AIM: To investigate effects of different therapeutic methods and typical recipes on activation of ERK1/2 in Kupffer cells of rats with fatty liver.METHODS: The rat model of fatty liver was established by feeding high fat diet combinated with distillate spirit.Meanwhile Chinese medicines Shugan fang,Jianpi fang,Huoxue fang,Qushi fang,and Zonghe fang were given to treat different groups respectively.12 weeks later,the Kupffer cells were isolated from livers of control group,model group and different treatment groups by sequential in situ perfusion with collagenaseⅣ and pronase E,density gradient centrifugation,selective adherence.The expression of total ERK1/2 and phospho-ERK1/2 in Kupffer cells of control group,model group and different treatment groups were detected by Western blotting.RESULTS: The expressions of total ERK1/2 and phospho-ERK1/2 were higher in Kupffer cells from model group than those in control group(P

Activity-based protein profiling(ABPP)and affinity-based protein profiling(AfBPP)are reliable chemical proteomics techniques that exhibit significant advantages in identifying the direct acting targets of small molecule drugs and toxicants,which can help researchers understand the pharmaco-logical and toxicological mechanisms of active small molecules.This paper introduces ABPP and AfBPP technologies and summarizes the applications of this technique in drug off-target effect and target iden-tification of toxicants in recent years,such as drug off-target effect of crenolanib,BIA 10-2474,orlistat and target identification of VX,fenitrothion,acrolein.It is hoped that this review will give readers a better idea of ABPP/AfBPP and offer a line of thinking for researchers in the fields of pharmacology,toxicology and chemical biology.

Objective To observe the influences of Qingshen (Kidney-Clearing) Granules,with effects of clearing heat,resolving dampness and dispelling stasis,on expressions of Janus-activated kinase 2 (JAK2) and signal transducers and activator of transcriptions 3 (STAT3) in Janus-activated kinasesignaltransducer and activator of transcription (JAK/STAT) signaling pathway mediated by Leptin in patients with chronic renal failure (CRF)-damp-heat pattern,and investigate the mechanism of Qingshen Granules in treatment of CRF.Methods The patients with CRF-damp-heat pattern (n =68) were randomly divided into treatment group and control group (each n =34).The study was completed actually in 60 patients,and 29 in treatment group and 31 in control group.All 2 groups were given basic treatment of Western medicine,and treatment group was additionally given Qingshen Granules (thrice daily and 1 bas every time) for 12 weeks.The clinical efficacy and changes of serum creatinine (SCr),estimated glomerular filtration rate (eGFR),serum Leptin,JAK2 and STAT3 were observed in 2 groups.Results The clinical efficacy was 86.21％ (25/29) and total effective rate of TCM patterns was 82.76％ (24/29) in treatment group,and 58.06％ (18/31) and 54.84％ (17/31) in control group (P ＜0.05).After treatment,the level of SCr decreased significantly (P ＜ 0.01) and level of GFR increased significantly (P ＜ 0.01) in treatment group compared with those before treatment,which were superior to those in control group at the same term (P ＜ 0.05).After treatment,the level of Leptin,and expressions of JAK2 and STAT3 decreased significantly (P ＜ 0.01) in treatment group compared with those before treatment,which were superior to those in control group at the same term (P ＜ 0.05 or P ＜0.01).Conclusion Qingshen Granules can reduce the level of Leptin and expressions of JAK2 and STAT3,inhibit the activation of JAK/STAT signaling pathway mediated by Leptin,relieve clinical symptoms and improve kidney function in patients with CRF-damp-heat pattern.

Objective To explore the effects of nicotinamide mononucleotide （NMN） on hypertensive rats. Methods Two rat hypertension models including spontaneously hypertensive rats（SHR）and two-kidney two-clip （2K2C） rats were used to be given single, long-term or lifelong administration of NMN respectively. NMN’s effects were assessed comprehensively by monitoring survival time, blood pressure levels, and the extent of organ damage in hypertensive model rats. Results It was revealed that NMN did not exhibit protective effects in terms of lowering blood pressure levels, reducing organ damage or increasing survival time in hypertensive rats. Conclusion This study suggested that NMN did not demonstrate anti-hypertensive effects in rat hypertension models and could provide valuable insights for future clinical observation on NMN.