1.Distinct effects of different β-adrenoceptor stimulation patterns on car-diac AMP-activated protein kinase activity
Han XIAO ; Xiaowei MA ; Yongnan FU ; Youyi ZHANG ; Zhizhen Lü
Chinese Journal of Pathophysiology 2016;32(12):2177-2183
[ ABSTRACT] AIM:To investigate the cardiac AMP-activated protein kinase ( AMPK) activity and the effects of AMPK activator on cardiac structure and function in the mice with different β-adrenoceptor (β-AR) stimulation patterns . METHODS:Male BALB/c mice were subcutaneously injected with AMPK activator ( AICAR, 250 mg· kg -1 · d-1 ) or saline, and infused with β-AR agonist isoproterenol (ISO, 5 mg· kg-1· d-1) for 14 d.The cardiac functions were evalu-ated by echocardiography or hemodynamic method , and the hearts were harvested after infusion cessation immediately or 3 d later.Phosphorylated AMPK ( p-AMPK) was measured by Western blot .RESULTS:Sustained ISO infusion increased p-AMPK level.AICAR did not further increase p-AMPK but attenuated ISO-induced increase in heart weight .Sustained ISO infusion increased cardiac systolic function as indicated by left ventricular fractional shortening ( FS) and maximum rate of pressure rise (+dp/dtmax).The cardiac systolic function was not further increased by AICAR .The cardiac diastolic func-tion as indicated by left ventricular end-diastolic pressure (LVEDP) was not different in each group .In contrast, cardiac p-AMPK level was similar between the control mice and the mice with sustained ISO infusion and ceased infusion for 3 d. In this model, AICAR improved the cardiac systolic and diastolic functions , which were impaired by ISO.Moreover, the increased pattern of p-AMPK level was similar with that of heart rate upon ISO stimulation .CONCLUSION: Sustained ISO infusion increases p-AMPK.After ISO infusion cessation for 3 d, p-AMPK is decreased to the basal level .β-AR-in-duced inotropic effects should be avoided to investigate the cardioprotective role of AMPK activation in the β-AR stimulation models.
2.Pharmacokinetic comparison of two ozagrel polymorph forms in SD rats.
Zhizhen QIN ; Qianxi CHEN ; Junke SONG ; Yang Lü ; Guanhua DU
Acta Pharmaceutica Sinica 2015;50(2):218-21
To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.
3.Research on clinical application of manual therapy to tumor-related adverse reactions
Chongjie YAO ; Zhizhen LÜ ; Shuaipan ZHANG ; Lingjun KONG ; Qingguang ZHU ; Yanbin CHENG ; Min FANG ; Kaiwei ZHANG
Journal of Acupuncture and Tuina Science 2022;20(4):321-328
Objective: To analyze the clinical application of manual therapy (MT) to tumor-related adverse reactions via summarizing the research at home and abroad, in order to provide more theoretical evidence for the clinical promotion of MT. Methods: We searched 7 Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), PubMed, Excerpta Medica Database (EMBASE), Ovid and EBSCO. The publication date was between the establishment date of the database and December 31, 2020. We screened the literature according to the inclusion and exclusion criteria, and then sorted and analyzed the selected information. Results: A total of 46 papers were analyzed. Most studies focused on the adverse reactions in breast cancer patients. MT interventions demonstrated the best efficacy for fatigue, followed by pain, depression and anxiety. In different MT interventions, Tuina (Chinese therapeutic massage) was mainly adopted for fatigue, pain, anxiety, depression, and limb dysfunctions. Acupoint pressing was mainly adopted for gastrointestinal and psychological problems such as abdominal bloating, insomnia, depression and anxiety. The application of reflexotherapy was similar to that of Tuina. Conclusion: MT can alleviate various adverse reactions by effectively relieving patients' somatic symptoms and improving their psychological states and overall functions. It can be popularized as a significant non-drug therapy. Currently, however, the clinical application of MT is neither extensive nor has sufficient basic research. Consequently, we should attach importance to this application.
4.Development of a high-efficient scarless genetic modification method for Yersinia pestis
Lisheng XIAO ; Zhizhen QI ; Ruichen Lü ; Kai SONG ; Rong CHEN ; Min WANG ; Hailian WU ; Haihong ZHAO ; Yajun SONG
Military Medical Sciences 2017;41(3):209-212,221
Objective To construct a technical platform for scarless gene modification of Yersinia pestis and to study the functions of its specific genes.Methods The resistance fragment, including upstream and downstream homologous arms of targeted regions, was reamplified by asymmetric PCR.The amplicons were introduced into Y.pestis harboring plasmid pKD46.With the induction of L-arabinose,the recombinant related enzymes: Exo, Beta and Gam, were expressed to guide the homologous recombination.A donor plasmid, pKSI-1, which carried the desired modification fragment flanking by I-SceⅠ recognition sites, was introduced into Y.pestis as the second step of λ-Red recombination with the help of pREDTKI.Results and Conclusion Two mutant strains:△waaA and waaA(△9nt), were successfully constructed for Y.pestis strain 201.Scarless modification introduces no extra modification to the genome, and it is ideal for comprehensive functional genomic studies.