BACKGROUND: Some studies have presented that vascular endothelial growth factor and its receptor system may take part in onset and development of diabetic nephropathy (DN).OBJECTIVE: To further verify the interventional effects of irbesartan on vascular endothelial growth factor (VEGF) and its Flk-1 receptor expressions in kidney of diabetes mellitus (DM) rat, and the possible mechanism of irbesartan.DESIGN: Randomized control animal study.SETTING: West China Hospital of Sichuan University.MATERIALS: Eighteen male closed colony SD rats weighing 150-200 g were cared in standardization.METHODS: This study was performed at Laboratory of West China Hospital of Sichuan University from August 2006 to April 2007. All rats were randomly divided into a DN group, an irbesartan group and a normal control group, with 6 rats in each group. 10 g/L streptozotocin (55 mg/kg) was intraperitoneally injected to establish models; rats in the control group were administrated with the same dosage of citric acid buffer solution; rats in the irbesartan group were administrated with 3 mg/(kg·d) irbesartan after model establishment. VEGF and FIk-1 expressions were detected using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry technique; while, urine protein level, area and volume of renal glomerulus were detected, and correlations of data were analyzed.MAIN OUTCOME MEASURES: ①Renal pathological indicators, urine protein level, area and volume of renal glomerulus; ②VEGF and Flk-1 expressions;③renal immunohistochemical examination;④ correlation analysis.RESULTS:① Renal pathological examination by HE staining indicated that renal glomerulus was remarkably enlarged in the DN group; mesangial matrix was increased; mesangial cells were also increased; renal tubule was expanded. The lesions in the irbesartan group were milder compared to the DN group. Urine protein level in the DN group was significantly higher compared to the control group (P ＜ 0.01); renal weight/body mass, area and volume of renal glomerulus were significantly higher compared to the control group (P ＜ 0.01); urine protein level, renal weight/body mass, area and volume of renal glomerulus in the irbesartan group were significantly lower compared to the DN group (P ＜ 0.01). ② By the 16th week,VEGF and Flk-1 expressions in the DN group were significantly up-regulated compared to control group (P ＜ 0.05); while,VEGF and Flk-1 expressions in the irbesartan group were also up-regulated compared to the control group by the 16th week (P ＜ 0.05) but down-regulated compared to the DN group (P ＜ 0.05). ③ VEGF staining in the DN group was darker compared to control group (P ＜ 0.01), while the staining in the irbesartan group was also darker compared to the control group (P ＜0.01), but the staining in the irbesartan group was lighter compared to the DN group (P ＜ 0.01). Flk-1 staining was similar to the VEGF. ④ VEGF and Flk-1 were positively correlated, with urine protein level, area and volume of renal glomerulus (P ＜0.05).CONCLUSION: VEGF and its Flk-1 receptor play important roles in DN pathogenesis. Over expressions may cause renal injury, but irbesartan (angiotensin Ⅱ receptor antagonist) has the protective effects on kidney through inhibiting abnormal expression of VEGF and Flk-1.

Undifferentiated and differentiated 3T3-L1 adipocytes were treated with 100 ng/ml tumor necrosis factor-?(TNF-?),and peroxisome proliferator-activated receptor-?2 (PPAR-?2) mRNA expression and adiponectin secretion in cultured cells were measured.The results showed that TNF-?suppressed PPAR-?2 mRNA expression and adiponeetin secretion in 3T3-L1 adipocytes (P

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; DNA Repair ; drug effects ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Genes, Lethal ; genetics ; Genes, Tumor Suppressor ; drug effects ; Genes, cdc ; drug effects ; Humans ; Mutagenesis ; Poly(ADP-ribose) Polymerase Inhibitors ; Rad52 DNA Repair and Recombination Protein ; antagonists & inhibitors ; Recombination, Genetic ; drug effects ; genetics

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications