THE ANTITUMOR ACTIVITY OF ROSCOVITINE WAS TESTED IN FOUR CERVICAL CARCINOMA CELLS: C33A, HCE-1, HeLa, and SiHa. The effects of roscovitine on ATP Lite assay, cell cycle, and apoptosis were assessed. The Sub-G1 DNA content occurred great increasing, and this indicates that apoptosis was induced quickly in HeLa cells, but slowly in the other cells. The morphological observation results showed that roscovitine induced apoptosis and cell death in the cervical carcinoma cells. Results revealed that roscovitine exhibited selective cytotoxicity towards 4 cervical carcinoma cells, and the cells showed different morphologic and apoptotic changes at the same concentration. It was estimated that cervical carcinoma cells responded differently to roscovitine because of differences in apoptotic and genetic background in different cervical carcinoma cells. This study suggested that roscovitine had the potential to be a chemotherapeutic agent against cervical carcinoma.
// Jianhui Wu 1, * , Haimei Zhu 1, * , Guodong Yang 1 , Yuji Wang 1 , Yaonan Wang 1 , Shurui Zhao 1 , Ming Zhao 1, 2 and Shiqi Peng 1 1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, PR China 2 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Ming Zhao, email: mingzhao@bjmu.edu.cn Shiqi Peng, email: sqpeng@bjmu.edu.cn Keywords: deep vein thrombosis, P-selectin, GPIIb/IIIa, cytokines, inflammation Received: June 14, 2017 Accepted: August 04, 2017 Published: August 24, 2017 ABSTRACT Deep vein thrombosis (DVT) associates with considerable morbidity, functional disability and mortality. Due to the lack of suitable inhibitor the correlation of various factors in DVT onset remains unknown. In this context we analyzed the structure of anti-platelet aggregation agent, P-selectin down-regulator, GPIIb/IIIa down-regulator and anti-inflammatory agent, thereby designed N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)- Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) as an inhibitor of DVT to receive evaluations. The docking predicted that IQCA-TAVV can target P-selectin and GPIIb/IIIa. The UV showed that IQCA-TAVV can act on P-selectin and GPIIb/IIIa. ELISA indicated that IQCA-TAVV concentration dependently inhibited activated platelets to express P-selectin and GPIIb/IIIa, and the minimal effective concentration was 1 nM. IC 50 of IQCA-TAVV against platelet aggregation induced by arachidonic acid, adenosine diphosphate and platelet activating factor fell within a range of 0.13 nM to 0.30 nM. In vivo IQCA-TAVV dose-dependently inhibited venous thrombosis and the minimal effective dose was 1 nmol/kg. On ear edema model the anti-inflammation activity of 10 nmol/kg IQCA-TAVV equaled that of 1.1mmol/kg aspirin. The concentration of IL-2, IL-6 and IL-8 in the serum of the ear edema mice were also significantly decreased by 10 nmol/kg IQCA-TAVV. Even at 1 μmol/kg of dose IQCA-TAVV still did not injure the kidney, the liver, and the nerves of healthy mice. Thereby IQCA-TAVV depicts a relationship of three levels (inhibiting platelet activation, targeting externalized membrane receptor, decreasing serum inflammatory factor) for the down-regulation of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 in DVT.
Current clinically used chemotherapeutic platinum drugs can trigger severe toxic effects. To develop a model system for the evaluation of the therapeutic efficacy and the toxic effects of new platinum agents, we have synthesized a new compound N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxylhex-1-yl]-L-hydroxyproline dichloroplatinum(II) (PHDP), compared its in vitro anti-proliferation activity, in vivo anti-tumor activity and safety to those of oxaliplatin, and correlated all these biological actions with the platinum occurring in the spleen, kidney, heart, brain, blood, tumor tissue, urine and faeces of the treated mice. We explored the atomic absorption based determinations of the platinum which occurred in the spleen, kidney, heart, brain, blood, tumor tissue, urine and faeces and constitute a model system that can be generally used in the investigation of the novel platinum agents.
Tissue-type plasminogen activator (t-PA) is currently the only approved drug by the US FDA for treating the acute ischemic stroke within 3 hours of symptom onset, despite the fact that the therapy may cause serious hemorrhagic transformations and neurotoxicity that leads to enhanced brain injury. Here we developed a synthesized small pseudopeptide, PAK01, to address efficacy and safety issues observed in t-PA treatment in acute ischemic stroke by covalently combining a free radical scavenger, a thrombus-targeted platelet aggregation inhibitor and a non-t-PA thrombolytic peptide into a single structure. The thrombolytic activity induced by PAK01 was confirmed in murine in situ thromboembolic stroke model where mice were anesthetized before thrombin is injected into middle cerebral artery to produce the clot formation (as described by Orset et al .). To induce reperfusion, PAK01 (7.5 mg/kg) or t-PA (10 mg/kg) was administered intravenously 20 minutes after thrombin injection. The results showed that both PAK01 and t-PA promote reperfusion in mice with middle cerebral artery in situ thromboembolic occlusion. Furthermore, PAK01 yields better treatment results in reducing infarct volume and neurological deficit with lower risk of hemorrhagic transformation when compared to that of t-PA. In addition, rattus carotid artery thrombosis model where 1.4 mg/kg of PAK01 was intravenously administered 4, 6, and 24 hours after stroke onset showed improvements in neuronal behavior outcome and reductions of brain infarct size. In contrast to 3 mg/kg of t-PA, no bleeding was observed even in 7 mg/kg of PAK01-treated animals. HPLC-FT/MS monitoring indicated that PAK01 can cross blood cerebral barrier. A distinct action mechanism out of plasminogen pathway was also explored. In conclusion, based on a new action mechanism the treatment potential of PAK01, a small molecule, in acute ischemic stroke through enhancing reperfusion and neuroprotection, as well as avoiding hemorrhagic transformation was demonstrated in in vivo studies.
Abstract The reactions of sulphur with phosphine and phosphite were investigated by low‐energy electron impact mass spectrometry and fast atom bombardment mass spectrometry. A previously reported mechanism of the Ph 3 P–S 8 reaction was supported and a possible mechanism for the (PhO) 3 P–S 8 reaction is proposed.
objective To understand mycoplasma and chlamydia trachomat is infections in persons with urogenital infections visiting our STD clinics Methods The urethral(or cervical)specimens were tested for u reaplasma urealyticum(UU)and Mh by culture,and chlamydia trachomatis( CT)by clear-view chlamydia rapid a ssay Results UU positive rates(3 8 65%)were higher than Mh(8 55%) The positive rates of UU+Mh and CT wer e 6 64% and 11 09% The female positive rates of UU Mh and UU+ Mh were 55.47%, 14.82% and 10.99%. which wer e higher than 28 23%, 4 74% and 4 00% is male,respectively The female posit ive rate of CT was 13 21%,the male one-9 86% In dual infections of th e chlamydia and mycoplasma,the pos itive rates of CT+UU and CT+Mh wer e 5 97% and 1 29% respectively. The triple positi ve rate of CT+UU+Mh was 0 93% Conc lusions In the middle part of Hebe i province,UU,Mh and CT positive r ates in patients with urogenital i nfections were 38 65%,8 55% and 11 09% respectively in our STD clinics
There is a correlation between tumor and inflammation. The activity of 13-[CH2CO-Cys(Bzl)-OBzl]-berberine (13-Cys-BBR) slowing tumor growth is higher than that of BBR. Whether the anti-inflammation activity of 13-Cys-BBR is higher than that of BBR remains unknown. There is a correlation between thrombosis and inflammation. Whether 13-Cys-BBR is an inhibitor of thrombosis remains unknown.The object of this investigation is to compare the activities of 13-Cys-BBR inhibiting thrombosis and inflammation to those of BBR.In vivo anti-thrombosis assay was performed on rat model of arterial and venous thrombosis. In vivo anti-inflammation assay was performed on mouse model of xylene induced ear edema.At oral dose of 66.7 nmol/kg, 13-Cys-BBR, but not BBR, inhibited the rats to form both venous thrombus and arterial thrombus. At oral dose of 2 μmol/kg, 13-Cys-BBR, but not BBR, inhibited the ears of the mice to occur edema.The anti-venous thrombosis activity, anti-arterial thrombosis activity and anti-inflammation activity of 13-Cys-BBR were significantly higher than those of BBR. 13-Cys-BBR is a promising preclinical candidate.
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