Association between mixed exposure to endocrine-disrupting chemicals and cognitive function in elderly Americans.

OBJECTIVES: Studies exploring the relationship between mixed exposure to endocrine-disrupting chemicals (EDCs) and cognition are limited, with even more scarce studies conducted in the elderly. The aim of this study was to investigate the association between mixed exposure to five categories of EDCs and cognition in elderly Americans. STUDY DESIGN: Cross-sectional study. METHODS: 727 participants from the 2011-2014 National Health and Nutrition Examination Survey were incorporated into this study, and the levels of 47 EDC metabolites were measured. Cognitive function was assessed using immediate recall test (IRT), delayed recall test (DRT), animal fluency test (AFT), and digit symbol substitution test (DSST), and all the cognitive test scores were standardized. The individual and combined effects of EDC metabolites on the cognitive function in older adults were assessed using three analytical methods. RESULTS: The results showed that exposure to perfluorononanoic acid, polychlorinated biphenyl (PCB) 199, and PCB 206 was associated with the z-scores on the cognitive tests. Negative associations between mixed exposure to EDCs and the AFT and Global z-scores and a positive relationship with the DRT z-score were found in the WQS regression. The BKMR results revealed a positive trend between the mixture of EDCs and the DRT z-score. However, compared to the median, exposure to mixtures in the 45th percentile and below was associated with a decreased DRT z-score. CONCLUSIONS: Mixed exposure to EDCs may adversely affect the global cognitive function in elderly individuals. Necessary measures are needed to restrict EDCs use to protect the cognitive health of older adults.

Correlations of mouse lymphoma xenografts with the expressions of MMP-9 and Bcl-2.

The article "Correlations of mouse lymphoma xenografts with the expressions of MMP-9 and Bcl-2, by C.-L. Shi, X.-Y. Zhang, Y. Li, L.-L. Song, L. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (3): 1176-1183-DOI: 10.26355/eurrev_201902_17010-PMID: 30779087" has been retracted by the authors as they believe that they have not yet fully studied their work and have discovered some great new results. Therefore, they will rearrange the manuscript and try to provide a more accurate model. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17010.

Correlation between AT1R gene polymorphism and epilepsy secondary to cerebral infarction.

OBJECTIVE: To explore the correlation between angiotensin II type 1 receptor (AT1R) gene polymorphism and epilepsy secondary to cerebral infarction and its significance for the diagnosis of this disease. PATIENTS AND METHODS: A total of 200 patients with epilepsy secondary to cerebral infarction were enrolled from our hospital as observation group, and 200 patients without epilepsy after cerebral infarction as control group. Genomic deoxyribonucleic acids (DNAs) were extracted from the peripheral blood of the subjects, and the polymorphic regions at AT1R gene loci rs380400, rs1799870, rs12721273, and rs55707609 were amplified via polymerase chain reaction (PCR) and sent to the company for sequencing. The concentration of farnesyl diphosphate synthase (FDPS) was determined using enzyme-linked immunosorbent assay (ELISA) kit, and activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured in the Laboratory Department. RESULTS: There were no differences in the allele distributions at AT1R gene loci rs380400 (p=0.070), rs179987 (p=0.0.280), and rs55707609 (p=0.046), but in the allele distribution at rs12721273 (p=0.001) between control group and observation group, and observation group exhibited a significantly lower frequency of allele G in cerebral infarction patients than control group [153 (0.383) vs. 198 (0.495)]. The frequency of genotype GT at rs12721273 was lower [71 (0.355)] and that of genotype TT was evidently higher [88 (0.440)] in observation group (p=0.000). Control group showed a notably lower frequency of genotype AA [47 (0.235)] and a markedly higher frequency of genotype AT [110 (0.550)] at rs55707609 (p=0.000). Observation group exhibited a substantially lower frequency of recessive model AG+GG [128 (0.640)] (p=0.037), and a notably higher frequency of homozygous model AA [72 (0.360)] (p=0.048) at AT1R gene locus rs380400, a remarkably lower frequency of dominant model GG+GT [112 (0.560)] (p=0.002) at rs12721273, and a significantly lower frequency of recessive model AT+TT [126 (0.630)] (p=0.000) and a considerably lower frequency of heterozygous model AT [84 (0.420)] (p=0.026) at rs55707609. The frequencies of AT1R gene haplotypes ACGA (p=0.001), ACGT (p=0.045), ACTT (p=0.000), ATTT (p=0.048), GCTA (p=0.000), and GTGA (p=0.005) in observation group were distinctly higher than those in control group, and the frequencies of the haplotypes ACTA (p=0.000) and ATTA (p=0.029) were evidently lower than those in control group. The loci rs12721273 and rs1799870 showed a significant association (D'=0.783), and APTT was considerably correlated with genotype AG at rs380400 (p=0.042), PT with genotype CC at rs1799870 (p=0.002) and FDPS with genotype AA at rs55707609 (p=0.015). CONCLUSIONS: The polymorphisms of AT1R gene loci rs380400, rs1799870, rs12721273, and rs55707609 are correlated with the susceptibility to epilepsy secondary to cerebral infarction.

Long noncoding RNA ROR1­AS1 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/ß-catenin/EMT signaling cascade in cervical cancer.

OBJECTIVE: Several long noncoding RNAs (lncRNAs) display functional effects in the tumorigenesis and progression of cervical cancer (CC). We aimed to investigate the roles of lncRNA tyrosine protein kinase transmembrane receptor 1 antisense RNA 1 (ROR1­AS1) in the development of CC patients. PATIENTS AND METHODS: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed for the determination of ROR1­AS1 levels in both CC tissues and cell lines. The clinical value of ROR1­AS1 expression in CC patients was statistically analyzed. After transfection with si-ROR1­AS1 in SiHa and HeLa cells, cellular growth and apoptosis were examined by Cell Counting Kit (CCK-8) assay, cell colony formation, and flow cytometry. Then, wound-healing assays and transwell assays were performed to evaluate cell migration and invasion, respectively. The related proteins of epithelial-mesenchymal transition (EMT) markers and Wnt/ß-catenin signaling pathway was assessed using Western blot assays. RESULTS: We found that that the expressions of ROR1­AS1 were distinctly increased in CC tissues and cell lines. Clinical study revealed that high ROR1­AS1 expression was associated with distant metastasis, FIGO stage, and shorter five-year survival. Functional assays by performing in vitro assays revealed that inhibition of ROR1­AS1 distinctly suppressed CC cell proliferation, colony formation, migration and invasion, and promoted apoptosis. Based on results of Western blot, we showed that the downregulation of ROR1­AS1 inhibited the levels of N-cadherin and vimentin. In addition, the distinctly decreased levels of c-myc, ß-catenin, and cyclin D1 were observed in CC cells transfected with si-ROR1­AS1. CONCLUSIONS: Our results suggest that ROR1­AS1 is likely to serve as an efficient therapeutic approach in respect of CC treatment. Our results suggest that KLF5 may be a potential therapeutic target in laryngeal carcinoma.

Theacrine attenuates myocardial fibrosis after myocardial infarction via the SIRT3/ß-catenin/PPARγ pathway in estrogen-deficient mice.

OBJECTIVE: To investigate the role of theacrine in the protection of ventricular remodeling and chronic heart failure after myocardial infarction in the estrogen-deficient mice. MATERIALS AND METHODS: Female C57BL/6 mice aged 8 weeks old were selected and then subjected to bilateral oophorectomy. At 7 days after surgery, the models of the myocardial infarction were established by ligating the anterior descending coronary artery. On the first day after myocardial infarction, Theacrine (20 mg/kg) was administered via gavage for continuous 28 days. Thereafter, the cardiac function in each group of mice was detected via cardiac ultrasonography for small animals at 7, 14, and 28 days after surgery. The mice were sacrificed after 28 days. The infarct size of mice was determined through 2,3,5-triphenyltetrazolium chloride (TTC) and Evan blue double staining assay, while the myocardial fibrosis was assessed via Masson staining assay. The expression levels of collagen-related proteins Collagen I, Collagen III, alpha-smooth muscle actin (α-SMA), and the transforming growth factor-ß (TGF-ß) were measured by Western blotting (WB). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay was applied to evaluate the myocardial apoptosis, and the WB was employed to detect apoptosis-associated proteins. The expression level of silent information regulator 2 homologue 3 (SIRT3) protein was detected by immunohistochemistry, and the expression levels of SIRT3, ß-catenin and peroxisome proliferator-activated receptor gamma (PPARγ) protein were measured via WB. RESULTS: Compared with those in the Sham group, the ejection fraction (EF) and fractional shortening (FS) in estrogen-deficient mice were significantly lowered, the myocardial fibrosis and myocardial apoptosis were clearly aggravated, and the SIRT3 expression was decreased at 28 days after myocardial infarction. The theacrine could improve the cardiac function after the myocardial infarction in estrogen-deficient mice and relieve both myocardial fibrosis and myocardial apoptosis during chronic remodeling after myocardial infarction in estrogen-deficient mice. After the intervention with theacrine, the estrogen-deficient mice with myocardial infarction had up-regulated SIRT3 and PPARγ levels and a reduced ß-catenin level in the heart. CONCLUSIONS: Theacrine is able to activate SIRT3 and repress myocardial fibrosis and apoptosis after myocardial infarction in ovariectomized mice, thereby improving the cardiac function of ovariectomized mice with myocardial infarction through the possible downstream signal pathway ß-catenin/PPARγ.

Correlations of mouse lymphoma xenografts with the expressions of MMP-9 and Bcl-2.

OBJECTIVE: To establish a mouse lymphoma xenograft model so as to investigate the correlation between the expression of matrix metallopeptidase-9 (MMP-9) and that of B-cell lymphoma 2 (Bcl-2) in lymphomas. MATERIALS AND METHODS: Diffuse large Bcl (DLBCL) cells were cultured, and a mouse lymphoma xenograft model was established via the subcutaneous injection. Mouse lymphoma tissues were extracted, and the expressions of MMP-9 and Bcl-2 messenger ribonucleic acids (mRNAs) in the xenograft tumor were detected using Real-time polymerase chain reaction (PCR). Immunohistochemistry was used to detect the expression levels of MMP-9 and Bcl-2 proteins in lymphoma tissues and tumor-adjacent tissues. The consistency of MMP-9 expression and Bcl-2 expression was analyzed via Spearman's rank correlation analysis. RESULTS: The expressions of MMP-9 and Bcl-2 in lymphoma tissues were increased. The expression levels of MMP-9 and Bcl-2 proteins in lymphoma tissues were higher than those in tumor-adjacent tissues. The expression levels of MMP-9 and Bcl-2 were correlated with the body weight loss degree of mice, and the expression of MMP-9 was positively associated with that of BCL-2 in lymphomas. CONCLUSIONS: MMP-9 and Bcl-2 are associated with the onset of DLBCL, and they are potential impact factors affecting the prognosis.

LncRNA SNHG8 participates in the development of endometrial carcinoma through regulating c-MET expression by miR-152.

OBJECTIVE: To investigate the possible function and mechanism of lncRNA SNHG8 in the pathogenesis of endometrial carcinoma. PATIENTS AND METHODS: We utilized qRT-PCR to detect the expression of SNHG8 in 60 cases of endometrial carcinoma and 25 cases of normal endometrium; after that, the endometrial carcinoma cell lines were screened. SNHG8 was transfected into endometrial carcinoma cells by Lipofectamine and the proliferative activity of cells was detected by cell counting kit-8 (CCK-8) assay. Bioinformatics methods were used to detect the target microRNA. miR-152 is predicted to bind to SNHG8 and target genes of c-MET. Luciferase reporter assay was performed to detect the relative luciferase activity between miR-152 and c-MET, SNHG8. The interactions between SNHG8, miR-152, and c-MET were further verified by transfection of miR-152 mimics, miR-152 mimics + OE-SNHG8, SNHG8 siRNA, and SNHG8 siRNA + miR-152 inhibitor. RESULTS: SNHG8 expression in endometrial carcinoma tissue was significantly higher than that in normal endometrium. After transfection with SNHG8 siRNA, the cell viability of AN3CA cells decreased, whereas the activity of Ishikawa was increased after transfection with SNHG8 overexpression plasmid. Bioinformatics predictions and dual luciferase reporter assay illustrated that SNHG8 was bound to miR-152 and miR-152 targeted on c-MET. In addition, miR-152 mimics inhibited the expression of c-MET, and the inhibitory effect was reversed after SNHG8 overexpression. Silencing SNHG8 reduced c-MET expression, and c-MET expression was reversed after addition of miR-152 inhibitor. CONCLUSIONS: SNHG8 is highly expressed in endometrial carcinoma, and SNHG8 targets c-MET through miR-152 to regulate the proliferation of endometrial cancer cells.

IMPDH2 mediate radioresistance and chemoresistance in osteosarcoma cells.

OBJECTIVE: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Despite aggressive therapy, survival outcomes remain unsatisfactory, especially for patients with metastatic disease or patients with a poor chemotherapy response. Previous study founds inosine 5'-monophosphate dehydrogenase type II (IMPDH2) was an independent prognostic factor and observed frequent IMPDH2 overexpression in osteosarcoma patients with poor response to chemotherapy. In the present work, we provide evidence for direct involvement of IMPDH2 in the development of radioresistance and chemoresistance. MATERIALS AND METHODS: The expression of IMPDH2 was examined in OS cells. Stable cell lines overexpressing IMPDH2 and IMPDH2 knock-down cells were generated using the osteosarcoma cell line. The stable transfected cells, alone or in combination with cisplatin or γ-irradiation, was used to treat OS cells. The growth inhibitory and apoptotic effects of IMPDH2 in vitro and in vivo were examined. RESULTS: Overexpression of IMPDH2 in IMPDH2 poor-expressed U2OS cells induced strong cisplatin chemoresistance and γ-irradiation radioresistance through inhibition of apoptosis in vitro and in vivo. Knockdown of IMPDH2 in IMPDH2 rich-expressed Saos-2 cells resulted in significant chemosensitivity and γ-irradiation radiosensitivity through inducing of apoptosis in vitro and in vivo. CONCLUSIONS: IMPDH2 is directly involved in the development of chemoresistance and radioresistance in osteosarcoma cells, suggesting that targeting of IMPDH2 by shRNA in combination with chemotherapy and γ-irradiation might be a promising means of overcoming chemoresistance and radioresistance in osteosarcomas with high IMPDH2 expression.