Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily.It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs,heavy metal anions,toxicants,and conjugates of glutathione,glucuronide and sulfate.With the advance of sequence technology,many MRP1/ABCC1 polymorphisms have been identified.Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility.In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms.In this review,we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance,toxicity,disease susceptibility and severity,prognosis prediction,and methods to select and predict functional polymorphisms.

Objective To approach the role of Kupffer cell (KC) in regulation of liver regeneration after partial hepatectomy (PH). Methods Condition medium of kupffer cells (KCCM) was prepared and the role of KCCM in promoting rat primary hepatocytes proliferation was observed by MTT method. The PH animal model was reproduced in mice and the rate of liver regeneration was measured and the expression features of TNF-?, TGF-? and TGF-?_1 were determined by immunohistochemical methods after PH with KC depletion. Results KCCM could promote primary hepatocyte proliferation significantly (A=0.746?0.06) compared with control (A=0.536?0.06, P

Genome-wide association studies ( CWAS) use high-throughout genotyping technologies to investigate the relation of hundreds of thousands of gene markers(genotype) with clinical conditions and measurable traits (phenotype). Type 2 diabetes mellitus results from the interaction of environmental factors with genetic variants. Many progresses have been acquired from GWAS. New gene regions have been discovered to be involved in the development and function of islet (3-cells, which provides new strategies for the etiology investigation, prevention, and treatment of type 2 diabetes mellitus.

One of the most promising antimalarial drugs which are widely used throughout the world is the artemisinin (ARS)and its derivatives,e.g.,artemether,arteether,and artesunate.Their true potential lies in broader anti-disease applications.The mechanism of action of these compounds appears to involve the endoperoxide bridge to produce carbon-centred free radicals.Large clinical studies did not show serious side effects,however,there is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity.Therefore,a final and definitive statement on the safety of artemisinins still cannot be made.In contrast,animal experiments at high doses shown considerable toxicity upon application of artemisinins.In the present review,the authors give a comprehensive overview on toxicity studies in cell culture and in animals (mice,rats,rabbits,dogs,and monkeys)as well as on toxicity reported in human clinical trials.The authors emphasize the current knowledge on neurotoxicity,embryotoxicity, genotoxicity,hemato-and immunotoxicity and cardiotoxicity.Rapid elimination of artemisinins after oral intake represents a relatively safe route of administration compared to delayed drug release after intra-muscular (im ) injection. There are drug-related differences, i.e., intramuscular application of artemether or arteether,but not to artesunate,which is safe and gives good profiles after im administra-tion in severe malaria.It might also be important in determining dose limitations for treatment of other diseases such as cancer.Questions about dosing regimens,safety of long-term use and possible inter-actions with existing therapies and toxicities that might be related to the treatment of tumors should be answered by appropriate clinical and preclinical studies.

Objective To Investigate the mechanism of augmenter of liver regeneration (ALR) in promoting proliferation of damaged hepatocyte. Methods The inhibitory effects of ALR on the expression of TGF-?_1 in hepatic stellate cell and Kupffer cell were studied by immunohistochemistry and Western blot. The effects of hepatic stellate cell (Ito cell) conditioned medium (ICCM+) and Kupffer cell conditioned medium (KCCM+) prepared by treatment of using augmenter of liver regeneration (ALR) on damaged hepatocytes proliferation were studied by MTT. The antagonistical role of ALR on TGF-?_1, which inhibited damaged hepatocyte proliferation was investigated by MTT determination. Results Immunoreactive positive signal of TGF-?_1 in hepatic stellate cell and Kupffer cell stimulated by ALR were decreased. Immunolabeling of TGF-?_1 in hepatic stellate cell stimulated by ALR was weakened. The proliferation of damaged hepatocytes was increased significantly by administration of ICCM and KCCM. ALR could reverse the inhibitory role of TGF-?_1 on the proliferation of damaged hepatocyte. Conclusion ALR can promote proliferation of injured hepatocyte indirectly by inhibiting expression of TGF-?_1 in hepatic stellate cell and Kupffer cell.

Translation is a fundamental step in regulation of gene expression and abnormalities in this process may lead to cancer. In eukaryotic cells, translation of mRNA is mainly regulated by many eukaryotic initiation factors ( eIFs) . EIF3 plays an impor-tant role in translational regulation, cell growth and oncogenesis. The largest subunit of eIF3, eIF3a may play a role as a regulator of mRNAs. The relationship between eIF3a and oncogenesis has been found. Moreover, the eIF3a mRNA is ubiquitously ex-pressed in different cancer cells and can modulate the cell cycle. However, some studies indicate that eIF3a could provide protec-tion against evolution into higher malignancy and reduce the re-sistance to chemotherapy . The patients of high eIF3a expression could get a better prognosis . In fact, the role of eIF3a is still un-clear in cancer cells. EIF3a may be involved in the process of tumor pathophysiology, but its regulatory role is undulatory.

Objective To explore the association between rs3758539G-803A and rs10882283 T-179G polymorphism of retinol binding protein 4 (RBP4) and rosiglitazone response in Chinese type 2 diabetes mellitus (T2DM) patients.Methods A total of 472 Chinese T2DM patients and 198 healthy subjects were enrolled to identify G-803A and T-179G genotypes using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP ).assay.Forty-two T2DM patients with different G-803A or T-179G genotypes were selected to undergo a 12-week rosiglitazone treatment (4 mg/d).Serum fasting plasma glucose (FPG),postprandial plasma glucose (PPG),fasting serum insulin (FINS),glycated hemoglobin (HbAlc),postprandial serum insulin ( PINS),triglyceride (TG),low-density lipoprotein-cholesterol ( LDL-c),and high-density lipoprotein-cholesterol (HDL-c) were determined before and after the rosiglitazone treatment.Results T2DM patients with RBP4 G-803A GG genotype showed lower TG and LDL-c concentrations compared with that in the GA +AA genotype subjects.T2DM patients with RBP4 T-179G TT genotype showed lower waist-to-hip ratio (WHR),FPG and FINS values compared with that in the TG + GG genotype individuals.Patients with GG genotype of RBP4 G-803A had an enhanced rosiglitazone efficacy on FPG and FINS compared with that in the GA + AA genotype group.Patients with RBP4 T179G TG + GG genotype showed an enhanced rosiglitazone efficacy on HbAlc level compared with that in the TT genotype group.Conclusion RBP4 G-803A and T-179G polymorphism might be associated with the development of T2DM and affect the therapeutic efficacy of rosignitazone in Chinese T2DM patients.

AIM: To investigate the mechanisms of augmenter of liver regeneration (ALR) in promoting damaged hepatocyte proliferation.METHODS: The effects of Kupffer cell condition medium (KCCM+) stimulated by ALR on damaged hepatocyte proliferation were studied by MTT. The localization of ALR binding to Kupffer cell membrane and in intact rat liver was studied by immunohistochemistry. The IL-6 expression in Kupffer cells stimulated with ALR was observed by immunohistochemistry. RESULTS: The proliferation of damaged hepatocytes stimulated with KCCM+ was increased significantly. ALR immunostaining particles in plasm of hepatocyte were found in intact liver. The rough immunostaining particles of ALR were seen on the surface of Kupffer cell membrane. Immunostaining particles of IL-6 in Kupffer cells induced by ALR increased. CONCLUSION: ALR promotes proliferation of damaged hepatocytes indirectly by stimulating Kupffer cells.

Objective To investigate the expressions of T cell immunoglobulin and mucin-domain contain-ing moleculesfamily-3(Tim-3)and CD4+ and CD8+ T cells in peripheral blood from patients with coronary heart disease (CHD). Methods 51 CHD patients were divided into two groups:stable angina pectoris group (27 patients)and acute coronary syndromes group(24 patients). Another 25 healthy subjects confirmed by coronary angiography were selected as a control group. Peripheral blood was drawn on admission. Enzyme-linked immunosor-bent assay was used to detect the concentration of Tim-3. Flow cytometry was applied to detect the expressions of CD4+and CD8+. Results As compared with the healthy control group ,the concentration of Tim-3 and the propor-tion of CD8+ in stable angina pectoris group and acute coronary syndrome group were reduced ,and those in acute coronary syndrome group were lower. The differences were statistically significant (P < 0.05). As compared with the healthy control group,the proportion of CD4+ and the ratio of CD4+/CD8+ of stable angina pectoris group and acute coronary syndrome group were increased ,while those in acute coronary syndrome group were higher. The differences were statistically significant(P<0.05). Conclusions At the onset of CHD,the concentration of Tim-3 and the proportion of CD8+ in peripheral blood are reduced ,but the proportion of CD4+ is increased. The more severe the disease,the greater changes the values.

Translation control in eukaryotes contributes significantly to gene expression regulation during cellular processes,which enables rapid changes of specific proteins to maintain cellular homeostasis.Eukaryotic translation is a multiple-step process that comprised of four phases:initiation,elongation,termination and ribosome recycling.The initiation phase is rate-limiting and orchestrated by a set of eukaryotic translation initiation factors (eIFs).Defects in translation initiation can result in a series of diseases.Among all eIFs,eIF3 is the largest and less-known initiation factor due to its intrinsic complexity.Aberration in eIF3A,the largest subunit of eIF3,is known to contribute to carcinogenesis and protection against evolution into higher-grade malignancy,and the altered expression or mutation of eIF3A affects the responses of cancer patients to platinum-based chemotherapy.Besides its role in cancinogenesis,eIF3A is also implicated in fibrosis,and the agents inhibiting eIF3A delay the progression of this disorder.The dual roles of eIF3A in tumorigenesis are probably due to the regulation of translation of different mRNAs at different stages of tumor progression by eIF3A.In tum the encoded products serve as pro-tumor or anti-tumor proteins at different stages.