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RATIONALE: Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood. METHODS AND RESULTS: Using osteoblast MR knockout (MRobko) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MRobko mice compared to littermate control (MRfl/fl) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MRobko mice compared to MRfl/fl mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients. CONCLUSIONS: MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.
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Insuficiencia Cardíaca , Infarto del Miocardio , Animales , Humanos , Ratones , Antagonistas de Receptores de Mineralocorticoides/farmacología , Infarto del Miocardio/patología , Osteoblastos/metabolismo , Espironolactona , Remodelación VentricularRESUMEN
Seven undescribed withanolides (1-7) and six artificial withanolides (8-13), along with 20 known compounds (14-33) were isolated from the aerial parts of Tubocapsicum anomalum. Their structures were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray crystallography. All isolates were evaluated for their antiproliferative effects against five human tumor cell lines (Hep3B, MDA-MB-231, SW480, HCT116 and A549), among which compound 24 (tubocapsanolide A) exhibited the highest activities against the MDA-MB-231 cells with an IC50 value of 1.89 ± 1.03 µM. Further studies showed that 24 exhibited significant damage to mitochondria in MDA-MB-231 cells, including excess reactive oxygen species, decreased mitochondrial membrane potential, and apoptosis initiation. In addition, compound 24 also inhibited cell migration. These findings show that tubocapsanolide A may be a promising molecule for triple-negative breast cancer treatment and merit further evaluation.
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Antineoplásicos Fitogénicos/farmacología , Extractos Vegetales/farmacología , Solanaceae/química , Witanólidos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Conformación Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Relación Estructura-Actividad , Células Tumorales Cultivadas , Witanólidos/química , Witanólidos/aislamiento & purificaciónRESUMEN
BACKGROUND: Endometrial cancer (EC) is one of the three major gynecological malignancies. Numerous biomarkers that may be associated with survival and prognosis have been identified through database mining in previous studies. However, the predictive ability of single-gene biomarkers is not sufficiently specific. Genetic signatures may be an improved option for prediction. This study aimed to explore data from The Cancer Genome Atlas (TCGA) to identify a new genetic signature for predicting the prognosis of EC. METHODS: mRNA expression profiling was performed in a group of patients with EC (n = 548) from TCGA. Gene set enrichment analysis was performed to identify gene sets that were significantly different between EC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Quantitative real-time-PCR was used to verify the reliability of the expression of selected mRNAs. Subsequent multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan-Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. RESULT: Nine genes associated with glycolysis (CLDN9, B4GALT1, GMPPB, B4GALT4, AK4, CHST6, PC, GPC1, and SRD5A3) were found to be significantly related to overall survival. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. Based on the nine-gene signature, the 548 patients with EC were divided into high/low-risk subgroups. The prognostic ability of the nine-gene signature was not affected by other factors. CONCLUSION: A nine-gene signature associated with cellular glycolysis for predicting the survival of patients with EC was developed. The findings provide insight into the mechanisms of cellular glycolysis and identification of patients with poor prognosis in EC.
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RESEARCH QUESTION: What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? DESIGN: Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). RESULTS: It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. CONCLUSIONS: These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS.
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Betaína-Homocisteína S-Metiltransferasa/metabolismo , Cistationina betasintasa/metabolismo , Homocisteína/sangre , Hiperhomocisteinemia/etiología , Hígado/metabolismo , Síndrome del Ovario Poliquístico/complicaciones , Animales , Modelos Animales de Enfermedad , Femenino , Hiperhomocisteinemia/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , RatasRESUMEN
Stem cells play a critical role in endometrial cancer progression. However, the current methodologies used to isolate endometrial cancer stem cells (ECSCs) remain unsatisfactory. The ECSCs were isolated by serumfree suspension cultivation. The stem cells-related genes CD44, CD133, Oct4, Sox2 and Nanog were analyzed, and the biological behaviour of ECSCs was evaluated in vitro and vivo. The results suggest that (i) serumfree suspension cultivation is non-toxic and a convenient way for isolating the ECSCs, and is not limited to specific surface markers; (ii) Ishikawa cells can be used as an effective source of ECSCs, and the obtained ECSCs expressing the pluripotent stem cells markers CD44, CD133, Oct4, Sox2, and Nanog; (iii) ECSCs originated from Ishikawa cells showed an increased ability to invasion and metastasis in vitro, and exhibited a high proliferative capacity and pluripotency in vivo and vitro. These findings indicate that serumfree suspension cultivation is an effective method for isolating ECSCs from Ishikawa cells, and the obtained ECSCs are tumorigenic and display stem cell-like properties.
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Neoplasias Endometriales/patología , Endometrio/patología , Células Madre Neoplásicas/patología , Antígeno AC133/análisis , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Separación Celular , Supervivencia Celular , Endometrio/citología , Femenino , Humanos , Receptores de Hialuranos/análisis , Ratones Endogámicos BALB C , Células Madre Neoplásicas/citología , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/patologíaRESUMEN
BACKGROUND: The receptor for advanced glycation endproducts (RAGE) and microvascular status both play a critical role in cancer progression. However, the crosstalk between RAGE and microvascular formation in endometrial cancer remains largely unknown. METHODS: RAGE expression and microvessel density were examined in 20 cases of normal endometrial tissue, 37 cases of well-differentiated endometrial cancer tissue, and 35 cases of poorly-differentiated endometrial cancer tissue. Regression analysis was used to examine the relationship between RAGE and microvessel density. The knockdown of RAGE was achieved using a small interfering RNA in HEC-1A endometrial cancer cells. A xenografted tumour model was used to evaluate RAGE-mediated microvascular formation and proliferation of endometrial cancer cells. RESULTS: It was shown that (i) RAGE expression gradually increased in normal endometrium, well-differentiated endometrial cancer, and poorly-differentiated endometrial cancer, respectively; (ii) a positive correlation existed between RAGE and microvessel density in human endometrial cancer samples; (iii) RAGE knockdown was effective in decreasing microvessel formation in xenografted tumour models; and (iv) RAGE knockdown can significantly inhibit the proliferation of endometrial cancer cells in vivo. CONCLUSIONS: These results indicate that RAGE may be a potential trigger in microvascular formation and proliferation in the development of endometrial cancer.
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Proliferación Celular/genética , Neoplasias Endometriales/genética , Microvasos/patología , Receptor para Productos Finales de Glicación Avanzada/genética , Anciano , Animales , Línea Celular Tumoral , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Microvasos/metabolismo , Persona de Mediana Edad , Receptor para Productos Finales de Glicación Avanzada/biosíntesis , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin-leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case-control and eight case-control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34-0.65; I(2) = 63.7%; n = 13), 2.19 (95% CI: 1.44-3.31; I(2) = 64.2%; n = 7),and 0.45 (95% CI: 0.24-0.86; I(2) = 90.1%; n = 5), respectively. Notably, there was an 18% reduction in risk for per each 5 µg/mL increment in circulating adiponectin concentrations (SOR = 0.82; 95% CI: 0.74-0.90; I(2) = 49%; n = 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this meta-analysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.
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Adiponectina/sangre , Neoplasias Endometriales/epidemiología , Leptina/sangre , Bases de Datos Bibliográficas , Neoplasias Endometriales/sangre , Femenino , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Endometrial cancer (EC) cells exhibit abnormal glucose metabolism, characterized by increased aerobic glycolysis and decreased oxidative phosphorylation. Targeting cellular glucose metabolism in these cells could be an effective therapeutic approach for EC. This study aimed to assess the roles of LIN28B, PCAT5, and IGF2BP3 in the glucose metabolism, proliferation, migration, and invasion of EC cells. LIN28B highly expressed in EC, binds and stabilizes PCAT5. PCAT5, overexpressed in EC, and its 1485-2288nt region can bind to the KH1-2 domain of IGF2BP3 to prevent MKRN2 from binding to the K294 ubiquitination site of IGF2BP3, thus stabilizing IGF2BP3. Finally, IGF2BP3 promotes the aerobic glycolysis, proliferation, migration and invasion of EC cells by stabilizing the key enzymes of glucose metabolism HK2 and PKM2. Taken together, our data reveal that the LIN28B/PCAT5/IGF2BP3 axis is critical for glucose reprogramming and malignant biological behavior in EC cells. Therefore, targeting this axis may contribute to the development of a novel therapeutic strategy for EC metabolism.
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Neoplasias Endometriales , Glucólisis , Femenino , Humanos , Línea Celular Tumoral , Glucólisis/genética , Neoplasias Endometriales/genética , Fosforilación Oxidativa , Glucosa/metabolismo , Proliferación Celular/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
Endometrial cancer (EC) stem cells (ECSCs) are pivotal in the oncogenesis, metastasis, immune escape, chemoresistance, and recurrence of EC. However, the specific mechanism of stem cell maintenance in EC cells (ECCs) has not been clarified. We found that WTAP and m6A levels decreased in both EC and ECSCs, and that knocking down WTAP promoted ECCs and ECSCs properties, including proliferation, invasion, migration, cisplatin resistance, and self-renewal. The downregulation of WTAP leads to a decrease in the m6A modification of EGR1 mRNA, and it is difficult for IGF2BP3, as an m6A reader, to recognize and bind to EGR1 mRNA that has lost m6A modification, resulting in a decrease in the stability of EGR1 mRNA. A decrease in the EGR1 level led to a decrease of in the expression tumor suppressor gene PTEN, resulting in deregulation and loss of cellular homeostasis and thereby fostering EC stem cell traits. Notably, the enforced overexpression of WTAP, EGR1, and PTEN inhibited the oncogenic effects of ECCs and ECSCs in vivo, and the combined overexpression of WTAP + EGR1 and EGR1 + PTEN further diminished the tumorigenic potential of these cells. Our findings revealed that the WTAP/EGR1/PTEN pathway is important regulator of EC stem cell maintenance, chemotherapeutic resistance, and tumorigenesis, suggesting a novel and promising therapeutic avenue for treating EC.
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Proteína 1 de la Respuesta de Crecimiento Precoz , Neoplasias Endometriales , Células Madre Neoplásicas , Fosfohidrolasa PTEN , Proteínas de Unión al ARN , Humanos , Femenino , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Ratones , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Línea Celular Tumoral , Fenotipo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Adenosina/análogos & derivados , Adenosina/metabolismoRESUMEN
Rectal neuroendocrine tumors (rNETs) measuring less than 10 mm in diameter are defined as small rNETs. Due to the low risk of distant invasion and metastasis, endoscopic treatments, including modified endoscopic mucosal resection, endoscopic submucosal dissection, and other transanal surgical procedures, are effective. This review article proposes a follow-up plan according to the size and histopathology of the tumor after operation.
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BACKGROUND: Mineralocorticoid receptor (MR) antagonists have been widely used to treat heart failure (HF). Studies have shown that MR in T cells plays important roles in hypertension and myocardial hypertrophy. However, the function of T-cell MR in myocardial infarction (MI) has not been elucidated. METHODS: In this study, we used T-cell MR knockout (TMRKO) mouse to investigate the effects of T-cell MR deficiency on MI and to explore the underlying mechanisms. Echocardiography and tissue staining were used to assess cardiac function, fibrosis, and myocardial apoptosis after MI. Flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect immune cell infiltration and inflammation. RESULTS: T-cell MR deficiency significantly improved cardiac function, promoted myocardial repair, and inhibited myocardial apoptosis, fibrosis, and inflammation after MI. Luminex assays revealed that TMRKO mice had significantly lower levels of interferon-gamma (IFN-γ) and interleukin-6 (IL-6) in serum and infarcted myocardium than littermate control mice. In cultured splenic T cells, MR deficiency suppressed IL-6 expression, whereas MR overexpression enhanced IL-6 expression. Chromatin immunoprecipitation (ChIP) assay demonstrated that MR bound to the MR response element on the promoter of IL-6 gene. Finally, T-cell MR deficiency significantly suppressed accumulation of macrophages in infarcted myocardium and differentiation of proinflammatory macrophages, thereby alleviating the consequences of MI. CONCLUSIONS: T-cell MR deficiency improved pathologic ventricular remodelling after MI, likely through inhibition of accumulation and differentiation of proinflammatory macrophages. At the molecular level, MR may work through IFN-γ and IL-6 in T cells to exert functions in MI.
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Interleucina-6 , Infarto del Miocardio , Ratones , Animales , Remodelación Ventricular , Receptores de Mineralocorticoides/genética , Infarto del Miocardio/metabolismo , Miocardio/patología , Linfocitos T/metabolismo , Interferón gamma , Fibrosis , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.
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Carcinoma Endometrioide , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/genética , Neoplasias Ováricas/metabolismo , Proteómica , Carcinoma Endometrioide/metabolismo , Transducción de Señal , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proteínas de la MembranaRESUMEN
Microglia/macrophage activation plays an essential role in Ischemic stroke (IS). Nuclear receptor corepressor 1 (NCoR1) has been identified as a vital regulator in macrophages. The present study aims to explore the functions of macrophage NCoR1 in IS. Macrophage NCoR1 knockout (MNKO) mice and littermate control mice were subjected to middle cerebral artery occlusion (MCAO). Our data showed that macrophage NCoR1 deficiency significantly reduced the infarct size and infarct volume as well as brain edema after MCAO. Additionally, MNKO induced less microglia/macrophage infiltration and activation, neuroinflammation, apoptosis of neuronal cells, and BBB disruption in brains after IS. Mechanistic studies revealed that NCoR1 interacted with LXRß in microglia and MNKO impaired the activation of the Nuclear factor-κB signaling pathway in brains after IS. Our data demonstrated that macrophage NCoR1 deficiency inhibited microglia/macrophage activation and protected against IS. Targeting NCoR1 in microglia/macrophage may be a potential approach for IS treatment.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , Ratones Endogámicos C57BL , Macrófagos/metabolismo , Infarto de la Arteria Cerebral Media/genética , Ratones Noqueados , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/prevención & control , Co-Represor 1 de Receptor Nuclear/genéticaRESUMEN
N6-methyladenosine (m6A) RNA methylation is associated with malignant tumor progression and is modulated by various m6A RNA methylation regulator proteins. However, its role in endometrial cancer is unclear. In this work, we analyzed sequence, copy number variation, and clinical data obtained from the TCGA database. Expression was validated using real-time quantitative polymerase chain reaction and immunohistochemistry. Changes in m6A RNA methylation regulators were closely related to the clinicopathological stage and prognosis of endometrial cancer. In particular, ZC3H13, YTHDC1, and METTL14 were identified as potential markers for endometrial cancer diagnosis and prognosis. The TIMER algorithm indicated that immune cell infiltration correlated with changes in ZC3H13, YTHDC1, and METTL14 expression. Meanwhile, ZC3H13 or YTHDC1 knockdown promoted the proliferation and invasion of endometrial cancer cells. Through gene enrichment analysis, we constructed a regulatory network in order to explore the potential molecular mechanism involving ZC3H13, YTHDC1, and METTL14. Virtual screening predicted interactions of potential therapeutic compounds with METTL14 and YTHDC1. These findings advance the understanding of RNA epigenetic modifications in endometrial cancer while identifying m6A regulators associated with immune infiltration, prognosis, and potential treatment strategies.
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Adenosina/análogos & derivados , Neoplasias Endometriales/genética , Neoplasias Endometriales/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Adenosina/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Variaciones en el Número de Copia de ADN/genética , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Ligandos , Metilación , Persona de Mediana Edad , Simulación del Acoplamiento Molecular , Mutación/genética , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Microambiente Tumoral/inmunologíaRESUMEN
The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.
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Epithelial-mesenchymal transition (EMT) promotes tumorigenesis and metastasis and increases tumor tolerance to treatment intervention. Abnormal activation of transforming growth factor ß (TGF-ß) and Wnt pathway induces EMT. Long non-coding RNAs (lncRNAs) significantly influence EMT regulation. Herein, we show that MIR210HG is overexpressed in endometrial cancer tissues, which is associated with poor prognosis. MIR210HG silencing significantly inhibited proliferation, migration, invasion, and EMT phenotype formation in vitro as well as tumorigenesis in vivo. Mechanistically, bioinformatics analyses, RNA binding protein immunoprecipitation (RIP) assays, and luciferase assays showed that MIR210HG acts as a molecular sponge of miR-337-3p and miR-137 to regulate the expression of HMGA2. Additionally, MIR210HG overexpression significantly enriched the Wnt/ß-catenin and TGF-ß/Smad3 signaling pathway genes, while MIR210HG or HMGA2 knockdown suppressed the Wnt/ß-catenin and TGF-ß/Smad3 signaling pathway. Our findings on the MIR210HG-miR-337-3p/137-HMGA2 axis illustrate its potential as a target for endometrial cancer therapeutic development.
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PURPOSE: To explore the effect of chronic kidney disease on the composition of oral microbial community in mice and find the significant species. METHODS: Twenty C57BL/6 male mice were randomly divided into 4 groups: healthy control group (HC), periodontitis group (PD), chronic kidney disease group (CKD) and chronic kidney disease and periodontitis group (CKD+PD). The periodontitis model was created in the fourth week when the chronic kidney disease model was established, and then the mice were sacrificed in the sixth week. Histopathological analysis of the kidney was performed by H-E staining and Masson's trichrome staining. Alveolar bone resorption of maxilla was analyzed by micro-CT analysis. The third-generation full-length sequencing of 16SrRNA gene was used to analyze the composition of oral microbial community among groups. Statistical analysis was performed using SPSS 24.0 software package. RESULTS: There were significant differences in alveolar bone resorption, the richness of species and the overall composition of the microbial community among the four groups (Pï¼0.001). In CKD group, Streptococcus azizii had the most significant abundance. Escherichia coli was the most significantly different species among identifiable bacteria in CKD+PD group, while Staphylococcus lentus and Lactobacillus murinus were species with the most significant differences in HC group and PD group, respectively. CONCLUSIONS: The composition of the oral microbial community was significantly different among four groups with significant species.
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Pérdida de Hueso Alveolar , Periodontitis , Insuficiencia Renal Crónica , Animales , Masculino , Maxilar/patología , Ratones , Ratones Endogámicos C57BL , Insuficiencia Renal Crónica/patologíaRESUMEN
PURPOSE: The evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk. MATERIALS AND METHODS: The online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger's and Begg's tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a randomeffects model. RESULTS: Five prospective studies (four cohort studies and one casecohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No signiï¬cant publication bias was detected. CONCLUSION: This study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.
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Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/prevención & control , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Rheumatic heart disease refers to the long-term damage of heart valves and results from an autoimmune response to group A Streptococcus infection. This study aimed to analyze the microbiota composition of patients with rheumatic heart disease and explore potential function of microbiota in this disease. First, we revealed significant alterations of microbiota in feces, subgingival plaques, and saliva of the patients compared to control subjects using 16S rRNA gene sequencing. Significantly different microbial diversity was observed in all three types of samples between the patients and control subjects. In the gut, the patients possessed higher levels of genera including Bifidobacterium and Eubacterium, and lower levels of genera including Lachnospira, Bacteroides, and Faecalibacterium. Coprococcus was identified as a super-generalist in fecal samples of the patients. Significant alterations were also observed in microbiota of subgingival plaques and saliva of the patients compared to control subjects. Second, we analyzed microbiota in mitral valves of the patients and identified microbes that could potentially transmit from the gut or oral cavity to heart valves, including Streptococcus. Third, we further analyzed the data using random forest model and demonstrated that microbiota in the gut, subgingival plaque or saliva could distinguish the patients from control subjects. Finally, we identified gut/oral microbes that significantly correlated with clinical indices of rheumatic heart disease. In conclusion, patients with rheumatic heart disease manifested important alterations in microbiota that might distinguish the patients from control subjects and correlated with severity of this disease.
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Microbioma Gastrointestinal , Microbiota , Cardiopatía Reumática , Heces , Humanos , Válvula Mitral , Boca , ARN Ribosómico 16SRESUMEN
BACKGROUND: Choriocarcinoma is a highly malignant trophoblastic tumor that presents with early symptoms similar to those of an ectopic pregnancy. Here we present a patient with suspected ectopic pregnancy diagnosed by laparoscopic surgery in our hospital. The patient was found to have choriocarcinoma that had metastasized to the lumbar muscle and presented with symptoms similar to those of an ectopic pregnancy. CASE SUMMARY: The patient was a 34-year-old female who complained of amenorrhea lasting 53 d, 7 d of right lower back pain, and 3 d of right lower abdominal pain. Transvaginal ultrasonography revealed the absence of a gestational sac in the uterus and a mass in the left adnexa. After 6 d of re-examination, ultrasound and computed tomography (CT) examination were performed on the mass located in the left adnexa area. We also noted that the patient's serum ß-human chorionic gonadotropin (hCG) level was increased. Considering an ectopic pregnancy, we performed a laparoscopy and hysteroscopy. During the operation, a left ovarian mixed echogenic mass approximately 2.5 cm × 2.0 cm with no villous tissue was found. Postoperative levels of serum hCG continued to increase. Lung CT examination showed lung nodules. Both CT and magnetic resonance imaging showed a mixed echogenic mass in the lumbar muscle. Considering lumbar metastasis of choriocarcinoma, six courses of cisplatin, dactinomycin, and etoposide chemotherapy were given after surgery. The patient's serum ß-hCG level decreased to normal and the mixed echogenic mass in the lumbar muscle decreased in size after the fifth course of chemotherapy. All symptoms subsequently disappeared after treatment. CONCLUSION: In summary, lumbar metastasis from choriocarcinoma is extremely rare. Appropriate chemotherapy can successfully treat these metastasized tumors.