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BACKGROUND: Histone lysine demethylases (KDMs) are closely related to the occurrence and development of different tumors through epigenetic mechanisms. However, the prognosis and immune infiltration of KDMs in hepatocellular carcinoma (HCC) remain undefined. METHODS: In the current study, we analyzed the expression of KDMs on HCC patients using the Oncomine, GEPIA, UALCAN, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, Metascape, GSEA, and TIMER databases. Finally, we investigated KDM expression in HCC by qRT-PCR, Western blotting, and IHC. RESULTS: We found that KDM3A/3B/5A/5B and KDM6A were upregulated in HCC patients, while KDM6B and KDM8 were downregulated. The high expressions of KDM1A/2B/3B/5B/5C were markedly related to tumor stages and grades of HCC patients. The abnormal expression of KDM1A/1B/3A/4A/5A/5C/6A/6B/7A and KDM8 were associated with HCC patients' prognosis. Also, we found that HCC tissues presented higher expression levels of KDM1A/2A/5A/5B and lower expression levels of KDM6B. The function of KDMs was primarily related to the histone demethylase activity and cell cycle, p53 signaling pathway, pathways in cancer, transcriptional mis-regulation in cancer, viral carcinogenesis, and FoxO signaling pathway. Furthermore, we indicated that the pathways most involved were the mitotic spindle and DNA repair. Additionally, we found that the expression of KDM1A/1B/3A/4A/5B/5C and KDM6A were significantly correlated with HCC immune infiltration. CONCLUSIONS: Overall, our current results indicated that KDM1A/1B/3A/4A/5B/5C and KDM6A could be novel prognostic biomarkers and provide insights into potential immunotherapy targets to HCC patients.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , PrognósticoRESUMO
We investigate mechanical, structural and electronic properties of CO2 adsorbed graphitic carbon nitride (g-C3N4) system under biaxial tensile strain via first-principles calculations. The results show that the stress of CO2 adsorbed g-C3N4 system increases and then decreases linearly with the increasing biaxial strain, reaching maximum at 0.12 strain. This is primarily caused by the plane N-C stretching of the g-C3N4. Furthermore, both the Perdew-Burke-Ernzerhof (PBE) and Heyd- Scuseria-Ernzerhof screened hybrid functional (HSE06) band gaps show direct-indirect transitions under biaxial tensile strain and have the maximum also at 0.12 strain. It is found that there is large dipole transition matrix element around Γ point, leading high optical absorption coefficients of the deformed adsorption system, which would be of great use for the applications of new elastic nanoelectronic and optoelectronic devices.
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We report first-principles calculations on the structural, mechanical, and electronic properties of O2 molecule adsorption on different graphenes (including pristine graphene (G-O2), N(nitrogen)/B(boron)-doped graphene (G-N/B-O2), and defective graphene (G-D-O2)) under equibiaxial strain. Our calculation results reveal that G-D-O2 possesses the highest binding energy, indicating that it owns the highest stability. Moreover, the stabilities of the four structures are enhanced enormously by the compressive strain larger than 2%. In addition, the band gaps of G-O2 and G-D-O2 exhibit direct and indirect transitions. Our work aims to control the graphene-based structure and electronic properties via strain engineering, which will provide implications for the application of new elastic semiconductor devices.
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Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS.
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Dislipidemias/epidemiologia , Hiperandrogenismo/epidemiologia , Hipolipemiantes/uso terapêutico , Resistência à Insulina/fisiologia , Síndrome do Ovário Policístico/epidemiologia , Adulto , Comorbidade , Dislipidemias/diagnóstico , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperandrogenismo/diagnóstico , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/diagnóstico , Prevalência , Prognóstico , Medição de RiscoRESUMO
The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions. mTOR allows cancer cells to escape the normal biochemical system and regulates the balance between apoptosis and survival. Some recent studies have suggested that involvement of the mTOR signaling system is an important pathophysiological basis of PCOS. Overexpression of the mTOR pathway can impair the interaction of cumulus cells, lead to insulin resistance, and affect the growth of follicles directly. The roles of mTOR signaling in follicular development have been extensively studied in recent years; abnormalities in this process lead to a series of pathologies such as POF and infertility. To improve understanding of the role of the mTOR signaling pathway in the pathogenesis and development of ovarian diseases, here we review the roles of mTOR signaling in such diseases and discuss the corresponding therapeutic strategies that target this pathway. Clin. Anat. 31:891-898, 2018. © 2018 Wiley Periodicals, Inc.