L-carnitine treatment of insulin resistance: A systematic review and meta-analysis.

BACKGROUND: L-carnitine has been used for several years as an adjuvant therapy in oxidative stress, blood sugar, high-sensitivity C-reactive protein (CRP), anemia, etc. However, the efficacy of L-carnitine treating insulin resistance (IR) remains controversial. Homeostasis model assessment of Insulin Resistance (HOMA-IR) is widely used in the clinical evaluation of patients with IR. OBJECTIVES: A meta-analysis, including randomized controlled trials (RCTs), was performed to assess the effect of L-carnitine on HOMA-IR patients. MATERIAL AND METHODS: The Cochrane Library, PubMed, and EMBASE databases were systematically searched to identify RCTs which evaluated the effects of L-carnitine on HOMA-IR patients. We screened relevant studies according to predefined inclusion and exclusion criteria. In the selected articles, we extracted the data: study design, sample size, age, L-carnitine dose and regimen, body mass index (BMI) of patients, mode of administration, study duration and study outcomes. RESULTS: A total of 5 studies were included for the meta-analysis. The result showed L-carnitine was useful in the treatment of IR (WMD -0.724, CI -0.959 -0.488, p < 0.0001). Evaluation at 3, 6, 9, 12 months, the p-values were 0.875, 0.165, 0.031, 0, 007, respectively. CONCLUSIONS: L-carnitine was useful in treating patients with IR. L-carnitine can treat IR more effectively with prolonging the medication time. However, more RCTs with long-term L-carnitine treatment of IR are needed to confirm the viewpoint.

Design and synthesis of novel N()-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents.

A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, 1H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.

Could Intrathymic Injection of Myelin Basic Protein Suppress Inflammatory Response After Co-culture of T Lymphocytes and BV-2 Microglia Cells?

BACKGROUND: The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells. METHODS: Totally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 µl MBP (1 mg/ml); Group B: intrathymic injection of 100 µl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1ß, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis. RESULTS: The levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45: 83.39 ± 2.56%, 82.74 ± 2.09%, 87.56 ± 2.11%; CD54: 3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-α, IL-1ß, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C. CONCLUSIONS: Intrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.

A comparison of the effects of midazolam, propofol and dexmedetomidine on the antioxidant system: A randomized trial.

Previous studies on the antioxidant activity of sedatives have predominantly been in vitro investigations that are lacking clinical data, resulting in conclusion without cogency. The aim of the present prospective, randomized study was to use single sedative drugs for anesthesia induction to compare their antioxidant properties. The effects on the antioxidant system of midazolam, propofol and dexmedetomidine were assessed using oxidative stress indicators and micronuclei (MN). Forty-nine patients undergoing esophageal cancer radical prostatectomy were selected. Midazolam, propofol and dexmedetomidine were used to induce anesthesia. Venous blood samples were obtained prior to and at 2 and at 24 h after surgery, and oxidative stress indicators were detected using the appropriate kits. The cytokinesis-block micronucleus cytome assay was executed and the frequencies of MN, nucleoplasmic bridges and nuclear buds were examined. It was found that the use of the three sedatives, respectively, led to a marked increase in the levels of free radical indicators at 2 h after surgery, which then decreased at 24 h after surgery. Furthermore, lower levels of oxidative stress were found following the use of propofol and dexmedetomidine compared with those following midazolam administration, and similar results were obtained regarding the level of MN. It is suggested that propofol and dexmedetomidine exhibit a superior antioxidant function to midazolam.

Protective effect of vitamin E on methyl methanesulfonate-induced teratozoospermia in adult Sprague-Dawley rats.

The protective effect of vitamin E (VE, α-tocopherol) on methyl methanesulfonate (MMS)-induced teratozoospermia was investigated in adult rats. Rats (n=6 per group) were divided into three groups: i) Control group, treated with distilled water from days 1 to 5; ii) the MMS group, treated with MMS at a dose of 40 mg·kg(-1) from days 1­5; or iii) the VE+MMS group, treated with MMS at a dose of 40 mg·kg(-1) from days 1­5, followed by VE at a dose of 150 mg·kg(-1) from day 6 for 6 weeks. Sperm count, motility and morphology were examined following treatment with VE. The serum testosterone level and antioxidant enzyme activity were measured, and the localization of Vasa, promyelocytic leukemia zinc finger protein (Plzf) and synaptonemal complex protein 3 (Scp3) were also examined. MMS treatment decreased sperm count and motility, and the levels of immunoreactive serum testosterone and endogenous antioxidants. In addition, MMS increased the percentage of abnormal sperm and the levels of free radicals. After MMS and VE treatment, sperm count and motility were significantly higher in rats from the VE+MMS group than in the MMS group. In addition, the serum testosterone concentration, as well as the levels of Vasa and free radicals and the percentage of abnormal sperm, decreased. The results indicated that VE has protective effects against MMS-induced teratozoospermia in adult rats.

Role of SB203580 in the regulation of human esophageal cancer cells under the effection of Diosgenin.

In order to investigate the mechanism of human esophageal Eca109 cells induced by Diosgenin (Dio), the p38 specific inhibitor SB203580 was used to inhibit the expression of p38 and Western blot was employed to detect the effect of SB203580 in Eca109 cells. MTT experiments were executed to detect the proliferation of the cells. Western blot was also applied to find the expression of phosphorylated p38 (p-p38). It is found that SB203580 can inhibit the expression of p38 in human esophageal cell Eca109. After treated with 50 µg/mL of Dio and 10 µg/mL of SB203580, the proliferation of cells showed significantly increase and the apoptosis of cells showed significantly decrease compared with the proliferation in the cells treated with Dio only. Moreover, p-p38 protein level was significantly decreased after treated by the two drugs. It is concluded that Dio may regulate esophageal Eca109 cells through p-p38 pathway.

Ternary copper(II) complexes with amino acid chains and heterocyclic bases: DNA binding, cytotoxic and cell apoptosis induction properties.

Nowadays, chemotherapy is a common means of oncology. However, it is difficult to find excellent chemotherapy drugs. Here we reported three new ternary copper(II) complexes which have potential chemotherapy characteristics with reduced Schiff base ligand and heterocyclic bases (TBHP), [Cu(phen)(TBHP)]H2O (1), [Cu(dpz)(TBHP)]H2O (2) and [Cu(dppz)(TBHP)]H2O (3) (phen=1,10-phenanthroline, dpz=dipyrido [3,2:2',3'-f]quinoxaline, dppz=dipyrido [3,2-a:2',3'-c]phenazine, H2TBHP=2-(3,5-di-tert-butyl-2-hydroxybenzylamino)-2-benzyl-acetic acid). The DNA-binding properties of the complexes were investigated by spectrometric titrations, ethidium bromide displacement experiments and viscosity measurements. The results indicated that the three complexes, especially the complex 13, can strongly bind to calf-thymus DNA (CT-DNA). The intrinsic binding constants Kb of the ternary copper(II) complexes with CT-DNA were 1.37×10(5), 1.81×10(5) and 3.21×10(5) for 1, 2 and 3 respectively. Comparative cytotoxic activities of the copper(II) complexes were also determined by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that the ternary copper(II) complexes had significant cytotoxic activity against the human lung cancer (A549), human esophageal cancer (Eca109) and human gastric cancer (SGC7901) cell lines. Cell apoptosis were detected by AnnexinV/PI flow cytometry and by Western blotting with the protein expression of p53, Bax and Bcl-2. All the three copper complexes can effectively induce apoptosis of the three human tumor cells.

Effects of the JWA gene in the regulation of human breast cancer cells.

The present study aimed to investigate whether the JWA gene can regulate the proliferation, migration and invasion of human breast cancer cells through the MAPK signaling pathway. The role of JWA in proliferation, migration, invasion and apoptosis was investigated in the MDA­MB­231 human breast cancer cell line. Following transfection with JWA­small interfering (si)RNA, the effect of JWA on apoptosis was assessed by Western blot analysis, proliferation was determined using Transwell chambers and cell migration and invasion were analyzed by transwell assay. The expression levels of extracellular signal­regulated kinase (ERK) 1/2, CSBP/RK/Mpk2 kinase (p38) and c­Jun N­terminal kinase (JNK) were detected using Western blot analysis in the siRNA and control groups. The expression of JWA in the breast cancer cells was significantly lower compared with the normal breast cells. Downregulation of JWA protein levels reduced the apoptosis and enhanced proliferation, migration and invasion of the MDA­MB­231 cells in vitro. The results of the Western blot analysis demonstrated that, compared with the control groups, the expression levels of phosphorylated (p­)p38 decreased significantly in the JWA siRNA group. No significant changes were observed in the expression levels of p­ERK1/2 or p­JNK. Therefore, the JWA gene may regulate human breast cancer cells through the MAPK signaling pathway using different types of regulation.

PKM2 gene regulates the behavior of pancreatic cancer cells via mitogen-activated protein kinase pathways.

The aim of the current study was to investigate the effect of the PKM2 gene on the proliferation, invasion, migration and apoptosis of Panc­1 and Sw1990 pancreatic cancer cells via its interaction with the mitogen­activated protein kinases (MAPKs) signaling pathways. The expression levels of PKM2 protein in pancreatic cancer cells and the corresponding normal tissues was determined with western blot analysis. Immunohistochemical analysis of PKM2 expression was carried out in paraffin­embedded sections of pancreatic cancer tissue. Two human pancreatic cancer cell lines were cultured in vitro, and a small interfering RNA (siRNA) was designed for the PKM2 gene and transfected into the cells. Cell proliferation was measured via an MTT assay, cell migration and invasion was measured via Transwell® chambers, and the effect of PKM2 on apoptosis was detected from B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein expression levels. Protein expression levels of the MAPK pathway proteins extracellular signal­regulated kinase 1/2 (ERK1/2), p38 and c­Jun N­terminal kinase (JNK) and their phosphorylated forms were measured via western blot analysis. The expression level of PKM2 was significantly upregulated in the pancreatic cancer tissue compared with that of the corresponding normal tissue. Downregulation of PKM2 expression reduced the proliferation, migration and invasion of pancreatic cancer cell lines, while increasing the levels of apoptosis. Additionally, the expression levels of the phosphorylated­(p­)ERK1/2 and p­p38 of the MAPK pathway in the PKM2 siRNA groups were markedly downregulated compared with those of the controls; however, the expression levels of ERK1/2, p38, JNK, p­p38 and p­JNK had no significantly changes compared with those of the control groups. In summary, the PKM2 gene has an important role in the proliferation, invasion, migration and apoptosis of Panc­1 and Sw1990 pancreatic cancer cells, which may be associated with the expression of ERK1/2 and p38 of the MAPK signaling cascade.

Anticancer activity and DNA-binding investigations of the Cu(II) and Ni(II) complexes with coumarin derivative.

Two new copper(II) (2) and nickel(II) (3) complexes with a new coumarin derivative have been synthesized and structurally characterized. The DNA-binding activities of the two complexes have been investigated by spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis, and viscosity measurements. The results indicate that the two complexes, especially the complex 2, can strongly bind to calf-thymus DNA (CT--DNA). The intrinsic binding constants Kb of the complexes with CT-DNA are 2.99 × 10(5) and 0.61 × 10(5) for 2 and 3, respectively. Comparative cytotoxic activities of the two complexes are also determined by MTT assay. The results show that the drugs designed here have significant cytotoxic activity against the human hepatic (HepG2), human promyelocytic leukemia (HL60), and human prostate (PC3) cell lines. Cell apoptosis was detected by Annexin V/PI flow cytometry, and the results show that the two copper complexes can induce apoptosis of the three human tumor cells. In conclusions, the two complexes show considerable cytotoxic activity against the three human cancer and induce apoptosis of the threes.

JWA gene regulates PANC-1 pancreatic cancer cell behaviors through MEK-ERK1/2 of the MAPK signaling pathway.

The present study aimed to investigate the role of JWA gene in the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells and the effect on the MAPK signaling pathway. Human PANC-1 pancreatic cancer cells were cultured in vitro, and small interfering RNA (siRNA) was designed for the JWA gene. The siRNA was transfected into PANC-1 cells. Subsequently, the cell proliferation was measured by MTT assay; cell apoptosis was detected by analyzing BAX and Bcl-2 protein expression; cell migration and invasion were measured using Transwell® chambers; and the protein expression of JWA and ERK1/2, JNK and p38 and their phosphorylated forms were measured by western blotting. By utilizing the MTT assay, the results showed that when JWA protein expression was inhibited, the proliferation of PANC-1 cells was enhanced. In addition, the expression of apoptosis-associated protein (AAP) BAX was substantially decreased, while the expression of the apoptosis inhibitor gene, Bcl-2, was significantly enhanced. Using Transwell chambers, it was found that the number of penetrating PANC-1 cells was significantly increased after transfection with JWA siRNA, suggesting that the migration and invasion of the cells was substantially increased. By studying the association between JWA and the MAPK pathway in PANC-1 cells, it was found that the expression of p-ERK1/2 of the MAPK pathway was significantly downregulated following JWA siRNA transfection. However, the expression levels of ERK1/2, JNK, p38, p-JNK and p-p38 showed no significant differences. In conclusion, it was shown that JWA affects the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells which could be attributed to effects on the expression of ERK1/2 in the MAPK pathway.

Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action.

In order to investigate the effect of a copper (II) complexes of a coumarin derivative and phenanthroline (hereinafter referred to as the coumarin-copper drug) on lung adenocarcinoma cells in vivo and in vitro, along with the mechanism of action, LA795 lung adenocarcinoma cells were treated with different concentrations of coumarin-copper drug. An MTT assay was performed to determine the cell proliferation ratio, cell apoptosis was detected by Annexin V/propidium iodide staining with flow cytometric analysis and western blot analysis was employed to evaluate the expression levels of apoptosis-associated proteins. In addition, an LA795 cell xenograft tumor model was established in nude mice, with mice receiving intraperitoneal injection once a week for three weeks of either 2 or 4 mg/kg in three divided doses coumarin­copper drug, or phosphate­buffered saline. The tumor growth curves were drawn and the tumor growth inhibition rates were calculated. The apoptotic index of subcutaneously transplanted tumor cells was determined by terminal deoxynucleotidyl­transferase­mediated dUTP nick end­labeling assay. The coumarin-copper drug effectively inhibited the proliferation of LA795 cells in a dose­ and time­dependent manner, with the half maximal inhibitory concentration equaling 2.0 µmol/l. The coumarin-copper drug also significantly induced LA795 cell apoptosis in a time-dependent manner (P<0.05), which was accompanied by upregulation p35 and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and downregulation of Bcl-2. Furthermore, the coumarin­copper drug significantly inhibited the growth of LA795 tumors in a dose dependent manner (P<0.05), in accordance with the apoptotic index. In conclusion, the coumarin-copper drug may inhibit the proliferation of LA795 cells through the induction of cell apoptosis, which may be associated with the upregulation of p53 and Bax, with concurrent downregulation of Bcl-2.

Sex-specific association between X-linked Toll-like receptor 7 with the outcomes of hepatitis C virus infection.

Toll-like receptor 7 (TLR7) senses hepatitis C virus (HCV) infection and drives the host specific innate and adaptive immune response. The aim of this study was to estimate the distributions of TLR7 single nucleotide polymorphisms (SNPs), including rs179019 and rs3853839, as well as the effect of TLR7 gene variants on TLR7 mRNA expression and cytokine production in response to TLR7 agonist in vitro. TLR7 SNP genotyping was performed among a Chinese sample population of 418 patients with persistent HCV infection, 317 patients with HCV spontaneous clearance, and 989 healthy controls. TLR7 mRNA expression and TLR7-specific IFN-α and IL-6 secretion in peripheral blood mononuclear cells, derived from 60 healthy individuals in vitro, were then quantified. We identified the association of TLR7 rs3853839C allele, haplotype CC and haplotype AC (rs179019/rs3853839) with protection against HCV persistence in Chinese females (OR=0.49, 95% CI=0.29-0.81, P=0.01 for rs3853839 GC; OR=0.29, 95% CI=0.11-0.75, P=0.01 for rs3853839 CC; OR=0.51, 95% CI=0.38-0.77, P<0.01 for haplotype CC; OR=0.29, 95% CI=0.10-0.88, P=0.03 for haplotype AC). In addition, the rs3853839 CC genotype among female carriers had significantly low TLR7 mRNA expression (P=0.006 for GG vs. CC, P=0.021 for GC vs. CC), along with decreased IFN-α (P=0.002 for GG vs. CC, P=0.021 for GC vs. CC) and increased antiviral IL-6 production (P=0.002 for GG vs. CC, P=0.030 for GC vs. CC), after treatment with Imiquimod in vitro. The cytokine profile among rs3853839 CC genotype female carriers may indicate a pronounced protective effect against persistent HCV infection. The functional polymorphism of TLR7 rs3853839C allele was found to be sex-specific and associated with protection against HCV persistence among Chinese females, which may be due to specific IFN-α and IL-6 secretion profiles.

RTN4 3'-UTR insertion/deletion polymorphism and susceptibility to non-small cell lung cancer in Chinese Han population.

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

JWA regulates human esophageal squamous cell carcinoma and human esophageal cells through different mitogen-activated protein kinase signaling pathways.

The aim of the present study was to investigate whether the JWA gene regulates the proliferation, migration and invasion of human esophageal squamous cell carcinoma (ESCC) and normal human esophageal cell lines through mitogen-activated protein kinase (MAPK) signal transduction pathways. The role of JWA in proliferation, migration, invasion and apoptosis was investigated in the Eca109 human ESCC and HET-1A normal human esophageal cell lines via transfection with JWA-small interfering (si)RNA. Western blot analysis was conducted to observe the effect of JWA on apoptosis and the regulatory effect of JWA on proliferation was determined using a thiazolyl blue tetrazolium bromide (MTT) assay. Cellular migration and invasion were analyzed via a Transwell assay. In addition, the expression levels of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK following JWA-siRNA transfection were detected by western blot analysis and compared with those of untreated cells. The downregulation of JWA protein decreased apoptosis and increased the proliferation, migration and invasion of the Eca109 and HET-1A cell lines. In the Eca109 cell line, the expression levels of phosphorylated (p)-ERK1/2 and p-JNK, but not those of p-p38, decreased significantly in the JWA siRNA group compared with those in the control groups. However, in the HET-1A cell line, JWA-siRNA transfection significantly inhibited the expression of p-p38 and demonstrated no effect on the expression levels of p-ERK1/2 and p-JNK. In conclusion, the JWA gene may regulate the ESCC and human esophageal cell lines through MAPK signaling pathways via different regulatory mechanisms.

DNA damage in peripheral blood lymphocytes from patients with OSAHS.

PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by intermittent hypoxia during sleep time, followed by oxidative stress. Hypoxia-induced oxidative stress can lead to DNA damage, which is related to chromosome aberrations and micronuclei. The purpose of this study is to investigate the level of DNA damage in peripheral blood of patients with OSAHS. METHODS: Thirty patients with OSAHS diagnosed by polysomnography and 28 healthy volunteers were assessed by the Epworth sleepiness scale. The levels of DNA damage were investigated through the cytokinesis-blocked micronucleus assay. RESULTS: In the group of patients with OSAHS, the mean frequency of binucleated cells with micronuclei were significantly higher than that in the control group (P<0.01), and the frequency of micronuclei among the patients in mild, moderate, and severe stages differed significantly (P<0.05). The mean frequency of nucleoplasmic bridge in OSAHS group was also higher than that in the control group (P<0.05). Nasal continuous positive airway pressure treatment decreased the frequencies of binucleated cells with micronuclei, nucleoplasmic bridge, and nuclear buds. CONCLUSIONS: Oxidative DNA damage increased in peripheral blood lymphocytes of OSAHS patients. It may be related to oxidative stress induced by intermittent hypoxia and may be involved in the pathogenesis of cardiovascular and other target organ injuries.

[Association between IL-10 gene polymorphisms and the outcomes of hepatitis C virus infection among high risk populations in Jiangsu province].

OBJECTIVE: To explore the relationship between interleukin (IL)-10 gene polymorphisms and the susceptibility or the outcomes of HCV infection among high-risk populations in Jiangsu province. METHODS: IL-10 gene SNPs were detected in 1555 subjects including 264 self-limited HCV infections. 371 persistent HCV infections and 920 healthy controls were selected through Taqman-MGB. RESULTS: After adjusted for cofounders as sex, age and high-risk population, data from logistic regression analysis showed that the distribution of IL-10 genotypes among the controls, spontaneous clearances and those with persistent infections did not show much differences. RESULTS: from further stratified analysis showed that, at the position of -819T/C, when compared with TT genotype, TC genotype had a significantly increasing chance of self-limited HCV infection among middle-aged, females and paid blood doners (adjusted OR values and 95%CI were: 2.160, 1.163 - 4.011; 1.693, 1.066 - 2.688 and 4.084, 1.743 - 9.570). It also had a lower risk of progressing to persistent HCV infection among those paid blood doners (the adjusted OR values and 95%CI were: 0.312, 0.130 - 0.747). CC genotype had a higher chance of self-limited HCV infection among people underwent blood dialysis (the adjusted OR values and 95%CI were: 2.120, 1.071 - 4.197). RESULTS: also showed a decreased risk of progressing to persistent infection among paid blood doners (the adjusted OR values and 95%CI were: 0.156, 0.043 - 0.566). At the position of -592A/C, when compared to AA genotype, the AC genotype had a significantly increasing chance of self-limited HCV infection among middle-aged, females and paid blood doners (the adjusted OR values and 95%CI were: 2.176, 1.173 - 4.037; 1.659, 1.055 - 2.607; 3.704, 1.625 - 8.443) but had an increased risk of persistent HCV infection among females (the adjusted OR values and 95%CI were: 1.525, 1.017 - 2.286). AC genotype showed an increased opportunity to progress to HCV persistent infection among drug users (the adjusted OR values and 95%CI were: 1.845, 1.122 - 3.034) but had a reduced risk of progressing to HCV persistent infection among paid blood doners (the adjusted OR values and 95%CI were: 0.361, 0.155 - 0.841). CC genotype had an increased opportunity to self-limited HCV infection as well as having a decreased risk of progressing to persistent infection among paid blood doners (the adjusted OR values and 95%CI were: 3.125, 1.016 - 9.605; 0.218, 0.063 - 0.748). At the position of -1082A/G, AG/GG genotypes had an increased chance of self-limited infection among blood doners (the adjusted OR values and 95%CI were: 3.780, 1.620 - 8.820). CONCLUSION: IL-10-819T/C, -592A/C, -1082A/G SNPs might be related with the susceptibility and the outcomes of HCV infection among populations at high risk.

[Influence of F protein of hepatitis C virus subtype 1b inhibits on human hepatocellular carcinoma HepG2 cell apoptosis].

OBJECTIVE: To investigate the effects of F protein of hepatitis C virus subtype 1b on the apoptosis of human hepatocellular carcinoma HepG2 cells. METHODS: HepG2 cells were transfected with recombinant plasmid pcDNA3.0-F-EGFP and pcDNA3.0-F-EGFP-HepG2 strain was exposed to Act-D and tumor necrosis factor alpha (TNF alpha) treatment in order to induce cell apoptosis with positive control pcDNA3.0-C-EGFP-HepG2, negative control pcDNA3.0-C-EGFP-HepG2 and blank control HepG2. Annexin V-FITC/PI of flow cytometry was performed to determine the number of apoptotic cells. DNA Ladder was used to observe the isolation of apoptotic DNA fragments in the apoptotic cells. RESULTS: pcDNA3.0-F-EGFP- HepG2 cell strain showed a much delayed apoptosis as well as obviously lowering the apoptotic rate when compared with the pcDNA3.0-HepG2 strain and HepG2 strain (P < 0.001). CONCLUSION: The introduction and expression of extraneous gene (the F gene of hepatitis C virus subtype 1b) could significantly inhibit the apoptosis of HepG2 cells.

The role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese population.

Insulin-like growth factors (IGFs) and their receptors play a crucial role in regulating cell proliferation, differentiation, and apoptosis. Insulin-like growth factor-binding protein-3 is the most abundant insulin-like growth factor receptor in the serum and binds the majority of insulin-like growth factors. Studies reported that circulating level of insulin-like growth factor-binding protein-3 was modulated by functional genetic variants of insulin-like growth factor-binding protein-3 and, therefore, maybe associated with the risk of gastric cancer. In this case-control study of 576 gastric cancer cases and 647 cancer-free control participants in a high-risk Chinese population, we tested the hypothesis that functional polymorphisms A-202C and Gly32Ala of insulinlike growth factor-binding protein-3 are associated with risk of gastric cancer. We found that the variant 32Ala allele was associated with a significantly increased risk of gastric cancer (adjusted odds ratio=1.84, 95% confidence interval=1.45-2.33 for 32Gly/Ala and odds ratio=2.39, 95% confidence interval=1.47-3.90 for 32Ala/Ala, respectively), compared with the wild-type homozygote 32Gly/Gly. Although the A-202C variant was not significantly associated with gastric cancer risk in the single locus analysis, we found a significant locus-locus interaction between insulin-like growth factor-binding protein-3 A-202C and Gly32Ala loci on gastric cancer risk (Pint<0.001). These findings suggest that functional variants of insulin-like growth factor-binding protein-3 might be important markers for gastric cancer susceptibility and further studies are warranted to characterize the functional relevance of the locus-locus interaction of this gene.

TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case-control analysis in a Chinese population.

PURPOSE: Transforming growth factor beta1 (TGF-beta1) and its receptor II (TGF-betaRII) are two key components of TGF-beta signaling and play an important role in carcinogenesis. Several functional polymorphisms were identified in TGFB1 and TGFBR2 and associated with elevated serum or plasma level of TGF-beta1 and enhanced transcription activity of TGFBR2. This population-based case-control study was to evaluate the contribution of functional polymorphisms in TGFB1 C-509T, Leu10Pro and TGFBR2 G-875A to the risk of esophageal squamous cell carcinoma (ESCC). METHODS: Genotyping was performed using the primer-introduced restriction analysis-PCR assay in 255 ESCC cases and 704 cancer-free controls in a Chinese population. RESULTS: The variant genotypes (-509CT/TT) of TGFB1 C-509T were associated with a 63% significantly decreased risk of ESCC (adjusted OR = 0.37, 95% CI = 0.27-0.50) compared with -509CC wild-type homozygote. In addition, a moderately decreased risk of ESCC was related to -875GA (adjusted OR = 0.70, 95% CI = 0.49-0.99) but not -875AA genotype (adjusted OR = 1.09, 95% CI = 0.51-2.35) in TGFBR2, compared with -875GG common genotype. Furthermore, subjects carrying variant genotypes either or both of TGFB1 C-509T and TGFBR2 G-875A had a significantly reduced risk of ESCC (adjusted OR = 0.37, 95% CI = 0.26-0.53 for either one variant genotype and adjusted OR = 0.30, 95% CI = 0.19-0.48 for both variant genotypes) in a dose-response manner (chi (trend) (2) = 33.87, P < 0.001) compared with subjects with both wild-type genotypes. CONCLUSIONS: These results are consistent with our previous findings in gastric cancer and support the hypothesis that genetic variants in TGFB1 and TGFBR2 may modulate the risk of ESCC.