Search

Background Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a major public health problem and its pathogenesis remains unresolved. A recent proteomics study discovered a lipid enzyme Sterol O-acyltransferase (SOAT1) involvement in the progression of HCC. We aimed to explore the association between SOAT1 genetic variation and HCC. Methods We genotyped three exonic SOAT1 variants (rs10753191, V323V; rs3753526, L475L; rs13306731, Q526R) tagging most variations in the gene, in 221 HCC patients and 229 healthy individuals, to assess the impact of SOAT1 gene variation on risk of HCC occurrence. We further conducted immunohistochemistry to compare SOAT1 protein expression levels in 42 paired tumor and adjacent non-tumor tissues. Results We found that rs10753191 (Odds ratio (OR) = 0.58, P = 0.04) and a haplotype TGA (OR = 0.40, P = 0.01) were associated with reduced HCC risk after adjusting for lipid levels. In the immunohistochemistry experiment, we found that the protein expression of SOAT1 was significantly increased in the tumor compared with adjacent tissue (P Conclusion This study revealed for the first time SOAT1 genetic variation that associates with host susceptibility to HCC occurrence. Our results suggest a role of SOAT1 in the HCC development, which warrants further elucidation.

Background Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency disease and frequently reported in the Western countries. However, large‐scale epidemiologic studies on SIgAD in China are still lacking. Methods The clinical information of 555 180 subjects (age >4 years) including the outpatient, inpatient, and healthy subjects who had ordered serum immunoglobulin A, G, M in 9 hospitals of Zhejiang Province in China was collected. The SIgAD individuals were defined as IgA level age >4 years). For adults, the common clinical features were infections (43/87, 49.43%), autoimmune disorders (31/87, 35.63%), allergic cases (5/87, 5.75%), and tumor cases (4/87, 4.60%). Additionally, infectious diseases (20/22, 90.91%), autoimmune disorders (4/22, 18.18%), and allergic cases (1/22, 4.55%) were found in 22 children. Conclusion We first describe a large cohort of SIgAD individuals of Zhejiang Province in China. The incidence was 0.020%. The common clinical features were infection, autoimmune disorders, tumor, and allergy, and the infection rate was higher in children than the adults.

// Xunjun Yang 1, 2 , Xiuchan Guo 1, 3 , Yao Chen 4 , Guorong Chen 4 , Yin Ma 1 , Kate Huang 4 , Yuning Zhang 1 , Qiongya Zhao 1 , Cheryl A. Winkler 5 , Ping An 5 , Jianxin Lyu 1 1 Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China 2 Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 3 ICF International, Atlanta, GA, USA 4 Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 5 Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA Correspondence to: Ping An, email: anp@mail.nih.gov Jianxin Lyu, email: ljx@wmu.edu.cn Keywords: hepatocellular carcinoma, TERT, mutation, telomerase reverse transcriptase Received: February 01, 2016 Accepted: March 28, 2016 Published: April 1, 2016 ABSTRACT Telomerase reverse transcriptase ( TERT ) promoter mutations are among the most frequent noncoding somatic mutations in multiple cancers, including hepatocellular carcinoma (HCC). The clinical and pathological implications of TERT promoter mutations in hepatitis B virus (HBV)-associated HCC have not been resolved. To investigate TERT promoter mutations, protein expression, and their clinical-pathological implications, we sequenced the TERT promoter region for hotspot mutations in HCC tissues and performed immunostaining for TERT protein expression from HBV-associated HCC in Chinese patients. Of 276 HCC tumor DNA samples sequenced, 85 (31%) carried TERT promoter mutations. TERT promoter mutations were more frequent in those with low α-fetoprotein (AFP) serum levels ( p = 0.03), advanced age ( p = 0.04), and in those lacking HCC family history ( p = 0.02), but were not correlated with HCC stages and grades. TERT protein levels were higher in HCC (n = 28) compared to normal liver tissues (n = 8) ( p =0.001), but did not differ between mutated and non-mutated tumor tissues. In conclusion, TERT promoter mutations are common somatic mutations in HCC of Han Chinese with HBV infection. Detection of TERT promoter mutations in those with low levels of AFP may aid diagnosis of HCC with atypical presentation.

Increased rates of exposure to Toxoplasma gondii have been found in patients with psychiatric disorders globally, but there is scarce information about the epidemiology of T. gondii infection in psychiatric patients in Zhejiang Province, Southeastern China. In a case-control survey, we measured IgG and IgM class antibodies against T. gondii in 798 patients from a public psychiatric hospital in the city of Wenzhou, Zhejiang Province, and in 681 non-psychiatric controls from the general population in the same region. Subjects in each group were matched by sex and age with an enzyme-linked immunoassay. Seroprevalence of anti-Toxoplasma IgG antibodies in psychiatric patients (13.3%, 106/798) was significantly higher than in the control population (9.4%, 64/681) (P = 0.022). Anti-Toxoplasma IgM antibodies were also significantly higher in the psychiatric patients (4.1%, 33/798) than in the control group (1.9%, 13/681) (P = 0.016). Additionally, we found significantly elevated seropositive rates of anti-Toxoplasma IgG and IgM in patients with schizophrenia, as well as those with bipolar disorder. The identification of specific anti-Toxoplasma antibodies in psychiatric patients may be useful for assessing infection and timely initiation of treatment.

To explore the role of mitochondrial DNA 5178 C/A (Mt5178) polymorphism of NADH-dehydrogenase subunit 2 (ND2) gene in type-2 diabetes mellitus (T2DM) among ethnic Han Chinese through a case-control study.The Mt5178C/A polymorphism was determined by sequencing 1103 T2DM patients and 791 healthy controls. Logistic regression analysis was conducted to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm the results, a meta-analysis was conducted based on published literature on the association of Mt5178 variant with T2DM.No significant association was found between the Mt5178C/A variant and T2DM either by our study or the meta-analysis which included eight published studies. Nevertheless, it was found that the T2DM patients with 5178C genotype were at a higher risk for nephropathy complication (OR=1.49, 95%CI: 1.005-2.197, P0.05) and at significantly lower risk for hypertension complication (OR=0.744, 95%CI: 0.556-0.996, P0.05) compared with those carrying a 5178A genotype.No association was found between the Mt5178C/A polymorphism of mitochondrial ND2 gene with the increased risk of T2DM. However, the polymorphism may affect the development of nephropathy and hypertension complications among T2DM patients.

Emerging evidence indicates that methylglyoxal (MG) can inhibit tumorigenesis. Glyoxalase I (GLOI), a MG degradation enzyme, is implicated in the progression of human malignancies. However, little is known about the roles of MG and GLOI in breast cancer. Our purpose was to investigate the anticancer effects of MG and inhibition of GLOI on breast cancer cells and the underlying mechanisms of these effects. Our findings demonstrate that cell viability, migration, invasion, colony formation, and tubule formation were significantly restrained by addition of MG or inhibition of GLOI, while apoptosis was significantly increased. Furthermore, the expression of p-JNK, p-ERK, and p-p38 was markedly upregulated by addition of MG or inhibition of GLOI, whereas MMP-9 and Bcl-2 expression levels were dramatically decreased. These effects were augmented by combined treatment with MG and inhibition of GLOI. Collectively, these data indicate that MG or inhibition of GLOI induces anticancer effects in breast cancer cells and that these effects are potentiated by combination of the 2. These effects were modulated by activation of the MAPK family and downregulation of Bcl-2 and MMP-9. These findings may provide a new approach for the treatment of breast cancer.