CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.     

N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway

Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl₄)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl₄-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl₄-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl₄-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.     

MTHFR polymorphisms and breast cancer risk

Introduction

Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumour cells.

Material and methods

We evaluated these two common polymorphisms and breast cancer risk association in an Iranian sporadic breast cancer population-based case-control study of 294 breast cancer cases and 306 controls using a PCR-RFLP-based assay.

Results

Analyses of affected and controls show that homozygote genotype MTHFR 677CC has the highest frequency in both groups (28.3% in patients and 25.3% in control group). Genotype MTHFR 677CT and genotype MTHFR 1298AC were found to be statistically significant risk factors in our population (odds ratio: 1.6, 95% CI: 1.019-2.513, p = 0.041; and odds ratio: 2.575, 95% CI: 1.590-4.158, p = 0.001 respectively).

Conclusions

We can conclude based on the results of our study that a significant association between breast cancer and C677T and A1298C polymorphism might exist.     

Klotho gene polymorphisms are related to colorectal cancer susceptibility

Aim: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. Methods: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. Results: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437-12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). Conclusion: G-395A polymorphism of Klotho gene could increase the risk of CRC.     

MicroRNA301 is a potential diagnostic biomarker for hepatocellular cancer

We explored microRNA301 diagnosis value in hepatocellular cancer (HCC), attempting to provide novel insights for early detection, effective prevention, and timely treatment. 42 patients with HCC and 38 controls composed of 9 liver cirrhosis (LC), 9 chronic hepatitis B (CHB) and 20 healthy individuals were investigated in the study. Serum microRNA301 expression levels were detected using fluorescent quantitative polymerase chain reaction (FQ-PCR) technology. ROC curve was performed to evaluate diagnosis value of microRNA301. Meanwhile, the correlations of microRNA301 levels with clinical characteristics were also analyzed. Significantly up-regulated expression of serum microRNA301 was seen in HCC patients compared with the controls (P < 0.05). We also noted that level changes of microRNA301 were associated with differentiation, alpha fetoprotein (AFP), portal vein-emboli and HasAg (P < 0.05), rather than age, gender and tumor size. Based on the area under ROC curve of 0.880, the critical value of microRNA301 was 2.3530 and the sensitivity and specificity were 88.1% and 70.3%, respectively. The results of this study revealed that microRNA301 might function as a potential diagnostic biomarker for HCC.     

CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.     

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.     

RET polymorphisms might be the risk factors for thyroid cancer

Aims: The purpose of the study is to investigate the relationship between rs1799939, rs1800858 and rs74799832 polymorphisms of RET with thyroid cancer (TC) susceptibility. Methods: Genotypes distribution of control groups were tested by Hardy-Weinberg equilibrium (HWE). Rs1799939, rs1800858 and rs74799832 polymorphisms of RET were researched in 135 patients with TC and 135 healthy people using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the association between RET polymorphisms and the risk of TC by Chi-squared test. Results: Genotypes frequencies of the control group were consistent with HWE. The frequency of genotype AA and allele A in rs1799939 were significantly higher in patients with TC than controls (OR=3.768, P=0.046; OR=1.695, P=0.035). Genotype GG and allele G of rs1800858 remarkably increased the risk of TC (OR=2.149, P=0.039; OR=1.45, P=0.039). Moreover, CC genotype and C allele in rs74799832 polymorphism was related with TC susceptibility. (OR=2.28, P=0.049; OR=1.566, P=0.049). Conclusion: In present result, RET rs1799939, rs1800858 and rs74799832 polymorphisms might be the risk factors for TC.     

HOXD13 methylation status is a prognostic indicator in breast cancer

Homeobox protein Hox-D13 is encoded by HOXD13 gene which is frequently methylated in cancer and has been recognized as a tumor suppressor in pancreatic cancer. In this study, we examined HOXD13 mRNA expression in 40 pairs of breast cancers and corresponding normal breast tissues. Bisulfite sequencing of HOXD13 promoter was performed in 6 pairs of breast tumors and corresponding normal breast tissues to examine the potential HOXD13 CpG methylated sites. HOXD13 DNA methylation frequency analysis was performed using MethyLight in 196 pairs of breast cancers and corresponding normal breast samples. DNA methylation status and clinico-pathological features were investigated. Kaplan-Meier survival analysis and Cox proportional hazards models were utilized to assess the effect of methylation status on overall survival. We found that 60% (24/40) of breast cancers showed low HOXD13 mRNA expression when compared with corresponding normal breast tissue. The predicted CpG island was located in the -1325 bp to +675 bp region. Next, the -332 bp site in HOXD13 gene promoter was further examined and in 57.7% (113/196) samples methylation was detected at this site. HOXD13 methylation was correlated with larger tumor size (P = 0.004), but not with other clinico-pathological parameters. In addition, patients with methylated -HOXD13 promoter had worse overall survival (OS) (P = 0.005). Based on our results we conclude that HOXD13 methylation is a common event in primary breast cancer and is associated with poor survival of breast cancer patients. HOXD13 methylation could therefore potentially be used as a prognostic factor for breast cancer.     

Single-nucleotide polymorphism analysis of GH, GHR,and IGF-1 genes in minipigs

Tibetan (TB) and Bama (BM) miniature pigs are two popular pig breeds that are used as experimental animals in China due to their small body size. Here, we analyzed single-nucleotide polymorphisms (SNPs) in gene fragments that are closely related to growth traits [growth hormone (GH), growth hormone receptor (GHR), and insulin-like growth factor (IGF)-1)] in these pig breeds and a large white (LW) control pig breed. On the basis of the analysis of 100 BMs, 108 TBs, and 50 LWs, the polymorphic distribution levels of GH, GHR, and IGF-1 were significantly different among these three pig breeds. According to correlation analyses between SNPs and five growth traits - body weight (BW), body length (BL), withers height (WH), chest circumference (CC), and abdomen circumference (AC) - three SNP loci in BMs and four SNP loci in TBs significantly affected growth traits. Three SNP sites in BMs and four SNP sites in TBs significantly affected growth traits. SNPs located in the GH gene fragment significantly affected BL and CC at locus 12 and BL at locus 45 in BMs, and also BW, WH, CC, and AC at locus 45 and WH and CC at locus 93 in TBs. One SNP at locus 85 in the BM GHR gene fragment significantly affected all growth traits. All indices were significantly reduced with a mixture of alleles at locus 85. These results provide more information regarding the genetic background of these minipig species and indicate useful selection markers for pig breeding programs.     

Qiliqiangxin improves cardiac function and attenuates cardiac remodeling in rats with experimental myocardial infarction

Objective: It has been reported that Qiliqiangxin (QL), a traditional Chinese medicine compound, could inhibit cardiac hypertrophy and remodeling, and improve cardiac function. However, whether and how it reverses cardiac remodeling in rats post myocardial infarction (MI) remains unknown. This study aims to explore related mechanisms linked with cardiac function improvement and attenuation of cardiac remodeling by QL in rats with experimental MI. Methods: MI was induced by ligation of left anterior descending coronary artery (LAD) in male Sprague-Dawley rats. Rats with LVEF < 50% at four weeks after procedure were treated for another 6 weeks with placebo, QL and captopril. Echocardiography and plasma NT-proBNP were measured at the end of study, and histological studies were performed. Protein expressions of Neuregulin-1 (NRG-1), total-Akt, phospho-Akt (Ser473), hydroxy-HIF-1α (Pro564), VEGF, Bax, Bcl-2 and Caspase 3 were examined by Western blot. mRNA expression of NRG-1 and p53 was detected by real-time PCR. Results: Compared with the placebo group, QL improved cardiac function, reduced left ventricular dimension, inhibited interstitial inflammation and fibrosis, increased neovascularization, and attenuated cardiomyocyte apoptosis. Meanwhile QL significantly upregulated the expression of HIF-1α, VEGF, enhanced phosphorylation of Akt, decreased the ratio of Bax/Bcl-2 and Caspase 3 expression. Furthermore, we observed upregulation of NRG-1 and downregulation of p53 after QL treatment. Conclusion: Our data suggest that the beneficial effects of QL on improving cardiac function and attenuating cardiac remodeling post MI are associated with angiogenesis enhancement and apoptosis inhibition, which may be mediated via activation of NRG-1/Akt signaling and suppression of p53 pathway.     

Intracystic papillary breast carcinoma with areas of infiltration : Report on two cases

Intracystic papillary carcinoma of the breast associated with areas of infiltration is rare in that it constitutes less than 1% of breast cancers. After initial radiological study, these tumors show lesions with little likelihood of malignancy in a high proportion of cases.Two cases of intracystic papillary carcinoma associated with infiltration were diagnosed at the Breast Unit of Hospital Infanta Cristina. In both cases, the reason for consultation arose after palpation of a nodule and the initial radiographic analyses showed lesions with little likelihood of malignancy.     

CTLA-4 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease

Objective: The aim of this study was to investigate whether four single nucleotide polymorphisms (SNPs) in CTLA-4 gene are associated with chronic obstructive pulmonary disease (COPD) in a Chinese population. Methods: Samples were collected from a Chinese population and analyzed for the association of SNPs in CTLA-4 gene with COPD in a case-control study. Four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were chosen and genotyped. The results were then analyzed using statistical methods. Results: We found that none of these four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were associated with the disease. Conclusion: Our data suggested that there was no significant association between these four SNPs in CTLA-4 gene and COPD susceptibility in a Chinese population.     

Candida species and other yeasts in the oral cavities of type 2 diabetic patients in Cali,Colombia

Objective:

To determine the prevalence of Candida species and to study factors associated to oral cavity colonization in patients with type 2 diabetes mellitus.

Methods:

A total of 107 diabetics were classified into controlled and uncontrolled according to glycosylated hemoglobin values. Each patient was assessed for stimulated salivary flow rates, pH, and an oral rinse to search for yeast. The study also determined the state of oral health via Klein and Palmer CPO indexes for permanent dentition, dental plaque by O''Leary, and a periodontal chart.

Results:

We found yeasts in 74.8% of the patients. A total of 36 of the 52 subjects with controlled diabetes presented yeasts and 44 in the uncontrolled; no significant differences (p = 0.2) were noted among the presence of yeasts and the control of blood glucose. The largest number of isolates corresponded to C. albicans, followed by C. parapsilosis. Uncontrolled individuals presented a significantly higher percentage of yeast different from C. albicans (p = 0.049).

Conclusions:

We found a high percentage of Candida colonization and uncontrolled individuals had greater diversity of species. The wide range of CFU/mL found both in patients with oral candidiasis, as well as in those without it did not permit distinguishing between colonization and disease. We only found association between isolation of yeasts and the low rate of salivary flow.     

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptorCTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.     

Cocos nucifera (L.) (Arecaceae): A phytochemical and pharmacological review

Cocos nucifera (L.) (Arecaceae) is commonly called the “coconuttree” and is the most naturally widespread fruit plant on Earth. Throughout history,humans have used medicinal plants therapeutically, and minerals, plants, and animalshave traditionally been the main sources of drugs. The constituents of C.nucifera have some biological effects, such as antihelminthic,anti-inflammatory, antinociceptive, antioxidant, antifungal, antimicrobial, andantitumor activities. Our objective in the present study was to review thephytochemical profile, pharmacological activities, and toxicology of C.nucifera to guide future preclinical and clinical studies using thisplant. This systematic review consisted of searches performed using scientificdatabases such as Scopus, Science Direct, PubMed, SciVerse, and Scientific ElectronicLibrary Online. Some uses of the plant were partially confirmed by previous studiesdemonstrating analgesic, antiarthritic, antibacterial, antipyretic, antihelminthic,antidiarrheal, and hypoglycemic activities. In addition, other properties such asantihypertensive, anti-inflammatory, antimicrobial, antioxidant, cardioprotective,antiseizure, cytotoxicity, hepatoprotective, vasodilation, nephroprotective, andanti-osteoporosis effects were also reported. Because each part of C.nucifera has different constituents, the pharmacological effects of theplant vary according to the part of the plant evaluated.     

Antibacterial activity and mechanism of berberine against Streptococcus agalactiae

The antibacterial activity and mechanism of berberine against Streptococcus agalactiae were investigated in this study by analyzing the growth, morphology and protein of the S. agalactiae cells treated with berberine. The antibacterial susceptibility test result indicated minimum inhibition concentration (MIC) of berberine against Streptococcus agalactiae was 78 μg/mL and the time-kill curves showed the correlation of concentration-time. After the bacteria was exposed to 78 μg/mL berberine, the fragmentary cell membrane and cells unequal division were observed by the transmission electron microscopy (TEM), indicating the bacterial cells were severely damaged. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) study demonstrated that berberine could damage bacterial cells through destroying cellular proteins. Meanwhile, Fluorescence microscope revealed that berberine could affect the synthesis of DNA. In conclusion, these results strongly suggested that berberine may damage the structure of bacterial cell membrane and inhibit synthesis of protein and DNA, which cause Streptococcus agalactiae bacteria to die eventually.     

MOK overexpression is associated with promoter hypomethylation in patients with acute myeloid leukemia

Overexpression of MAPK/MAK/MRK overlapping kinase (MOK) has been found in various tumors. However, the mechanism underlying MOK upregulation remains unclear. A CpG island was identified in MOK promoter. In this study, we evaluated the expression and methylation status of MOK gene in acute myeloid leukemia (AML). Hypomethylation of MOK promoter was detected in 31.0% (45/145) of AML patients. The degree of MOK hypomethylation was significantly correlated with MOK expression in AML patients. MOK-hypomethylated patients had a trend towards lower WBCs. Receiver operating characteristic curve (ROC) analysis showed a good performance in distinguishing AML patients from controls with an area under the ROC curve (AUC) of 0.820 (P < 0.001). In summary, our results suggest MOK promoter hypomethylation is a common event and contributes to MOK overexpression in AML.