Regulation of the activity of CYP450 has always been research focus of drug metabolism. The effect of compounds on the mRNA and protein expression level of CYP450 is the main purpose of most of the existing reports. In recent years, the protein modification in the posttranslation level has been found to participate in maintaining the proper function of CYP450, thus effect of posttranslational modification on the enzyme activity has been paid more and more attention. Posttranslational modifications including phosphorylation, nitration, and ubiquitination have been described to regulate the activity of CYP450. In this paper, recent developments in the effects of posttranslational modifications on the activity of CYP450 have been reviewed.

Bone Neoplasms ; Chondroblastoma ; Humans ; Ribs ; pathology

Obstructive sleep apnea (OSA)is a high incidence of potentially dangerous disease,characterized by intermittent hypoxia or hypercapnia.It is an independent risk factor for ischemic stroke.Currently a number of studies have confirmed OSA closely associated with oxidative stress.In this paper,the complex mechanisms of oxidative stress in the OSA and the occurrence of stroke will be reviewed,such as promoting atherosclerosis,damaging the mitochondria,ischemia -reperfusion injury,ischemic preconditioning.To investigate the relationship between OSA,oxidative stress and stroke from molecular mechanisms.

Objective To investigate the effects of WNK3 kinase on the regulation of large-conductance calcium-activated potassium channels (Maxi K channels) on African green monkey kidney fibroblast-like cells (Cos-7 cells) and its mechanisms.Methods (1) Cos-7 cells were transfected with 0,0.6,1.2,1.8 μg WNK3 plasmid+0.5 μg Maxi K plasmid.The total protein expression of Maxi K channel and the phosphorylation of mitogen-activated protein kinase (MAPK) extracellular regulated kinase-1 and-2 (ERK1/2) were detected by Western blotting.(2) Cos-7 cells were divided into the control group (2.5 μg Maxi K plasmid) and the experimental group (2.5 μg WNK3 plasmid+2.5 μg Maxi K plasmid).Cell surface biotinylation was used to investigate the cell surface protein expression of Maxi K channel in Cos-7 cells.Immunoprecipitation and Western blotting were used to detect the ubiquitination of Maxi K channel protein.(3) WNK3 kinase was knocked down by WNK3 siRNA.The lysosomal degradation pathway was blocked by the proton pump inhibitor (Baf-A1).Cos-7 cells were divided into Maxi K+negative control siRNA group,Maxi K+WNK3 siRNA group and Maxi K+WNK3 siRNA+Baf-A1 group.The protein expression of Maxi K channel protein was detected by Western blotting.Results (1) Compared with those in 0 μg WNK3 plasmid groups,in 0.6,1.2,1.8 μg WNK3 plasmid groups the total protein expression of the Maxi K channel increased and the phosphorylation level of MAPK ERK1/2 reduced on a dose-dependent manner (all P ＜ 0.01).(2)Compared with those in the control group,the total protein expression and cell surface membrane protein expression of the Maxi K channel increased in the experimental group (P ＜ 0.01),while the ubiquitination of the Maxi K channel protein reduced (P ＜ 0.01).(3) Compared with the Maxi K +negative control siRNA group,the expression of Maxi K protein reduced in the Maxi K+WNK3 siRNA group (P ＜ 0.01),but did not change in the Maxi K+WNK3 siRNA + Bar-A1 group (P ＞ 0.05).The expression of Maxi K protein in Maxi K+WNK3 siRNA+Baf-A1 group was higher than that in Maxi K+WNK3 siRNA group (P ＜ 0.01).Conclusions WNK3 kinase inhibits the lysosomal degradation pathway of Maxi K channel protein by reducing the ubiquitination of Maxi K channel,and promotes the expression of Maxi K channel protein in cells and on cell membrane.These effects may be achieved by suppressing MAPK ERK1/2 signal transduction pathway.

Objective This study aimed to investigate the relationship between CLPTM1L gene and lung cancer 95-D cells sensitivity to gemcitabine,and to explore its potential mechanism of action. Methods Overexpression of lentivirus against CLPTM1L gene was constructed and infected with lung cancer 95-D cells;Cells were divided into the CLPTM1L overexpression group and con-trol group;The proliferation of cells in the overexpressing and control groups after gemcitabine treatment was detected by CCK-8;The changes of CLPTM1L gene and protein were detected by real-time PCR,Western blot and immunochemiluminescence;The changes of caspase-3/7 and caspase-9 activities were detected by bioluminescence;Western blot was used to detect the changes of p-4E-BP1 protein. Results The expression of CLPTM1L gene( P =0. 036) and its protein ( P <0. 01) was significantly increased after CLPTM1L overexpressed lentivirus-infected 95 -D cells;Compared with the control group,the proliferation of CLPTM1L overex-pressing group after gemcitabine treatment was increased(P <0. 01);The activity of caspase activity showed that the activities of caspase-3/7 and caspase-9 in the CLPTM1L overexpression group were significantly lower than those in the control group(P<0. 01);The phosphorylated level of 4E-BP1 protein in the CLPTM1L overexpression group was significantly higher than that in the control group. Conclusion Overexpression of CLPTM1L can reduce the sensitivity of lung cancer cells to gemcitabine. Its mechanism may be to increase the phosphorylation level of 4E-BP1.

Objective　To determine the prevalence of human herpesvirus 8 (HHV-8) DNA in acute leukemia (AL) patients. Methods　The presence of HHV-8 DNA sequences in peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) from 50 AL patients was examined using polymerase chain reaction (PCR). Nine human hematopoietic cell lines and PBMC from 30 normal donors were also included. Results　HHV-8 DNA sequences were detected in one case of acute myelogenous leukemia (AML). The specimens from the bone marrow aspirate, peripheral blood and serum of this patient were all positive. None of the normal donors and human hematopoietic cell lines showed evidence of HHV-8 DNA. Conclusion　The results suggest that the prevalence of HHV-8 is low in AL in China.

OBJECTIVE: To observe the clinical efficacy of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period. METHODS: Ninety patients with periarthritis who met the inclusion criteria were randomly divided into a control group 1, a control group 2 and an observation group, 30 cases in each group. Warm acupuncture was applied in the control group 1 (Jianzhen (SI 9), Jianyu (LI 15), Jianliao (TE 14), etc were selected), yoga posture method was applied in the control group 2, warm acupuncture combined with yoga posture method were given in the observation group, the treatment was given once a day, 10 times as a course with 2 days between courses and continuous for 2 courses. After 2 courses of treatment, the shoulder joint pain score and shoulder function grading were used to evaluate the clinical efficacy, and the clinical efficacy was observed. RESULTS: ①The pain scores of the three groups were significantly lower after treatment (all <0.01), and scores in the observation group was better than that in the control group 1 and the control group 2 (<0.05, <0.01). There was no significant difference between the control group 1 and the control group 2 (>0.05). ②After treatment, the functional classification of shoulder joints were significantly improved in the three groups (all <0.01), and the functional classification of shoulder joint in the observation group and the control group 2 were better than that in the control group 1 (<0.01, <0.05). There was no significant difference between the observation group and the control group 2 (>0.05). ③After 2 courses of treatment, the effective rate of the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group 1 and 76.7% (23/30) in the control group 2 (both <0.05). CONCLUSION Warm acupuncture combined with yoga posture method can effectively relieve shoulder pain and improve dysfunction. The clinical comprehensive effect is better than simple acupuncture and yoga posture method.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Periarthritis ; therapy ; Posture ; Treatment Outcome ; Yoga

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.