Retraction Note: LncRNA BRE-AS1 acts as a tumor suppressor factor in bladder cancer via mediating STAT3.

The article "LncRNA BRE-AS1 acts as a tumor suppressor factor in bladder cancer via mediating STAT3", by L. Zhang, B. Liu, Q.-H. Deng, J.-X. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (10): 5320-5328-DOI: 10.26355/eurrev_202005_21314-PMID: 32495865 has been retracted by the Editor in Chief for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/F4A75D571A58C9005B703B2B8C4A8E). In particular, concerns were raised about Figures 2D and 5A as the figures result to overlap with previously published papers. The paper has been identified with the "The Clear Skies Papermill Alarm". The Editorial Office has contacted the corresponding author of the article to provide a reply to the comments on PubPeer and the raw data. Still, the journal has yet to receive a reply. Therefore, considering the comments released on PubPeer and the lack of response from authors, the Editor in Chief no longer relies on the data presented and decided to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21314.

LncRNA BRE-AS1 acts as a tumor suppressor factor in bladder cancer via mediating STAT3.

OBJECTIVE: Long non-coding RNA (lncRNA) has been verified to regulate several cancers, including bladder cancer (BC). Our study aimed to elucidate the expression, function, and mechanism of lncRNA BRE-AS1 in BC. PATIENTS AND METHODS: Relative expression of lncRNA BRE-AS1 in 77 BC tissues and adjacent normal tissues was determined using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Expression of lncRNA BRE-AS1 in T24 and EJ cells was up-regulated using lentivirus transfection. Cell counting kit-8 (CCK-8) assay and colony formation assay were used to assess the proliferation of T24 and EJ cells influenced by lncRNA BRE-AS1. Also, the influence of lncRNA BRE-AS1 on cell apoptosis and cell cycle was measured using flow cytometry. Western blot was employed to explore the downstream molecules for lncRNA BRE-AS1 in BC. In vivo, xenograft formation experiment was established in nude mice to study the function of lncRNA BRE-AS1 in BC. RESULTS: LncRNA BRE-AS1 showed significantly decreased expression in BC tissues than the paired normal tissues. In vitro experiments demonstrated that over-expression of lncRNA BRE-AS1 inhibited cell proliferation but promoted cell apoptosis of EJ and T24 cells. STAT3 was determined as a target for lncRNA BRE-AS1. In vivo, up-regulation of lncRNA BRE-AS1 reduced cancer growth in nude mice bearing BC via repressing the phosphorylation of STAT3. CONCLUSIONS: LncRNA BRE-AS1 was down-regulated in BC tissues. Over-expression of lncRNA BRE-AS1 inhibited BC cell proliferation in vitro and in vivo via repressing the phosphorylation of STAT3. This might provide a new sight for the understanding of BC progression and biotherapy.

Influence of lymph node dissection in patients undergoing radical nephrectomy for non-metastatic renal cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Whether lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for non-metastatic renal carcinoma has still been controversial recently. We conducted a meta-analysis assessing oncologic outcomes of radical nephrectomy with lymph node dissection (LND) and without lymph node dissection (non-LND) in non-metastatic renal cell carcinoma (NMRCC). PATIENTS AND METHODS: A systematic review was performed until April 2018 using a comprehensive search in PubMed, EMBASE, and Cochrane Library databases to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing radical nephrectomy with LND and radical nephrectomy with non-LND for cT1-T4NxM0 tumors. Furthermore, a subgroup analysis for locally advanced renal cell carcinoma (cT3-T4NxM0) was conducted. RESULTS: Thirteen studies on patients with LND and non- LND were identified and included in the analysis. LND group did not have a significantly better survival than non-LND group for cT1-T4NxM0 tumors (HR 0.93, 95% CI 0.78-1.11, p=0.45), However, in the subgroup of locally advanced renal cell carcinoma (cT3-T4NxM0), it showed a significantly better OS rate in patients who had undergone LND compared to those without LND (HR 0.73, 95% CI 0.60-0.90; p=0.003). CONCLUSIONS: LND offers better cancer control and better long-term survival in locally advanced renal cell carcinomas (cT3-T4NxM0). This conclusion should be confirmed by a prospective randomized clinical trial.

PLZF regulates apoptosis of leukemia cells by regulating AKT/Foxo3a pathway.

OBJECTIVE: To explore the regulatory role of PLZF in the malignant phenotype of non-APL acute myeloid leukemia (AML) and its underlying mechanism. MATERIALS AND METHODS: The expression level of PLZF in AML cell lines KG-1a, HL-60, OCI-AML3, THP-1 and K562 was detected by quantitative Polymerase Chain Reaction (qPCR) and Western blot, respectively. Subsequently, THP-1 cells were divided into mock group (no treatment), scramble group (transfection with scramble shRNA) and shPLZF group (transfection with shPLZF). THP-1 cell line stably expressing shPLZF was constructed, followed by determination of its transfection efficiency by qPCR and Western blot, respectively. The proliferation and colony formation of THP-1 cells were accessed using CCK-8 (cell counting kit-8) assay and colony formation assay, respectively. The apoptotic rate in THP-1 cells was determined using flow cytometry. Protein levels of apoptosis-related genes in THP-1 cells were detected by Western blot. Finally, protein levels of AKT, Foxo3a, pAKT and pFoxo3a were detected by Western blot as well. RESULTS: Both mRNA and protein levels of PLZF were relatively high in THP-1 cells, and were selected for the following experiments. After construction of THP-1 cell line stably expressing shPLZF, proliferative rate and colony formation abilities increased in the shPLZF group compared with the mock group and the scramble group. We found a decreased apoptotic rate, downregulated Bax and upregulated Bcl-2 in the shPLZF group than those of the mock group and scramble group. Phosphorylation levels of AKT and Foxo3a increased after interference with PLZF, whereas no significant changes in total levels of AKT and Foxo3a were observed. CONCLUSIONS: PLZF inhibits the malignant phenotype of AML by regulating the AKT/Foxo3a pathway.

Effects of miR-21 on hypertensive rats through PTEN/PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effects of micro-ribonucleic acid (miR)-21 on hypertensive rats through the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MATERIALS AND METHODS: A total of 10 spontaneously hypertensive rats (SHRs) were selected as the model group. Meanwhile, 10 rats with the same age were enrolled in the normal control group. Real Time-fluorescence quantitative Polymerase Chain Reaction (qRT-PCR) was performed to detect the mRNA level of miR-21 in rats of the SHR model group and control group. The tail arterial diastolic pressure of rats in the awake and resting state was measured in both groups, respectively. Pathological sections were prepared to evaluate pathological changes in myocardial tissues. Subsequently, myocardial cells were isolated, cultured and transfected with miR-21 mimics and miR-21 inhibitor, respectively. Transfection efficiency was verified using fluorescence quantitative PCR. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was utilized to determine the apoptosis level of myocardial cells. Furthermore, the expression levels of the signaling pathway-related proteins were detected via Western blotting assay. RESULTS: Fluorescence quantitative PCR results revealed that the expression level of miR-21 was significantly higher in the SHR model group (p<0.05). The diastolic pressure increased markedly in the SHR model group when compared with that in the control group (p<0.05). Subsequent hematoxylin and eosin (HE) staining indicated apparent myocardial tissue injury in the SHR model group (p<0.05). After transfection, the results showed that miR-21 inhibitor could effectively down-regulate the expression level of miR-21 in myocardial cells (p<0.05). Meanwhile, TUNEL staining revealed that the number of apoptotic cells in the miR-21 inhibitor group was remarkably higher than that of the other two groups (p<0.05). In addition, Western blotting results manifested that the protein expression levels of PTEN, PI3K, Akt and mTOR were significantly lower in the miR-21 mimics group (p<0.05), whereas was remarkably higher in the miR-21 inhibitor group (p<0.05). CONCLUSIONS: MiR-21 is involved in regulating the pathological symptoms and myocardial cell apoptosis in hypertensive rats through the PTEN/PI3K/Akt/mTOR signaling pathway.

mir-637 inhibits the proliferation of cholangiocarcinoma cell QBC939 through interfering CTSB expression.

OBJECTIVE: To investigate the role of mir-637 on the proliferation, migration and apoptosis in human cholangiocarcinoma (CCA) cell line QBC939, and the impact of mir-637 on Cathepsin B (CTSB) expression. MATERIALS AND METHODS: Expression of mir-637 and CTSB in CCA tissues and adjacent non-tumor tissues were measured by Real-time PCR. CTSB expression in human CCA cell lines was detected with or without mir-637 exogenous overexpression through fluorescent quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method. The efficiency of lentivirus-mir-637 vector infection, and the effect of mir-637 on the proliferation, migration ability, apoptosis and cell cycle of CCA cell were detected, respectively. The possibility of mir-637 targeting CTSB was also tested by bioinformatics method, correlation analysis and molecular biology method. RESULTS: Decreased mir-637 and increased CTSB expression were observed in CCA tissue compared with adjacent non-tumor tissues. CTSB expression in mir-637 exogenously overexpressed QBC939 cells decreased compared with negative control. Mir-637 overexpression caused significant decrease of proliferation and migration ability of QBC939 cell. In addition, mir-637 overexpression induced that the cell cycle was blocked in G0/G1 phase, and cell apoptosis rate increased significantly. CONCLUSIONS: mir-637 and CTSB play an important role in the proliferation and migration of CCA cells. Mir-637 could inhibit CTSB expression significantly, which in-turn down-regulates the proliferation, migration and invasion ability of QBC939 cell, and promotes apoptosis in QBC939 cell line.

Impact of serum FGF23 levels on blood pressure of patients with chronic kidney disease.

OBJECTIVE: To investigate the impact of serum FGF23 levels on blood pressure of patients with chronic kidney disease (CKD). PATIENTS AND METHODS: 128 patients with chronic kidney disease were selected from February 2013 to January 2016. Using CKD staging method, all the patients were divided into 1 to 5 stages according to the glomerular filtration rate. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used to detect serum FGF23 levels of CKD patients and healthy control subjects. 24 h blood pressure monitoring method was used to monitor the mean arterial pressure of patients. Spearman-related analysis method was used to statistically analyze serum FGF23 level, mean arterial pressure and glomerular filtration rate. RESULTS: The serum FGF23 levels of CKD patients were significantly higher than those of the healthy control subjects (p<0.05). Also, FGF23 expression levels in serum were positively correlated with mean arterial pressure based on the results of the Spearman-related analysis. On the other hand, FGF23 expression levels in serum were negatively correlated with glomerular filtration rate. The FGF23 expression levels in serum of the patients were significantly decreased along with the decrease of mean arterial pressure. CONCLUSIONS: Serum FGF23 level is positively correlated with mean arterial pressure and negatively correlated with glomerular filtration rate. So, FGF23 has an important clinical significance that can reflect blood pressure and treatment effect of dialysis of CKD patients.

Double ventricular response in dual AV nodal pathways mimicking interpolated premature beat.

Double ventricular response in dual atrioventricular (AV) nodal pathways can result in nonreentrant supraventricular tachycardia. Since this condition was first described in 1979, around 20 cases have been reported. Here, we present the case of a patient with a confirmed diagnosis of double ventricular response in dual AV nodal pathways resembling an interpolated premature beat who underwent successful radiofrequency ablation of the slow pathway.

ARRDC3 Inhibits the Progression of Human Prostate Cancer Through ARRDC3-ITGß4 Pathway.

BACKGROUND: Arrestin domain-containing protein 3 (ARRDC3) is a member of the mammalian α-arrestins family, which has been identified as a tumor suppressor gene in human breast cancer, but its functions are still not clear in human prostate cancer (PCa). OBJECTIVE: The purpose of the present study was to investigate clinical significance, biological functions and underlying mechanisms of ARRDC3 deregulation in PCa. METHOD: Involvement of ARRDC3 deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, microarray analysis, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor progression were determined. RESULTS: Microarray analysis found that ARRDC3 low expression was significantly associated with high Gleason score in TMA, and the expression level of ARRDC3 was negatively correlated with Gleason score, metastasis and biochemical recurrence in online Taylor Dataset. As revealed by the dataset, Kaplan-Meier analyses revealed that the biochemical recurrence-free survival (BCR-free) time of PCa patients with ARRDC3 high expression was longer than those with ARRDC3 low expression. Additionally, both univariate and multivariate analyses showed that the downregulation of ARRDC3 was an independent prognostic marker for BCR-free survival of patients with PCa. In vitro studies revealed that ARRDC3 could inhibit proliferation, migration and invasion of PCa cell lines. In vivo studies proved that ARRDC3 over-expressing cells formed significantly larger tumor nodules and remarkably speeded up tumor xenografts growth compared with the controls. Moreover, immunohistochemical scores of Ki67 and MMP-9 were significantly lower than those of the control group. Finally, correlation analysis indicated that the expression of ARRDC3 was negatively correlated with ITGß4 in clinical PCa tissues and cell lines. CONCLUSION: Our data revealed that ARRDC3 can serve as a tumor suppressor to inhibit PCa progression and an independent marker to predict the risk of biochemical recurrence and metastasis after radical resection of PCa.

Further evaluation of the potential anxiolytic activity of imidazo[1,5-a][1,4]diazepin agents selective for α2/3-containing GABAA receptors.

Positive allosteric modulators of GABAA receptors transduce a host of beneficial effects including anxiolytic actions. We have recently shown that bioavailability and anxiolytic-like activity can be improved by eliminating the ester functionality in imidazo[1,5-a][1,4]diazepines. In the present series of experiments, we further substantiate the value of heterocyle replacement of the ester for potential treatment of anxiety. None of three esters was active in a Vogel conflict test in rats that detects anxiolytic drugs like diazepam. Compounds 7 and 8, ester bioisosters, were selective for alpha 2 and 3 over alpha 1-containing GABAA receptors but also had modest efficacy at GABAA alpha 5-containing receptors. Compound 7 was efficacious and potent in this anxiolytic-detecting assay without affecting non-punished responding. The efficacies of the esters and of compound 7 were predicted from their efficacies as anticonvulsants against the GABAA antagonist pentylenetetrazole (PTZ). In contrast, the related structural analog, compound 8, did not produce anxiolytic-like effects in rats despite anticonvulsant efficacy. These data thus support the following conclusions: 1) ancillary pharmacological actions of compound 8 might be responsible for its lack of anxiolytic-like efficacy despite its efficacy as an anticonvulsant 2) esters of imidazo[1,5-a][1,4]diazepines do not demonstrate anxiolytic-like effects in rats due to their low bioavailability and 3) replacement of the ester function with suitable heterocycles markedly improves bioavailability and engenders molecules with the opportunity to have potent and efficacious effects in vivo that correspond to human anxiolytic actions.

Effects of silencing annexin A5 on proliferation and invasion of human cholangiocarcinoma cell line.

OBJECTIVE: We investigated the expression of annexin A5 (ANXA5) in human cholangiocarcinoma (CCA) cell line and its effect on proliferation, migration, and apoptosis of human CCA cells. MATERIALS AND METHODS: Expression of ANXA5 was detected by fluorescent quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting method in 2 human CCA cell lines, QBC939 and RBE. 3 shRNA plasmids for ANXA5 silencing (ANXA5-sh1, ANXA5-sh2, ANXA5-sh3) and 1 negative control plasmid were constructed to infect QBC939 cells. The infection efficiency, expression of ANXA5, apoptosis and cell cycle of QBC939 cell were measured separately. RESULTS: The expression of ANXA5 in QBC939 cell was significantly higher than RBE cell. Expressed ANXA5 protein in the QBC939-KD cell (QBC939 cell treated by RNAi) was significantly lower than QBC939-BC (QBC939 cell) and QBC939-NC cells (QBC939 cell treated by scramble plasmid). The ratio of G0/1 phase cells and apoptosis rate increased in QBC939-KD cell. The proliferation activity and invasion ability decreased in QBC939-KD cell compared with QBC939-NC and QBC939-BC cells. CONCLUSIONS: ANXA5 play important role in the migration and apoptosis of CCA cells. Inhibiting the expression of ANXA5 significantly reduce the proliferation, migration and invasion ability of QBC939 cells, and increase the apoptosis of QBC939 cells.

Three Case Reports of Splenic Artery Steal Syndrome After Liver Transplantation.

Splenic artery steal syndrome (SASS) has gained attention as a complication involving the hepatic artery and can cause ischemia in a grafted liver. This article presents 3 patients with SASS, including their diagnosis and treatment. Contrast-enhanced ultrasonography and angiography are useful in diagnosing SASS, and splenic artery trunk embolization is an effective treatment. The purpose of this article is to reinforce the understanding of the development and progression of SASS.

Computed Tomography Identifies Hepatic Portal Venous Gas Caused by Severe Diarrhoea.

AIM: To use computed tomography (CT) to diagnose the reasons for hepatic portal venous gas (HPVG) in the case of an elderly male patient. METHODS: This is a case study of an elderly male patient who suffered acute, obvious abdominal pain accompanied with stop of exhaust defecation following three days of diarrhoea, abdominal distention and emesis. The patient also developed asthma, which gradually became severe. The patient was admitted to the hospital where he underwent a physical examination and a CT scan. RESULTS: The CT results confirmed that the patient was suffering from HPVG caused by severe diarrhoea. The CT scan showed obvious expansion and pneumatosis in the enteric cavity and subcutaneous emphysema in the intestinal wall. Also, the intrahepatic portal branches and small branches of veins in the mesentery were filled with a high density of gas. The combination of many factors led to HPVG. Gastrointestinal mucosa and pressure accompanied with intestinal septic infection were the main factors. The case report revealed that gas in the enteric cavity went into the submucosa, then into the small branches of veins in the mesentery and finally into the intrahepatic portal vein system. CONCLUSIONS: Computed examination revealed the imaging features of HPVG. Hepatic portal venous gas suggested the growth of enteric cavity pressure, the damage of intestinal mucosa and intestinal infection, providing references for clinical diagnosis.

The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury.

Receptor-interacting protein (RIP)3 is a critical regulator of necroptosis and has been demonstrated to be associated with various diseases, suggesting that its inhibitors are promising in the clinic. However, there have been few RIP3 inhibitors reported as yet. B-Raf(V600E) inhibitors are an important anticancer drug class for metastatic melanoma therapy. In this study, we found that 6 B-Raf inhibitors could inhibit RIP3 enzymatic activity in vitro. Among them, dabrafenib showed the most potent inhibition on RIP3, which was achieved by its ATP-competitive binding to the enzyme. Dabrafenib displayed highly selective inhibition on RIP3 over RIP1, RIP2 and RIP5. Moreover, only dabrafenib rescued cells from RIP3-mediated necroptosis induced by the necroptosis-induced combinations, that is, tumor necrosis factor (TNF)α, TNF-related apoptosis-inducing ligand or Fas ligand plus Smac mimetic and the caspase inhibitor z-VAD. Dabrafenib decreased the RIP3-mediated Ser358 phosphorylation of mixed lineage kinase domain-like protein (MLKL) and disrupted the interaction between RIP3 and MLKL. Notably, RIP3 inhibition of dabrafenib appeared to be independent of its B-Raf inhibition. Dabrafenib was further revealed to prevent acetaminophen-induced necrosis in normal human hepatocytes, which is considered to be mediated by RIP3. In acetaminophen-overdosed mouse models, dabrafenib was found to apparently ease the acetaminophen-caused liver damage. The results indicate that the anticancer B-Raf(V600E) inhibitor dabrafenib is a RIP3 inhibitor, which could serve as a sharp tool for probing the RIP3 biology and as a potential preventive or therapeutic agent for RIP3-involved necroptosis-related diseases such as acetaminophen-induced liver damage.

Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation.

Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity.

Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin(®) or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection.

Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks.

Tumor multidrug resistance (MDR) can result from overexpression of drug transporters and deregulation of cellular signaling transduction. New agents and strategies are required for overcoming MDR. Here, we report that tanshinone-1, a bioactive ingredient in traditional Chinese medicine, directly killed MDR tumor cells and their corresponding parental cells, which was potentiated by inhibition of secondary activation of signaling networks. Tanshinone-1 was slightly more potent at inducing cytotoxicity and apoptosis in MDR cells than in corresponding parental cells. Tanshinone-1-induced MDR cell killing was independent of the function and expression of drug transporters but was partially correlated with the phosphatase-dependent reduction of phospho-705-Stat3, which secondarily activated p38-, AKT-, and ERK-involved signaling networks. Cotreatments with p38, AKT, and ERK inhibitors potentiated the anti-MDR effects of tanshinone-1. Our study presents a model for MDR cell killing using a compound of natural origin. This model could lead to new therapeutic strategies for targeting signaling network(s) in MDR cancers as well as new strategies for multitarget design.

Effect of increased levels of adiponectin by administration of the adeno vector rAAV2/1-Acrp30 on glucose, lipid metabolism and ultrastructure of the aorta in Goto-Kakizaki rats with arteriosclerosis.

BACKGROUND: We used recombinant adeno-associated virus vector of adiponectin (AAV2/1-Acrp30) to study the effects of increased levels of adioponectin (by the administration of rAAV2/1-Acrp30) on arteriosclerosis, glucose and lipid metabolism in Goto-Kakizaki (GK) rats with arteriosclerosis. METHODS: Thirty GK rats with arteriosclerosis were divided into 3 equal groups: control group 1, control group 2 and the rAAV2/1-Acrp30-administered group. Saline, virus vector or rAAV2/1-Acrp30 (10 12 ng/ml) vector genomes administered to the rats in the corresponding group by intramuscular injection to the posterior limb by single administration, respectively. After 8 weeks, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum insulin, serum total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured in each group, and the ultrastructure of the aorta was seen by light and electron microscopy. RESULTS: Compared with control groups 1 and 2, in the rAAV2/1-Acrp30 group, there was a decrease in urine volume, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum total cholesterol, triglycerides and low-density lipoprotein, and an increase in body weight and high-density lipoprotein (p< 0.05), while the level of serum insulin was not changed (p>0.05). Ultrastructure studies of the aorta showed that aortosclerosis in the rAAV2/1-Acrp30-administered group was less, and fewer lipid droplet vacuoles were seen in the vascular endothelial cytoplasm. Also various cell organelles and internal elastic lamina were seen, and there was no formation of lipid droplet and foam cells in the cytoplasm of the media of the smooth muscle. CONCLUSION: Adiponectin could improve blood glucose and lipid parameters and decrease atherosclerosis in the aorta of GK rats.

Probabilistic acute dietary exposure assessment of the Chinese population to cypermethrin residues.

A probabilistic estimation of dietary exposure to cypermethrin residues for the Chinese population was performed. Cypermethrin residue data were obtained from the national food contamination monitoring program for 2001-2006, encompassing 14,096 samples from 36 commodities with a detection rate of 10.4%. Food consumption data were gathered from the national nutrition and health survey conducted in 2002, comprising 65,915 consumers aged 2-100 years and 3701 children of 2-6 years old. The whole country was roughly divided into six regions and the ranges of the median and of P99.9 exposure estimated for these regions were 0.018-0.026 and 3.131-7.095 µg kg(-1 )bw day(-1), respectively. Pak-choi and Chinese cabbage contributed 33.9 and 13.2%, respectively, to the cypermethrin intake for the general population, while pak-choi and citrus covered 30.7 and 22.5% of the total intake for children, respectively. The exposure of the rural population was higher than urban populations. Rural areas mainly located in the plains of central China had among the highest exposure of the six regions, accounting for 17.7% of the ARfD at P99.9, while the 99.99th percentile of exposure for children, especially rural children, far exceeded the ARfD, which is a cause for concern.

Effect of total flavonoid fraction of Astragalus complanatus R. Brown on angiotensin II-induced portal-vein contraction in hypertensive rats.

The objective of the present study was to examine further the underlying mechanism of the antihypertensive effect of the total flavonoid (TF), extracted from the seed of Astragalus complanatus R.Brown. Renovascular hypertension rats (RHR) were established by the two-kidney one clip (2K1C) method. The effect of TF on the contraction of portal vein was studied in an isolated preparation. The response of portal vein to angiotensin II (Ang II) was expressed as a percentage of the 100 mmol/l KCl induced maximum contraction. We took the dose-response curve of portal vein to Ang II (from 10(-9) to 10(-6) mmol/l) as the control and then observed the change of curve after TF and Valsartan (Ang II receptor blocker) administration. Ang II induced a concentration-dependent increase of the contraction amplitude (maximal increase, 46.53+/-5.15% of 100 mmol/l KCl induced contraction at Ang II 10(-6) mmol/l in RHR). The Ang II-induced portal vein contraction was prevented by TF with a concentration related manner (maximal inhibition amplitude from 46.53+/-5.15% to 22.525+/-4.67% of 100 mmol/l KCl contraction at 10(-6)mmol/l Ang II and 3.12 x 10(-1) mg/l TF in RHR). The effect of TF on Ang II-induced portal vein contraction was similar to Valsartan. These results showed that the antihypertensive action of TF was attributed to the dilation of vessels and is related to the blockade of the Ang II receptor.