Li-hong Liu

The Effect of CHEK2 Variant I157T on Cancer Susceptibility: Evidence from a Meta-Analysis

Cell cycle checkpoint kinase 2 (CHEK2) is a checkpoint kinase that plays an important role in the DNA damage signaling network. Numerous epidemiological studies have evaluated the association between the CHEK2 I157T variant and cancer susceptibility. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CHEK2 I157T variant is associated with cancer susceptibility. PubMed, Embase (before 2012-10-1), Google Scholar, and CBMdisc were searched for studies on the relationship of the CHEK2 I157T variant and the incidence of cancer. Eligible articles were included for data extraction. The main outcome was the frequency of CHEK2 I157T polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. In total, 26,336 cases and 44,219 controls from 18 case-control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19-1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42-1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24-2.26, p=0.0008). We also found an association of the CHEK2 I157T variant with familial cases (OR=1.85, 95% CI=1.51-2.26, p<0.00001). However, the association was not established for other types of cancer (OR=1.09, 95% CI=0.75-1.57, p=0.66). This meta-analysis demonstrates that the CHEK2 I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.

Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity

The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.

Association between co-stimulatory molecule gene polymorphism and acute rejection of allograft

Co-stimulatory molecules play important roles in T cell-mediated immune response and transplantation. Numerous epidemiological studies have evaluated the association between CD28, CTLA-4 gene variant and allograft rejection. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CD28 IVS3 +17T/C variant, CTLA-4, CD86 and PDCD1 gene polymorphisms were associated with allograft rejection susceptibility. PubMed and Embase (before 2014-3-25), were searched for studies on the relationship of CD28, CTLA-4, CD86 and PDCD1 gene polymorphisms and the incidence of allograft rejection susceptibility. Eligible articles were included for data extraction. The main outcome was the frequency of co-stimulate molecule gene polymorphisms between rejection and non-rejection populations. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Significant associations of the CD28 IVS3 +17T/C variant with acute allograft rejection susceptibility were found (CC +CT/TT OR, 1.45; 95% CI, 1.08-1.94; P=0.01). Also we found an association of the CD28 IVS3 +17T/C variant with kidney allograft rejection cases (CC +CT/TT OR, 1.72; 95% CI, 1.19-2.49; P=0.004) and (C allele OR, 1.74; 95% CI, 1.11-2.75; P=0.02), but not established for liver allograft rejection cases (CC +CT/TT OR, 1.19; 95% CI, 0.47-2.98; P=0.72) and (C allele OR, 0.96; 95% CI, 0.67-1.39; P=0.84). And we found an association of the CD86 +1057G/A variant with non-allograft rejection cases (AA +AG/GG OR, 0.35; 95% CI, 0.14-0.85; P=0.02). This meta-analysis demonstrates that the CD28 IVS3 +17T/C variant might increase acute allograft rejection risk in kidney transplant but not in liver transplant, and there was an association between CD86 +1057G/A variant and reduced acute rejection risk. Further studies will be needed to confirm our findings.

SIMULTANEOUS DETERMINATION OF HYDRAZINE, METHYLHYDRAZINE, AND 1,1-DIMETHYLHYDRAZINE IN RAT PLASMA BY LC–MS/MS

□ A rapid and sensitive analytical method of liquid chromatography combined with tandem mass spectrometry (LC–MS/MS) was established for simultaneous quantitative analysis of hydrazine, methylhydrazine, and 1,1-dimethylhydrazine in rat plasma. Plasma samples were pretreated with protein precipitation and optimized derivatization procedure. Separation was achieved using acetonitrile and water containing 5 mM ammonium acetate as gradient elution. The optimized mass transition ion-pairs (m/z) monitored for three hydrazine derivatives were m/z 299.1→m/z 151.1, m/z 180.2→m/z 78.1, and m/z 194.2→m/z 59.1, respectively. The lower limit of quantitation (LLOQ) of hydrazine was 1 ng/mL and those of other compounds were 10 ng/mL. Intra- and inter-day precision were within 14.00%. Meanwhile, the relative error was within the acceptable range. The recovery of three analytes and (IS) were between 57.78 ± 4.73%and 107.04 ± 7.46%. Target derivatives were stable under the conditions tested. The dilution test showed that this method is not only suitable for samples in the detection limit but also applicable for high concentration samples that exceed the upper limit of detection. The performance of the method was successfully verified for real rat plasmas and would be useful for routine analysis in cases of suspected hydrazine poisoning.

Protective effect of curcumin against cytomegalovirus infection in Balb/c mice

Curcumin has been found to suppress the activity of human cytomegalovirus (HCMV) in vitro, whereas its protective effects against HCMV infection in vivo remain unclear. In this study, we aimed to investigate the protective effects of curcumin against HCMV infection in Balb/c mice. Mice were randomly divided into the control, model, model+ganciclovir (positive control), and model+high-dose, model+middle-dose, and model+low-dose curcumin groups. In the model groups, each mouse was given HCMV by tail injection intravenously. Positive control animals were given ganciclovir. Animals in the curcumin treatment groups were given different concentrations of curcumin. The anti-HCMV activities of ganciclovir and curcumin were assessed by serological examination and pathology. Ganciclovir and curcumin treatment reduced the HCMV IgM level and HCMV DNA load; decreased the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) generation in infected mice. These treatments also suppressed malondialdehyde (MDA) content and upregulated superoxide dismutase (SOD) and glutathione (GSH) levels. In addition, both treatments prevented pathological changes of the lung, kidney, liver, and heart tissues in infected mice. Our findings indicate that curcumin protected Balb/c mice against HCMV infection possibly by its anti-inflammatory and antioxidant effects.

Effects of the NQO1 609C>T Polymorphism on Leukemia Susceptibility: Evidence from a Meta-analysis

A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta- analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR = 1.23, 95%CI = 1.00 - 1.51, heterogeneity = 0.76; I2 = 0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed.

Curcumin inhibits human cytomegalovirus by downregulating heat shock protein 90

Curcumin is a traditional Chinese medicine extracted from the rhizome of the herb Curcuma longa, which exhibits anti-human cytomegalovirus (HCMV) activity, however, the underlying mechanism remains to be elucidated. The present study reported that the pharmacogenomics of curcumin are similar to that of the antiviral drug, geldanamycin, which targets heat shock protein 90 (Hsp90). Comparative analysis of 3,000 clinical drugs demonstrated that curcumin had a positive association with the gene expression profiles of several drugs, among which the pharmacogenomics of the antiviral drug, geldanamycin, were most similar to that of curcumin. Molecular docking simulation analysis revealed that curcumin fit well in the binding pocket of Hsp90, with hydrogen bonds, hydrophobic interactions and conjugation to maintain adhesion. Consistently, HCMV infection of human embryonic lung fibroblast cells resulted in increased expression of Hsp90α, which was significantly inhibited by treatment with curcumin. These findings suggested that targeting Hsp90 contributed to the anti‑HCMV activity of curcumin.

Mechanism of curcumin resistance to human cytomegalovirus in HELF cells.

BackgroundWe have previously shown that curcumin exhibited an outstanding anti-HCMV effect in vitro and in vivo. However, the underlying mechanism for the anti-HCMV effect remains unclear.MethodsLevels of IL-6 and TNF-α cytokine secretions in HELF cells were determined by enzyme-linked immunosorbent assay (ELISA); cell cycles were assessed by flow cytometry; ie and ul83 gene expressions were evaluated using reverse transcriptase real-time quantitative PCR; HCMV IE and UL83 antigen expressions were studied using immunofluorescence staining assay and western blot.ResultsCurcumin reduced HCMV immediate early antigen (IEA) and UL83A expressions and IL-6, and TNF-α secretions and recovered cell proliferation to normal level in HCMV infected HELF cells.ConclusionsCurcumin anti-HCMV effect may possibly be that curcumin concurrently alters host cell microenviroment and inhibits the HCMV antigen expressions. These findings may provide a basic understanding of the curcumin anti-HCMV effect and a novel strategy for further development of curcumin anti-HCMV treatment.

Human cytomegalovirus infection and vascular disease risk: A meta-analysis.

BACKGROUND Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease. Numbers studies were conducted to analyze the association between HCMV infection and risk of vascular disease, but no clear consensus had been reached. The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. METHODS We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: (1) evaluating the association between HCMV infection and vascular disease; (2) case-control studies or nested case-control studies; (3) and supply the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. Ultimately, We included data from 68 studies, which altogether enrolled 12027 cases and 15386 controls from 24 countries. RESULTS HCMV IgG was detected 7376 in 10611 cases, HCMV IgM was detected 153 in 1486 cases and HCMV DNA was detected 654 in 2139 cases. Overall, people exposed to HCMV infection had higher risk than those not exposed for vascular disease (OR 1.70 [95% CI 1.43-2.03] IgG-based HCMV tests, 2.88 [95% CI 1.87-4.43] IgM-based HCMV tests and 2.56 [95% CI 1.46-4.49 PCR-based HCMV tests]). HCMV infection was clearly identified as a risk factor for vascular disease in Asian group, Caucasian group and other group, especially Asian group(OR 1.86 [95% CI 1.33-2.60] IgG-based HCMV tests, 3.57 [95% CI 1.94-6.60] IgM-based HCMV tests and 4.09 [95% CI 3.10-5.40 PCR-based HCMV tests]). CONCLUSION This meta-analysis suggested that HCMV infection is associated with an increased risk for vascular disease.

Cytomegalovirus infection and atherosclerosis risk: A meta‐analysis

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta‐analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta‐analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non‐atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG‐based HCMV tests, IgM‐based tests, PCR‐based tests, and pp65‐based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09‐4.51), 8.92(95%CI 3.17‐25.11), 6.75 (95%CI 3.50‐13.02), and 5.72(95%CI 1.51‐21.58), respectively. The meta‐analysis results showed that HCMV infection is significant connected with an increased risk for AS.