animals ; Aristolochia ; chemistry ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Female ; Inula ; chemistry ; Kidney Tubules ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Male ; Necrosis ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach ; drug effects ; pathology ; Stomach Neoplasms ; chemically induced ; Urinary Bladder ; drug effects ; pathology ; Urinary Bladder Neoplasms ; chemically induced
10.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