HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

Research advances in obeticholic acid and fibrates in treatment of primary biliary cholangitis with poor response or intolerance to ursodeoxycholic acid / 临床肝胆病杂志

Poor response or intolerance to ursodeoxycholic acid may occur in the treatment of primary biliary cholangitis (PBC), and after switch to obeticholic acid or fibrates alone or in combination, poor response or intolerance is also observed in some treatment regimens. Clinical studies on obeticholic acid and fibrates will gradually solve these issues, and obeticholic acid/fibrates combined with ursodeoxycholic acid is safe and effective in PBC patients without advanced liver cirrhosis.

Efficacy and Safety of Pemafibrate and Bezafibrate in Patients with Type 2 Diabetes / 医薬品情報学

Objective: Management of low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) is important for patients with type 2 diabetes merger hyperlipidemia. Pemafibrate (PF) has different characteristics from conventional fibrates. In this study, we retrospectively compared the efficacy and safety of PF and bezafibrate (BF) in patients with type 2 diabetes merger hypertriglyceridemia.Methods: Patients who were administered PF (0.2 mg/day) or BF (400 mg/day) for 24 weeks or longer were included. Twenty patients in each group were extracted using propensity score matching (PS). PS was calculated using the patient background (before the start of administration) of PF or BF. We investigated lipid-related parameters (TG, high density lipoprotein cholesterol [HDL-C], and LDL-C) and other laboratory test parameters pre administration and 24 weeks post administration.Results: TG decreased significantly in both groups (p<0.05). However, there were no significant differences between the two groups in the TG treatment target (<150 mg/dL) achievement rate (p =1.00), TG change rate (p=0.84), and TG change amount (p=0.77). In addition, there were no significant changes in HDL-C and LDL-C in both groups. In the PF group, alanine transaminase (ALT) (p< 0.05), alkaline phosphatase (p<0.05) decreased. In the BF group, ALT (p<0.05) and γ-GTP (p<0.05) decreased. Both groups showed improvement in liver function after 24 weeks. eGFR (p<0.05) significantly decreased only BF group. There were no significant changes in renal function, creatine kinase (CK), or hemoglobin A1c (HbA1c) in either group.Conclusion: Our study suggests that there is no difference in the TG lowering effect and safety of PF and BF in type 2 diabetic patients.

Role of 20-HETE in amelioration of renal impairment by bezafibrate in mice with diabetic nephropathy / 中国药理学通报

Aim To investigate the protective effect of bezafibrate on renal injury and the changcs of 20- HETE in mice with diabetic nephropathy. Methods A diabctic model was established by long-term high-energy feeding combined with streptozotocin. The structural and functional changes of kidney were evaluated by renal pathological examination and blood urea nitrogen (BUN), serum creatinine ( Scr) , urinary albumin levels. The expressions of PPAIls and CYP4A protein were detected by Western blot. The level of 20-HETE was measured by ELISA kit. Results After four weeks with high-energy feeding, streptozotocin (40 mg • kg-1 • d"1 i. p) administration had been performed for five days. Then after seven days,fasting blood glucose (FBG) of mice exceeded 11.1 nimol • L"1, which suggested the establishment of the diabetic model. After four weeks of diabetic onset, the levels of BUN,Scr,urinary albumin increased significantly (P er and thickened basement membrane were observed in diabetic mice. Meanwhile,the expressions of PPARs and CYP4A protein in the kidney and the content of 20-HETE in serum decreased in model group (P <0. 01). With bezafibrate supplementation (75 mg • kg"' • d"1) for four weeks, both the structure and function of kidney were improved in diabetic mice,with the up-regulation of PPARs and CYP4A protein expressions and the increase of 20-HETE level (P <0. 01 ). Conclusions Bezafibrate can ameliorate renal injury in diabetic mice, which may be related to activating CYP4A-20-HETE.

Progress in the diagnosis and treatment of multiple acyl-CoA dehydrogenase deficiency / 中国实用儿科杂志

Multiple acyl-CoA dehydrogenase deficiency,also known as glutaric aciduria typeⅡ,is an autosomal recessive inherited metabolic disease. It is a mitochondrial electron transport chain and fatty acid metabolism disorder caused by a defect of electron transfer flavoprotein(ETF)or ETF dehydrogenase(ETFDH),resulting in the damage to multiple organs such as myocardia,liver,brain and skeletal muscle. The clinical diagnosis of multiple acyl-CoA dehydrogenase deficiency is difficult due to the lack of specific symptoms and signs of the patients. To make a definitive diagnosis,blood aminoacids and acylcarnitine profiles,urinary organic acids profiles and gene analysis are necessary. According to the response to ribo-flavin(or vitamin B2),multiple acyl-CoA dehydrogenase deficiency could be divided into riboflavin-responsive form and riboflavin-unresponsive form. The riboflavin-responsive form is usually observed in the late-onset cases with good outcome.The patients of riboflavin-unresponsive form usually have early-onset with severe diseases. Bezafibrate, L-carnitine,coenzyme Q10,sodium-D,L-3-hydroxybutyrate and low-fat die should be considered for the treatment. Some patients with riboflavin-unresponsive form show poor outcome.

Effects of Bezafibrate and Fenofibrate on the Proliferation of Lung Adenocarcinoma PC- 9 Cells and the Expression of c-myc / 中国药房

OBJECTIVE： To study the effects of bezafibrate （BEZ） and fenofibrate （FEN） on the proliferation of lung adenocarcinoma PC-9 cells and the expression of c-myc. METHODS： The effects of BEZ and FEN （12.5， 25， 50， 100， 200       μmol/L） on the survival rate of PC-9 cells were detected by CCK8 method. PC-9 cells were divided into administration group and control group. Administration group was given low， medium and high concentration （25， 50， 100 μmol/L） of BEZ and FEN； control group was treated with dimethyl sulfoxide for 48 h. Cell cycle distribution and apoptosis were detected by flow cytometry. qRT-PCR was used to detect mRNA relative expression of c-myc in cells. The protein relative expression of c-myc in cells were detected by Western blot assay. RESULTS： The survival rates of PC-9 cells were （80.76±3.2）％， （74.35±5.06）％， （62.8±1.23）％， （59.03±1.55）％， （39.8±1.01）％ under the action of above concentration of BEZ； and the survival rates of PC-9 cells were （74.46±1.30）％， （61.91±4.77）％， （48.95±2.8）％， （37.05±1.55）％， （32.49±1.36）％ under the action of FEN. Compared with control group， G1 phase cell ratio increased significantly in medium and high concentration groups of BEZ and FEN； the apoptotic rate of PC-9 cells was increased significantly in low， medium and high concentration groups of BEZ and FEN； mRNA and protein relative expression of c-myc were decreased significantly， with statistical significance （P＜0.05）. CONCLUSIONS： BEZ and FEN can inhibit the proliferation of PC-9 cells， and down-regulate c-myc expression.

Ursodeoxycholic acid combined with bezafibrate in the treatment of refractory primary biliary cholangitis: a meta-analysis / 中华肝脏病杂志

Objective@#To evaluate the efficacy, safety and remission rates of pruritus of bezafibrate and UDCA combination therapy in the treatment of refractory PBC.@*Methods@#PubMed, Embase, The Cochrane Library databases, Science direct, Web of Science, CBM, WangFang Data, CNKI, VIP databases were searched to collect randomized controlled trials, crossover trials and self-control clinical trials of combination therapy of UDCA and bezafibrate with UDCA monotherapy for PBC up to June, 2018. RevMan 5.3 software was used for meta-analysis. Two evaluators independently screened the literature, extracted the data, and evaluated the risk of bias of relevant study.@*Results@#Eleven studies, including 465 patients were included. Ursodeoxycholic acid combined with bezafibrate had greatly improved liver biochemical indicators (P < 0.01) and pruritus scores in patients with refractory primary biliary cholangitis (MD = -2.97, 95% CI: -4.34~ -1.60, P < 0.01). However, there was no statistically significant differences in adverse events (RR = 1.28, 95% CI: 0.96 to 1.70, P = 0.09), and mortality rate (RR = 2.58, 95% CI: 0.57 to 11.73, P = 0.22) between the two groups.@*Conclusion@#Ursodeoxycholic acid combined with bezafibrate may improve the biochemical response and pruritus score of refractory PBC, but has no significant effect on adverse events and mortality rate.

Clinical Observation of Salvianolate Combined with Bezafibrate in the Treatment Ischemic Cardiomyopa-thy / 中国药房

OBJECTIVE:To investigate the effects of salvianolate combined with bezafibrate on clinical efficacy,inflamma-tory factors and ventricular function of patients with ischemic cardiomyopathy,and the safety. METHODS:A total of 138 pa-tients with ischemic cardiomyopathy selected from our hospital during Mar. 2015-Mar. 2016 were randomly divided into observa-tion group and control group according to random number table,with 69 cases in each group. Control group was given Bezafi-brate dispersible tablets 0.2 g,po,tid. Observation group was additionally given Salvianolate for injection 200 mg added into 0.9% Sodium chloride injection 250 mL,ivgtt,qd,on the basis of control group. A treatment course lasted for 14 d,and both groups received 2 courses of treatment. Clinical efficacies,the levels of serum inflammatory factors (CRP,TNF-α,IL-6, MMP-9,MCP-1),ventricular function parameters(LVESD,LVEDD,LVEF)were compared between 2 group. The occurrence of ADR was recorded. RESULTS:Total response rate of observation group(97.10%)was significantly higher than that of con-trol group(86.96%),with statistical significance(P0.05). After treatment,the lev-els of CRP,TNF-α,IL-6,MMP-9,MCP-1,LVESD and LVEDD in 2 groups were decreased significantly,while LVEF level was decreased significantly;the improvement of observation group was more significant than that of control group,with statisti-cal significance (P<0.05). No serious ADR was found in 2 groups during treatment. CONCLUSIONS:Salvianolate combined with bezafibrate have significant therapeutic efficacy for ischemic cardiomyopathy,reduce serum inflammatory factor level and improve ventricular function with good safety.

Expression of PPARαand Acox1 in Rats with Alcoholic Fatty Liver Disease / 华中科技大学学报(医学版)

Objective To investigate the molecular biological mechanism of deposition of triglyceride(TG)in hepatocytes in alcoholic fatty liver disease(AFLD)and the pathogenesis of this condition by detecting the contents of serum tumor necrosis fac-tor-α(TNF-α),liver triglyceride(TG),peroxisome proliferator-activated receptorα(PPARα)and acyl-CoA oxidase(Acox1)mR-NAs,and liver PPARαprotein after intervention with bezafibrate,a PPARαagonist.Methods Sixty Wistar rats were randomly divided into three groups:control group(n=20),AFLD group(n=20),and bezafibrate group(n=20).Animals in control group were given distilled water by gavage once a day for 8 weeks.Those in AFLD group were given ethanol and fish oil(2.5 mL/kg) by gavage daily for the same period of time.In bezafibrate group,rats were treated by gavage with ethanol and fish oil(2.5 mL/kg)for the first 4 weeks and then with bezafibrate(100 mg/kg)for another 4 weeks.TG in the liver was measured by colorimet-ric method,serum TNF-αlevels by enzyme linked immunoabsorbent assay (ELISA),the mRNA expression of PPARαand Acox1 in hepatocytes by reverse transcription polymerase chain reaction(RT-PCR)and the expression of PPARαprotein in hep-atocytes by Western blot.Results A significant increase in TG[AFLD group(0.72±0.09)mmol/L vs.control group(0.28± 0.07)mmol/L,P<0.01]and TNF-α[AFLD group(3.01±0.31)ng/mL vs.control group(1.07±0.28)ng/mL,P<0.01]was found in AFLD group when compared with control group.After bezafibrate intervention,the contents of liver TG and serum TNF-αwere significantly decreased.The mRNA expression of PPARα[AFLD group(0.22±0.08)vs.control group(0.68± 0.13),P<0.01]and Acox1[AFLD group(0.43±0.12)vs.control group(1.14±0.21),P<0.01]was suppressed in AFLD group,which was significantly reversed by bezafibrate treatment[bezafibrate group(0.59±0.13)for PPARαmRNA vs.AFLD group,P<0.01;bezafibrate group(0.83±0.17)for Acox1 mRNA vs.AFLD group,P<0.01].The expression of PPARαpro-tein in hepatocyts was also found to decrease in AFLD group[AFLD group(0.19±0.07)vs.control group(0.48±0.11),P<0.01].After bezafibrate intervention,it was profoundly increased.Conclusion The down-expression of PPARαand Acox1 in the liver of rats with AFLD may suppress the fatty acid metabolism and lead to the TG deposition in the liver.The increase in serum TNF-αcontents also contributes to the development of AFL.Bezafibrate can prevent and treat AFL by activating PPARα,increasing the expression of PPARαand Acox1 ,promoting the metabolism of fatty acids,decreasing the TG deposition and the serum TNF-αcontents.

Therapeutic value of atorvastatin combined bezafibrate on adjusting lipid therapy in patients with acute coronary syndrome / 心血管康复医学杂志

Objective:To explore the therapeutic value of atorvastatin combined bezafibrate on adjusting lipid in pa‐tients with acute coronary syndrome (ACS) .Methods :A total of 121 ACS patients who were treated in our hospital from Apr 2013 to Sep 2013 were enrolled .According to therapeutic method ,they were divided into bezafibrate group (n=60 ,received bezafibrate treatment based on routine treatment ) and combined treatment group (n=61 , received additional atorvastatin based on treatment of bezafibrate group ) .Levels of total cholesterol (TC) ,triglyc‐eride (TG) ,low density lipoprotein cholesterol (LDL‐C) and high density lipoprotein cholesterol (HDL‐C) ,stand‐ard‐reaching rate of blood lipid and incidence rate of adverse reactions were compared between two groups before and after treatment .Results:Before treatment ,there were no significant difference in all blood lipid levels between two groups , P> 0.05. Compared with before treatment ,levels of TC ,TG and LDL‐C significantly reduced and HDL‐C level significantly rose in both groups after treatment , P0.05. Conclusion:Atorvastatin combined bezafibrate can significantly im‐prove blood lipid condition and possess good safety in ACS patients .

Suppressive effects of bezafibrate on proliferation and cytokine production by CD4+T cells from patients with primary biliary cirrhosis / 中国免疫学杂志

Objective:To investigate the effects of bezafibrate (BF) on the activation,proliferation and differentiation of CD4+T cells from primary biliary cirrhosis ( PBC) patients and to elucidate the mechanisms for the immunosuppressive effects of BF and to further provide experience basis for BF target therapy PBC.Methods:PBMCs were isolated from PBC patients then CD 4+T cells were selected by MACS, and stimulated with anti-CD3, anti-CD28, in the presence of different concentration of BF.The cytokines were measured by ELISA,and the activation,proliferation and differentiation of CD4+T cells were analyzed by flow cytometry.Results:(1) BF could inhibit the activation of CD 4+T cells in PBC patients.(2) BF could inhibit the proliferation of CD 4+T cells in PBC patients in a dose-dependent manner (P<0.05).(3)BF could down-regulation IFN-γand IL-17 production of CD4+T cells in a dose-dependent manner ( P<0.05 ).Conclusion: BF could inhibit immune responses of PBC patients by suppressing CD 4+T cells activation;proliferation and cytokine production.

The curative effects and related analysis of bezafibrate combined medroxyprogesterone acetate in the treatment of AML / 重庆医学

Objective To observe the curative effects of bezafibrate combined medroxyprogesterone acetate in the treatment of AML .Methods 40 cases of AML patients were collected and devided into experimental group (bezafibrate combined medroxypro-gesterone acetate ,6 cases) ,control group (chemotherapy ,28 cases) and non-treatment group (6 cases) ,then through a prospective analysis we studied the curative effects and related results of bezafibrate combined medroxyprogesterone acetate in the treatment of AML .Results The median survival time of the experiment group (accepted bezafibrate combined medroxyprogesterone acetate ) was 15 weeks ;the median survival time of the control group (accepted chemotherapy ) was 24 weeks ;the median survival time of the giving up group(accepted any therapy ) was 8 weeks .Conclusion Bezafibrate combined medroxyprogesterone acetate could prolong the survival time of AML patients and there were no obvious adverse reactions .

Studies on preconcentration and isolation process of bezafibrate onto different types of sorbents by the SPE.

The performed investigations are concerned on the estimation of extraction properties of copolymer styrenedivinylbenzene (SDB-1) adsorbent and four chemically bonded silica gel materials: octadecyl (C18), octyl (C8), phenyl (C6H5), cyclohexyl (C6H11) for the solid phase extraction of bezafibrate (hypolipidaemic compound) from the model solutions and river water samples. Extraction conditions such as solvent selection, their volumes and water samples pH were found to have significant influence on extraction efficiency of the studied compound. The effect of water matrix on extraction efficiency was checked too. It was found that the best extraction efficiency of bezafibrate from water sample was obtained using bonded silica-octadecyl gel sorbents and polymer material. The presence of drug in elutes was detected by spectrophotometric (measurement of absorbance at 230 nm) and HPLC-UV methods. Under optimal conditions, recoveries of the pharmaceutical were higher than 80 %. The precision of the novel extraction procedures, calculated as coefficient variation (CV %), ranged from 0.008 to 0.018 % for the all tested sorbents.

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

Impacto del tratamiento con bezafibrato en pacientes con hiperfibrinogenemia e infarto agudo del miocardio con elevación del ST / Impact of bezafibrate treatment in patients with hyperfibrinogenemia and ST-elevation acute myocardial infarction: a randomized clinical trial

Introducción: La hiperfibrinogenemia se considera predictora de eventos cardiovasculares en sujetos sanos y pacientes con cardiopatía isquémica. Como medida de prevención primaria, el bezafibrato disminuye el fibrinógeno sanguíneo y los eventos cardiovasculares, pero su efecto en el síndrome coronario agudo aún no se conoce. Material y métodos: Ensayo clínico, aleatorizado, controlado con tratamiento convencional. Se incluyeron pacientes con infarto agudo del miocardio con elevación del segmento ST y concentraciones de fibrinógeno > 500 mg/dl a las 72 horas de evolución. Se asignaron a recibir 400 mg de bezafibrato (grupo I) o tratamiento convencional (grupo II). Punto primario de evaluación: concentraciones de fibrinógeno; puntos secundarios: recurrencia de angina o infarto, falla ventricular izquierda y puntos finales combinados durante la estancia hospitalaria. Resultados: Se incluyeron 25 pacientes por grupo. Las concentraciones de fibrinógeno al egreso hospitalario fueron significativamente menores en el grupo I (532.42 ± 129.6 versus 889 ± 127.32 mg/dl del grupo II, p < 0.0001). Los puntos secundarios se presentaron con mayor frecuencia en el grupo II que en el grupo I: angina (56 versus 4%, riesgo relativo 0.071 [0.010-0.503], p < 0.0001), falla ventricular (24 versus 4%, riesgo relativo 0.167 [0.022-1.286], p = 0.049) y puntos finales combinados (76 versus 8%, riesgo relativo 0.105 [0.027- 0.405], p < 0.001). Conclusiones: El tratamiento con bezafibrato fue seguro y logró reducir el fibrinógeno en pacientes con infarto agudo. Esta reducción se asoció con menor frecuencia de eventos cardiovasculares a corto plazo.

BACKGROUND: Hyperfibrinogenemia is a predictor of cardiovascular events in healthy subjects and in patients with chronic ischemic heart disease. Bezafibrate decreases fibrinogen levels and also the incidence of major cardiovascular events in primary prevention, but its effects in acute coronary syndrome are unknown. METHODS: This is a randomized, controlled clinical trial with conventional therapy. We included patients with Acute ST Elevation Myocardial Infarction (STEAMI) and fibrinogen concentration >500 mg/dl at 72 h of evolution. We randomized subjects into two groups: bezafibrate 400 mg (group I) and conventional therapy (group II). Primary end point was decrease of fibrinogen concentrations. Secondary end points were recurrence of angina or infarction, left ventricular failure and combined end points during hospitalization. RESULTS: We included 25 patients in each group. Fibrinogen concentrations were lower at hospital discharge in Group I than in Group II (532.42 +/- 129.6 vs. 889 +/- 127.32 mg/dl in group II, p <0.0001). Secondary end points were more frequent in Group II than in Group I: angina (56% vs. 4%, RR 0.071 [0.010-0.503], p <0.0001), left ventricular failure (24% vs. 4%, RR 0.167 [0.022-1.286], p = 0.049) and combined end points (76% vs. 8%, RR 0.105 [0.027-0.405], p <0.001). CONCLUSIONS: Bezafibrate treatment was a safe treatment and reduced fibrinogen levels in patients with STEAMI and hyperfibrinogenemia. In the short term, this reduction was associated with a lower incidence of major cardiovascular events.

Activation of PPARalpha Attenuates IFNgamma and IL-1beta-induced Cell Proliferation in Astrocytes: Involvement of IL-6 Independent Pathway

The present study demonstrates the effect of fibrates, agonists of PPARalpha on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-1beta (10 ng/ml), IFNgamma (10 ng/ml), and TNF-alpha (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and 10 micrometer) reduced the IFNgamma and IL-1beta-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the IFNgamma and IL-1beta-induced cell proliferation, released IL-6 level was measured. IFNgamma and IL-1beta cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the IFNgamma and IL-1beta-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in IFNgamma and IL-1beta-stimulated astrocytes. Taken together, these results clearly suggest that activation of PPARalpha attenuates the IFNgamma and IL-1beta-induced cell proliferation through IL-6 independent pathway.

Lectin-like oxidized low density lipoprotein receptor-1 mediates effects of bezatibrate on the apoptosis of endothelial cells / 中国医师杂志

Objective To observe the influence of bezafibrate on the apoptosis and expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) mediated by oxidized low density lipoprotein(ox-LDL) in cultured human umbilical vein endothelial cells(HUVECs).Methodes The apoptosis of HUVECs mediated by ox-LDL were evaluated by flow cytometry and the expression of LOX-1 mRNA were detected by RT-PCR.Results Compared with the control group,ox-LDL could increase apoptosis and the expression of LOX-1(P<0.05),and Bezafibrate could decrease the apoptosis and the expression of LOX-1 in a concentration -dependent manner(P<0.05).Preincubation of HUVECs with polyinosinic acid for 2 hours,the apoptosis and the expression of LOX-1 decreased(P<0.05).Conclusions Bezafibrate inhibits the apoptosis of HUVECs mediated by ox-LDL by reducing the expression of LOX-1,which may be part of the reasons for bezafibrate to prevent and treat atherosclerosis.

Autoimmune Hemolytic Anemia Associated with Primary Biliary Cirrhosis / General Medicine

<b>ABSTRACT</b> : Both primary biliary cirrhosis (PBC) and autoimmune hemolytic anemia (AIHA) are uncommon diseases. Immunological dysregulation is suggested as a causative factor for both diseases. We report a 77-year-old woman who suffered from warm type AIHA complicated by PBC. Her direct antiglobulin test was positive for IgG, and negative for C3. Both anti-mitochondrial antibody and its M2 component were detected. Both alkaline phosphatase (Alp) and IgM were elevated in the serum. She was initially treated with steroids for 8 months. Her steroids were discontinued when she underwent a laparoscopic splenectomy. Ursodeoxycholic acid was discontinued due to an allergic skin reaction. Her Alp improved with bezafibrate.

Optimization of the Formulation of Bezafibrate Osmotic Pump Tablets by Central Composite Design-response Surface Methodology / 中国药房

OBJECTIVE: To prepare bezafibrate osmotic pump tablets(BOPT) and optimize its formulation by central composite design-response surface methodology(CCDRSM).METHODS: The amount of polyoxyethylene(PEO) N80 which used as an adjuvant of Bezafibrate osmotic pump tablets(A),the amount of Na2CO3(B),and the coating weight increase(C) were used as 3 factors for investigation,and the cumulative release amount at 1 h and 6 h respectively,and the linear correlation coefficient(r) of the cumulative release amount versus time were taken as indexes.The formulation of BOPT was optimized by CCDRSM and the optimized formulation was verified.RESULTS: The optimized formulation obtained was as follows: A 40 mg,B 20 mg,and C 29 mg.The tablets prepared in optimized formulation demonstrated good release behavior,with the absolute value of deviation of each index being less than 5%.CONCLUSION: The CCDRSM can be applied to optimize the formulation of BOPT and the established model is of satisfactory predictive value.

A Case of Bezafibrate induced Rhabdomyolysis / 대한내분비학회지

Bezafibrate, a fibric acid derivative related to clofibrate, is being used increasingly in the treatment of hypertriglycemia. It is relatively well tolerated at usual dosage, and has a low incidence of adverse reactions. But we had recently observed a reversible deterioration of renal function requiring hemodialysis, presumed to be caused by bezafibrate treatment in a patient with diabetic nephropathy. A 55 year old man was admitted with complaints of general weakness and painful lower extremities. He had taken bezafibrate (200 mg every 12 hours) for the previous 4 months because of hypertriglycemia. After admission, the drug was withdrawn, and he was treated conservatively management with hydration and diuretics for bezafibrate induced rhabdomyolysis. Nevertheless, his symptom was not improved, so he was taken even hemodialysis. These findings suggested that bezafibrate should be admistered with great caution to patient with renal insufficiency. When it is admistered, CK, LDH, aldolase, and sGOT levels have to be checked for early detection of potential side effect.