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1.
Cell Signal ; 102: 110553, 2023 02.
Article in English | MEDLINE | ID: mdl-36473621

ABSTRACT

Bladder cancer (BCa) is a common malignancy with uncertain molecular mechanism. 7-dehydrocholesterol reductase (DHCR7), the enzyme of mammalian sterol biosynthesis, plays important roles in several types of cancers but its specific function in BCa is still unknown. The current study aimed to determine the bioinformatic characteristics and biological functions of DHCR7 in BCa. Sequencing results and clinical data from online public databases, human BCa tissues and matched noncancerous tissues, xenograft nude mice, DHCR7 deficiency and overexpression BCa cell (T24 and EJ) models were used. Several bioinformatics analyses were made, qRT-PCR, Western-blotting, flow cytometry, immunohistochemistry (IHC), MTT assay, wound healing and cell invasion assays were performed. It was found that DHCR7 was upregulated in BCa as an independent risk factor, and the expression of DHCR7 was associated with BCa grade and stage, finally resulted in poor prognosis. We further demonstrated that DHCR7 overexpression could accelerate the G0/G1 phase to accelerate the growth of tumor cells, antagonize cell apoptosis, and enhance the invasion and migration capacity, as well as EMT process via PI3K/AKT/mTOR signalling pathway, which could be completely reversed by DHCR7 knockdown. Finally, DHCR7 deficiency significantly decreased tumorigenesis in vivo. Our novel data demonstrated that DHCR7 could modulate BCa tumorigenesis in vitro and in vivo via PI3K/AKT/mTOR signalling pathway. It is suggested that DHCR7 might become a molecular target for the diagnosis and treatment of BCa.


Subject(s)
Proto-Oncogene Proteins c-akt , Urinary Bladder Neoplasms , Animals , Mice , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Oxidoreductases , Mice, Nude , Cell Line, Tumor , Cell Proliferation , TOR Serine-Threonine Kinases/metabolism , Cell Transformation, Neoplastic/metabolism , Carcinogenesis , Urinary Bladder Neoplasms/pathology , Cell Movement , Mammals/metabolism
2.
Acta Med Okayama ; 76(2): 145-154, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35503442

ABSTRACT

With rapidly aging populations, family care functions can become weakened, and community health services often lack unified standards. A standardized and professional community home-based long-term care model (CHLCM) for the elderly is urgently needed in many regions of China and in other countries. Here, we explored the indicators of the need for a CHLCM among elderly individuals, and we constructed a CHLCM. We created and distributed a questionnaire regarding the requirement of long-term care services, based on a literature review. The two-rounds Delphi method was used, involving 20 experts who were randomly selected from among the medical universities, community health service centers, and nursing homes in Nanning, Guangxi, China. The experts' enthusiasm rates in the questionnaire's two rounds were 95% and 100%, respectively. The authentic coefficient of the experts' consulting was 0.857, and that of the experts' academic level was 0.835; the judgement coefficient was 0.880 and the familiar coefficient was 0.855. The CHLCM includes service content and an evaluation. The coordination coefficients for the two primary, eight secondary, and 29 tertiary indicators were 0.200, 0.386, and 0.184, respectively (p<0.05). The experts' enthusiasm and authority were high. The coordination of the experts' agreement was sufficient, and the analysis results were reliable. The CHLCM includes 29 items that provide a foundation and references for the formulation of concrete indicators and subsequent research.


Subject(s)
Long-Term Care , Aged , China , Delphi Technique , Humans , Surveys and Questionnaires
3.
Article in English | MEDLINE | ID: mdl-31354635

ABSTRACT

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis and limited treatment options. Nevertheless, no clinically applicable molecular markers have been identified for the progression of ACCs. DNA methylation alterations were found to contribute to the development of ACC in recent decades. Material and Methods: The aims of the current study was to identify the abnormally methylated differentially expressed genes (DEGs) in ACCs, and to elucidate the mechanistic basis for these changes. Analyses were conducted on gene expression and gene methylation profile datasets to identify the aberrantly methylated DEGs. The DAVID software was used to conduct the analyses of functional enrichment on screened genes. Finally, expression was validated, and the relationship between abnormally methylated DEGs and clinical features was determined via the Oncomine database and The Cancer Genome Atlas (TCGA). To further verify the altered expression and methylation status of our identified genes we also validated these changes at the tissue and cellular levels. Results: We screened and identified 92 differentially expressed genes and 802 abnormally methylated genes. Furthermore, seven aberrantly methylated and dysregulated genes were identified and validated, along with a number of functional enriched pathways. Among these seven genes, the expression or methylation status is significantly correlated with different pathological stages and overall rates of survival. In validation, the expression of seven genes were significantly altered and five genes were hypermethylated in ACC. Conclusions: Our study identified abnormally methylated DEGs and potentially affected pathways in ACCs, from which we could begin to understand the basic molecular mechanisms of these alterations. Moreover, these abnormally methylated genes might serve as therapeutic targets and biomarkers to allow ACC patients to be more precisely diagnosed and effectively treated.

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