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The development of anticancer drugs targeting AKT1 has been reported in a variety of cancers, but there are few related studies on Chinese medicinals targeting AKT1- In this study, Compound stomachache capsules (CSC) was used for inhibiting prostate cancer (PC) cells growth by targeting AKT1 in vitro and in vivo. Through mass spectrum, target prediction and bioinformatics analysis, it is found that 37 of CSC compounds have anticancer activity, and 6 compounds such as (+)-Magnoflorine, 7-hydroxycoumarin may be their main active components against prostate cancer- The results showed that CSC had significant in vitro inhibition on the growth of prostate cancer cells (P<0- 01), and the growth inhibition rate of PC3 cells reached about 35% at 80 μg/ mL- CSC also increased ROS production, and significantly promoted apoptosis (P <0- 01) and G
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In recent years, the prevalence of hyperglycemia has been increasing, and patients’ bodies have been seriously damaged. Compared with conventional Western drugs, natural products have fewer adverse reactions and delay the complications of hyperglycemia. As a valuable natural product resource, Small-leaf Kuding (SLK) contains various beneficial components for the human body. The aim of this study was to study the regulation effect of SLK extract at different doses on blood glucose metabolism in hyperglycemic mice. Lipopolysaccharide and streptozotocin were used to induce hyperglycemia in mice. Extract of SLK were administered intragastrically at low, medium, and high doses (5 g·kg
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Aim To investigate the effects of HXL130 on the proliferation, invasion and migration of prostate cancer PC3 cells and its molecular mechanism. Methods MTT assay was used to detect the effect of HXL130 on the proliferation of prostate cancer PC3 cells. Hoechst 33258 staining and flow cytometry were used to detect the effects on apoptosis and cell cycle of cancer cells. Transwell was used to detect the effects of compounds on the invasion and migration of cancer cells. Proteomic sequencing was employed to detect differentially expressed proteins (DEPs) induced by compound treatment of cancer cells. Bioinformatics was used to analyze the functions of DEPs and the related signaling pathways regulated by DEPs, and Western blot was used to verify the result. Results The survival rate of PC3 cells decreased with the increase of HXL130 concentration and treatment time. HXL130 could significantly induce cell apoptosis and block G
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Tamsulosin hydrochloride (TSH) is a selective α
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Background Natural product sanguinarine chloride (SC) can significantly alleviate liver fibrosis and acute liver injury in mice, but whether it has a protective effect on mouse liver injury caused by sodium arsenite (SA) has not been studied. Objective To verify if SC may present preventive and therapeutic effects on SA-induced liver injury in mice. Methods A total of 140 SPF male Kunming mice were randomly divided into two sub-studies, which included a prevention sub-study and a treatment sub-study. In each sub-study, a blank group (normal saline), a model group (5 mg·kg−1 SA), and a positive control group (11.375 mg·kg−1 bicyclol and 182 mg·kg−1 glutathione), as well as SC low, medium, and high dose groups (25, 50, and 100 mg·kg−1) were arranged with 10 mice in each group. In the prevention sub-study, the blank group was given normal saline, the model group was given SA, and the other groups (the SC low, medium, and high dose groups and the positive control group) were given the corresponding treatment 30 min before gavage of SA, once a day, for 28 d. In the treatment sub-study, except for the blank group which was given normal saline, the other groups were given SA for 28 d, then the model group was given normal saline, and the other groups were given the corresponding treatment every day for 28 d. After the experiment, the mice were sacrificed to evaluate selected physiological and biochemical indicators in serum and liver tissue and to observe histopathological changes after HE staining. Results In either sub-study of preventive effect or treatment effect: compared with the blank group, body weight, liver weight, liver coefficient, as well as serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), malondialdehyde (MDA), glutathione peroxidase (GSH), and superoxide dismutase (SOD) among all SC groups were not significantly different (P>0.05); but compared with the model group, the SC groups showed increased body weight (P<0.01), decreased liver weight and liver coefficient (P<0.01), reduced ALT, AST, TBIL, and MDA (P<0.05 or P<0.01), and increased GSH and SOD with (P<0.05 or P<0.01) or without significance; compared with the positive control group, no differences were found in the above indicators (P＞0.05). The result of histopathological evaluation showed that the SC groups had a clear liver lobule structure, neatly arranged hepatic cords, and less infiltration of inflammatory cells. Conclusion SC has both preventive and therapeutic effects on SA-induced liver injury in mice.
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Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.
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OBJECTIVE：To systematically evaluate therapeutic efficacy and safety of Breviscapine injection combined with routine treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD），and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from Cochrane Library ，PubMed，Embase，CBMdisc，CNKI，VIP and Wanfang database ，randomized controlled trials （RCTs）about Breviscapine injection combined with routine treatment （trial group ） versus routine treatment （control group ）in the treatment of AECOPD were collected. After literature screening and data extraction ， the qualities of literatures were evaluated with modified Jadad scale ；Meta-analysis was performed by using Rev Man 5.2 statistical software. RESULTS ：A total of 19 RCTs were included ，involving 1 930 patients. Results of Meta-analysis showed that total response rate [OR ＝2.80，95％ CI （1.96，4.01），P＜0.000 01]，FEV1[MD＝0.65，95％ CI（0.57，0.72），P＜0.000 01]， FEV1％[MD＝5.33，95％CI（0.31，10.35），P＝0.04]，FVC[MD＝0.69，95％CI（0.23，1.16），P＝0.004]， FEV1/FVC [MD ＝ 4.83，95％CI（0.98，8.67），P＝0.01]，PEF [M D＝0.95，95％CI （0.57，1.33），P＜0.001]，PaO2 [MD＝4.70，95％CI（2.02， No.81402991） + 7.37），P＜0.001]，CD3 level [MD ＝5.11，95％ CI（3.04， 7.18），P＜0.001] and CD 4+ level [MD ＝2.62，95％CI（1.78， qq.com 3.47），P＜0.001] of trial group were significantly higher than those of control group ；PaCO2 [MD＝－3.33，95％CI（－5.02， －1.65），P＜0.001]，CD8+ level [MD ＝－2.55，95％CI（－4.28，－0.82），P＜0.004]，cough relief time [MD ＝－1.93，95％CI （－2.24，－1.63），P＜0.001]，sputum remission time [MD ＝－2.19，95％CI（－2.48，－1.89），P＜0.001]，wheezing remission time [MD ＝－1.59，95％CI（－1.86，－1.32），P＜0.001] and hospital stay [MD ＝－1.73，95％CI（－2.06，－1.39），P＜0.001] of trial groups were significantly lower or shorter than those of control group ；there was no statistical significance in CD 4+/CD8+ between 2 groups [MD ＝－0.11，95％CI（－0.23，0.01），P＝0.06]. In terms of safety ，3 studies reported the occurrence of ADR ， and no serious ADR occurred. CONCLUSIONS ：Breviscapine injection can improve clinical efficacy and lung function ，enhance immunity in patients with AECOPD with good safety.
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OBJECTIVE： To systematically evaluate the effects of roflumilast on lung function of Asian patients with chronic obstructive pulmonary disease （COPD）， and to provide evidence-based reference for rational drug use in the clinic. METHODS： Retrieved from Cochrane library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， RCTs about roflumilast or roflumilast combined with routine treatment or placebo （trial group） versus routine treatment or placebo （control group） in the treatment of Asian COPD patients were collected. After literature screening， data extraction and quality evaluation with Cochrane bias risk evaluation tool， Meta-analysis was conducted by using Rev Man 5.2 software. RESULTS： Totally 6 RCTs were included， involving 1 494 patients. Meta-analysis showed that pre-bronchodilator FEV1 （pre-FEV1） [MD＝75.19， 95％CI（53.21， 97.17）， P＜0.000 01]， post-bronchodilator FEV1 （post-FEV1） [MD＝56.60， 95％CI（27.56， 85.63）， P＝0.000 1]， forced vital capacity （FVC） [MD＝43.67， 95％CI （15.91，71.43）， P＝0.002]， average flow rate of post-bronchodilator 25％-75％ of forced vital capacity （post-FEF25％-75％） [MD＝14.58， 95％CI （8.43， 20.73）， P＜0.001]， the incidence of diarrhea [RR＝5.06， 95％CI （1.26，20.27）， P＝0.02]， respiratory infection [RR＝1.94， 95％CI （1.30，2.90）， P＝0.001]， decreased appetite [RR＝7.43， 95％CI （2.94，18.79）， P＝0.001]， body weight decrease [RR＝5.46， 95％CI （2.12，14.03）， P＝0.001]， headache [RR＝7.73， 95％CI （1.42，42.16）， P＝0.02]， dizziness [RR＝3.44， 95％CI （1.28，9.27）， P＝0.01]， gastritis [RR＝5.09， 95％CI （1.49， 17.45）， P＝0.01] and anorexia [RR＝5.06， 95％CI （1.97， 13.00）， P＝0.001] in trial group were significantly higher than control group； St. George’s Respiratory Questionnaire （SGRQ） total score [MD＝－5.82， 95％CI（－7.77， －3.87）， P＜0.001]， respiratory symptom score [MD＝－1.67， 95％CI （－2.51， －0.84）， P＜0.001]， activity limited score [MD＝－1.55， 95％CI （－2.14， －0.97）， P＜0.001] and disease impact score [MD＝－2.59， 95％CI （－3.40，－1.79）， P＜0.001] of trial group were significantly lower than those of control group. CONCLUSIONS： Roflumilast can improve lung function and dyspnea in Asian COPD patients， but it can increase the risk of ADR.
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Currently, exploring the "World-class" disciplinary construction is a vital strategy in China. Since 2015, Shanghai Jiao Tong University School of Medicine started the project of establishing two distinguish teams—the academic clinicians and clinical investigators ("Two-hundred Talent" team), to fuel the development of clinical research. After two years of practice, both advantages and bottlenecks were found. The advantage contains: increasing selection rate among talent projects, increasing influential output, elevating capacity in clinical research. The bottlenecks contain: unbalanced disciplinary development, poor awareness of the importance of clinical research, lack of relevant supporting policies. In order to improve the quality of the clinical research and the two talent clinical research teams, institutional innovation, personalized supporting system, establishment of clinical research center, training of clinical research nurses are essential.
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Objective:To investigate the role of mTOR in regulation of ICOS expression in human blood regulatory T cells. Methods:Isolation of Treg cells from human PBMC using MACS beads. We detected the ICOS expression on purified Treg cells and Treg cells viability using flow cytometry in anti-CD3 plus anti-CD28 ( antibody or beads) or anti-CD3 plus ICOSL-Fc for 3 days and 7 days. CFSE labeling human PBMC cells and in vitro cultured Treg mixed, Treg contact inhibition activity was detected by flow analysis. Results:After in vitro stimulation of Treg cells in the presence of anti-CD3+anti-CD28 for 3 days, there was no significant statistic difference in viability between ICOS+(92. 00±2. 69)% and ICOS-(90. 30±3. 53)% Treg-cells. After cultured for 7 days,the decreased ICOS+ Treg cells percentage within total Treg cells from ( 40. 20 ± 1. 83 )% to ( 11. 60 ± 1. 10 )% compared with that of 3 days. Further more,the ICOS expression level between stimulated with anti-CD28 or ICOSL-Fc condition group,compared with the ICOS MFI in the condition of anti-CD3 plus anti-CD28 treatment for 3 days was (2410. 0±746. 4) obviously higher than (403. 30±74. 42), that of the group treated with anti-CD3 plus ICOSL-FC. Rapamycin could partially suppress Treg cells ICOS expression,but unaffected the Treg suppression ability. Conclusion:ICOS expression level may not important for in vitro cultured human PBMC Treg cells survival although mTOR signling is important for regulation ICOS expression on in-vitro cultured Treg cells,but the ICOS expression on Treg regulated by multiply signaling pathways. CD28 signaling is the key stimulation factor for ICOS upregulation on in-vitro cultured Treg cells compared to ICOSL signaling.