The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp′-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp′-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp′-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp′-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.

Heart failure (HF) is a disease with high morbidity and mortality. In patients with HF, decreased cardiac output and blood redistribution results in decreased intestinal perfusion and destruction of intestinal barrier. Microorganisms and endotoxins can migrate into the blood circulation, aggravating systemic inflammation and HF. Trimethylamine N-oxide (TMAO) is highly closed to the occurrence of HF. However, the exact mechanism between TMAO and HF remains unclear. To investigate the role of TMAO in transverse-tubule (T-tubule) in the cultured cardiomyocytes. T-tubule imaging and analysis detected T-tubule network in cardiomyocytes. Ca 2+ handling dysfunction was identified by confocal Ca 2+ imaging. Tubulin densification and polymerization were assessed by western blot and immunofluorescent staining of cardiomyocytes. TMAO induced T-tubule network damage in cardiomyocytes and Ca 2+ handling dysfunction in cardiomyocytes under the TMAO stress via promoting tubulin densification and polymerization and therefore Junctophilin-2 (JPH2) redistribution. Mice treated with TMAO represented cardiac dysfunction and T-tubule network disorganization. TMAO impairs cardiac function via the promotion of tubulin polymerization, subsequent translocation of JPH2, and T-tubule remodeling, which provides a novel mechanism for the relationship between HF and elevated TMAO.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Tripterine is an important active component isolated from Triperygium wilfordii Hook F. This study investigated the effects of tripterine on breast cancer cell proliferation, migration, invasion and apoptosis, as well as microRNA-15a (miR-15a) expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure the expression of miR-15a. Cell transfection was conducted to change the expression of miR-15a. Viability, proliferation, migration, invasion and apoptosis of MDA-MB-231 cells were assessed using the cell counting kit-8 (CCK-8) assay, BrdU incorporation assay, Annexin V-FITC/PI apoptosis detection kit and two-chamber Transwell assay, respectively. Expression of key factors involving in cell proliferation, migration, invasion and apoptosis, as well as the PI3K/AKT and JNK pathways, were evaluated using Western blotting. We found that tripterine inhibited MDA-MB-231 cell viability, proliferation, migration and invasion, but induced cell apoptosis. Moreover, tripterine up-regulated the expression of miR-15a in a concentration-dependent manner and miR-15a participated in the effects of tripterine on MDA-MB-231 cell proliferation, migration, invasion and apoptosis. In addition, tripterine inactivated PI3K/AKT and JNK pathways in MDA-MB-231 cells by up-regulating miR-15a. In conclusion, tripterine inhibited proliferation, migration and invasion of breast cancer MDA-MB-231 cells by up-regulating miR-15a and inactivating PI3K/AKT and JNK pathways.

Background: There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine. Methods: From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database. Results: The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species. Conclusions: Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.

Oral squamous cell carcinoma (OSCC) is one of the most fatal types of oral cancer worldwide. Forkhead box M1 (FOXM1) is associated with the occurrence and development of a number of types of human cancer, but its function in OSCC remains unclear. The present study aimed to explore the effect of FOXM1 downregulation using lentivirus-mediated short hairpin (sh)RNA against FOXM1 (LV-shFOXM1) in the cell line Tca8113 in vitro. Infection of Tca8113 cells with LV-shFOXM1 inhibited the mRNA and protein expression level of FOXM1. The downregulation of FOXM1 resulted in cell cycle arrest of Tca8113 cells, and the inhibition of proliferation, migration and invasion. The protein expression level of cyclins B1 and D1 were downregulated, whereas those of p27 and p21 were upregulated following infection with LV-shFOXM1, compared with the blank control and LV-shCON groups. In addition, FOXM1 downregulation decreased the expression of matrix metalloproteinase-2 and LV-shFOXM1 significantly suppressed OSCC cell viability. Therefore, FOXM1 may be a target for the treatment of OSCC. Materials and methods Cell culture reagents. Human HaCaT, Tca8113 and SCC9 cells were purchased from the American Type Culture Collection (Manassas, VA, USA). SCC9 cells were kept in a 1:1 mixture of Dulbecco's modified Eagle's medium (DMEM) and Ham's F12 medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin/streptomycin solution (all from