RESUMEN
MiR-1283 has been identified as a tumor suppressor in some malignancies. Whereas, the role of miR-1283 in HER2-positive (HER2+) breast cancer, particularly its role in regulating cell proliferation, one of the most significant features of tumor progression, is unclear. The related microRNA screened by the breast cancer sample GSE131599 dataset were detected in HER2+ breast cancer tissues and cell lines. Then, the obtained miR-1283 was overexpressed in SKBR3 and BT-474 cells followed by relevant functional assays concerning cell proliferation and apoptosis. The xenograft mouse model was induced and the effect of miR-1283 on tumor growth and cell proliferation was examined. The target of miR-1283 and the transcription factor regulating miR-1283 were predicted and identified. Finally, the influence of transcription factor KLF14 on cell proliferation and apoptosis was investigated. An integrated analysis confirmed that miR-1283 expression was significantly decreased in HER2+ breast cancer tissues. Also, by q-RT-PCR detection, miR-1283 expression was markedly reduced in HER2+ breast cancer tissues and cell lines. The miR-1283 overexpression prevented the proliferation and enhanced apoptosis of HER2+ breast cancer cells, as well as inhibited tumor growth. Mechanistically, miR-1283 inhibited TFAP2C expression by targeting the 3'-untranslated regions of TFAP2C messenger RNA, and the KLF14 enhanced miR-1283 level via binding to its promoter. The result subsequently confirmed the KLF14/miR-1283 signaling suppressed cell proliferation in HER2+ breast cancer. Our results suggested that the KLF14/miR-1283/TFAP2C axis inhibited HER2+ breast cancer progression, which might provide novel insight into mechanical exploration for this disease.
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Neoplasias de la Mama , MicroARNs , Humanos , Animales , Ratones , Femenino , Línea Celular Tumoral , Neoplasias de la Mama/metabolismo , MicroARNs/metabolismo , Proliferación Celular/genética , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Factor de Transcripción AP-2/genéticaRESUMEN
BACKGROUND: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. OBJECTIVES: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. METHODS: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FINDINGS: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. CONCLUSION: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Flavanonas , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Farmacología en Red , Fosfatidilinositol 3-QuinasasRESUMEN
Anhedonia is the core symptom of depression, which largely reflects the therapeutic effect of depression. Hypericum perforatum is one of the most important antidepressant herb that has fewer side effects than traditional antidepressants. Considering the antibacterial effect of Hypericum perforatum, we verified whether this antidepressant activity was related to intestinal microbiomics. So we established anhedonia mouse model to explore the underlying treatment mechanism of hyperforin, the key antidepressant ingredient of Hypericum perforatum and to screen new psychobiotics based on hyperforin. It was found that hyperforin prevented anhedonia induced by chronic restraint stress in mice and altered the richness and evenness of bacteria populations compared with stressed mice. Metastat analysis showed that Akkermansia muciniphila and Muribaculum intestinale were the bacterial species obviously affected by hyperforin, and their abundance in hyperforin-treated group significantly increased. The results suggest that the effect of hyperforin on anhedonia may be partly assisted by Akkermansia muciniphila. These also indicate that Muribaculum intestinale may be another important intestinal bacteria involved in the pathogenesis of anhedonia symptom and depression.
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Microbioma Gastrointestinal , Hypericum , Animales , Ratones , Anhedonia , Extractos Vegetales/farmacología , Compuestos Bicíclicos con Puentes/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Fenotipo , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.
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Neoplasias de la Mama , MicroARNs , Neoplasias de la Mama/genética , Proliferación Celular , Femenino , Humanos , Hibridación Fluorescente in Situ , MicroARNs/genética , ARN Circular , Receptor ErbB-2/genéticaRESUMEN
BACKGROUND: Coronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis. METHODS: We searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software. RESULTS: Six studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223-1.813). Further, MIF -173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365-2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003-1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele. CONCLUSIONS: We found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.
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Enfermedad de la Arteria Coronaria/genética , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Polimorfismo de Nucleótido Simple , Pueblo Asiatico/genética , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etnología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Estudios Observacionales como Asunto , Medición de Riesgo , Población Blanca/genéticaRESUMEN
BACKGROUND: Lysimachia christinae Hance is a traditional Chinese medicine with diuretic, detumescent, and detoxifying effects. Our aimed to optimize the extraction protocol to maximize the yield of flavonoids from Lysimachia christinae Hance, and evaluate the pharmacological activities of four fractions, namely, petroleum ether (PE), ethyl acetate (EA), n-butanol (NB), and aqueous (AQ) fractions, of the ethanolic extract of Lysimachia christinae Hance. METHODS: The flavonoid monomers in the crude extract were characterized via high performance liquid chromatography (HPLC), were used as markers for extract quality control and standardization. The total flavonoid, total phenolic, and total polysaccharide contents of each fraction were determined by spectrophotometry. Further, the in vitro free radical (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), superoxide, and hydroxyl radicals) scavenging activities, and antioxidant capacity in endothelial cells were evaluated for each fraction. RESULTS: After optimizing the extraction protocol to maximize the total flavonoid yield from L. christinae Hance, the NB fractions had the highest total flavonoid (39.4 ± 4.55 mg RE/g), total phenolic (41.1 ± 3.07 mg GAE/g) and total polysaccharide (168.1 ± 7.07 mg GE/g); In addition, the NB fraction of the ethanolic extract of L. christinae Hance reveal the strongest radical-scavenging activity, antioxidant activity and protective effects against H2O2-induced injury in HUVECs. CONCLUSIONS: Among the four fractions of L. christinae Hance, the NB fraction showed the most potent antioxidant and endothelial protective effects, which may be attributed to its high flavonoid, phenolic contents and optimal portfolio of different active ingredients of NB fractions of the ethanolic extract of L. christinae Hance. This study might improve our understanding of the pharmacological activities of L. christinae Hance, thereby facilitating its use in disease prevention and treatment.
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Antioxidantes , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Primulaceae/química , Antioxidantes/química , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Flavonoides/análisis , Células Endoteliales de la Vena Umbilical Humana , Humanos , Fenoles/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polisacáridos/análisisRESUMEN
BACKGROUND: Chromosomal disorders in non obstructive azoospermia (NOA) may have an important influence on spermatogenesis, which may be reflected by the serum inhibin B levels. Till now, few studies have concerned the relationship of genetic causes and inhibin B in NOA. METHODS: In this retrospective study, 322 men with NOA in Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University were collected. The level of follicle stimulating hormone (FSH), inhibin B, Y chromosome microdeletion test (YCMD) and karyotype were measured. RESULTS: Abnormal karyotypes were present in 38.5% of NOA, and YCMD were present in 18.0%, there was a high correlation between karyotypes and YCMD (χ2 = 11.892, P < 0.001). The level of inhibin B in chromosomal abnormality from lowest to highest was 46,XX (or 45,X), 47, XXY, mosaics, polymorphisms, inversion and translocation. And the level of inhibin B within Non-AZF a&b region deletion was higher than AZF a&b microdeletion. CONCLUSION: According to the level of inhibin B, spermatogenesis in chromosomal abnormality from lowest to highest was 46,XX (or 45,X), 47, XXY, mosaics, polymorphisms, inversion and translocation. And spermatogenesis within Non-AZF a&b region deletion was better than AZF a&b microdeletion.
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Azoospermia/genética , Inhibinas/sangre , Adulto , Azoospermia/sangre , Deleción Cromosómica , Cromosomas Humanos Y , Hormona Folículo Estimulante , Humanos , Cariotipificación , Masculino , Estudios Retrospectivos , Aberraciones Cromosómicas Sexuales , Espermatogénesis/genéticaRESUMEN
BACKGROUND/AIMS: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. METHODS: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF(V600E) mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. RESULTS: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF(V600E) mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF(V600E) mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF(V600E) mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). CONCLUSION: This meta-analysis confirmed significant associations between BRAF(V600E) mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF(V600E) mutation for PTC prognosis.
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Carcinoma/genética , Carcinoma/patología , Mutación Puntual , Proteínas Proto-Oncogénicas B-raf/genética , Glándula Tiroides/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Factores de Edad , Carcinoma/diagnóstico , Carcinoma/epidemiología , Carcinoma Papilar , Femenino , Humanos , Metástasis Linfática/diagnóstico , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores Sexuales , Cáncer Papilar Tiroideo , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiologíaRESUMEN
OBJECTIVES: The aim of this study was to evaluate the impact of mean platelet volume (MPV) on the intracoronary thrombus burden and short-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Platelets play a crucial role in the pathophysiology of coronary artery disease. MPV has been reported to be an indicator of platelet reactivity. METHODS: A total of 649 consecutive STEMI patients who underwent primary PCI between January 2008 and December 2013 were enrolled and divided into two groups based on the thrombus burden: the large thrombus burden (LTB) group and the small thrombus burden (STB) group. The primary endpoint was all-cause mortality at 30 days. RESULT: The LTB group had significantly higher admission MPV compared with the STB group (10.77 ± 1.22 vs. 9.95 ± 1.03, P < 0.001). The cumulative 30-day all-cause mortality rate was significantly higher in the groups with high MPV and LTB (9.8% vs. 2.5%, P < 0.001, 8.6% vs. 4.1%, P = 0.036, respectively). In a receiver operating characteristics analysis, MPV ≥ 10.2 predicted LTB with 73.5% sensitivity and 68.9% specificity. Multivariate logistic regression analysis demonstrated MPV was an independent predictor of large intracoronary thrombus burden (OR 1.794, 95% CI 1.533 to 2.100, P < 0.001) and 30-day all-cause mortality (HR 1.408, 95% CI 1.040 to 1.906, P = 0.027). CONCLUSIONS: Increased MPV at admission is an independent predictor of large intracoronary thrombus burden and short-term mortality. It may be a useful biomarker for risk stratification in patients with STEMI undergoing primary PCI. © 2015 Wiley Periodicals, Inc.
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Angiografía Coronaria , Trombosis Coronaria/terapia , Volúmen Plaquetario Medio , Infarto del Miocardio/sangre , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/mortalidad , Anciano , Área Bajo la Curva , Distribución de Chi-Cuadrado , Trombosis Coronaria/sangre , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/mortalidad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Selección de Paciente , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
New Onset Diabetes after Transplantation (NODAT) is defined as sustained hyperglycemia developing in patients without diabetes history before transplantation. A cohort study was performed to access the effects of tacrolimus on insulin secretion and insulin sensitivity and consequently in the development of NODAT in kidney transplant recipients. Then, we further investigated the association between NODAT and single-nucleotide polymorphisms of IRS-1 and IRS-2 in renal allograft recipients. One hundred and fifty-eight kidney transplant patients, receiving tacrolimus as the base immunosuppressant, were divided into two groups: with or without NODAT. Plasma levels of fasting insulin concentration (FINS) and C-peptide were determined by enhanced chemiluminescence immunoassay and ADVIA Centaur C peptide assay, respectively. The genotypes of Gly1057Asp in IRS-2 and Gly972Arg in IRS-1 were detected through polymerase chain reaction fragment length polymorphism in NODAT and non-NODAT patients. It was found that the concentrations of fasting plasma insulin and C-peptide in NODAT and non-NODAT patients treated with tacrolimus were higher than that in healthy volunteers (p < 0.05). Fasting plasma insulin concentration in NODAT was significantly elevated compared with than that in non-NODAT group (p < 0.05). But there are no statistical differences in fasting plasma C-peptide concentrations between NODAT and non-NODAT groups. The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg in NODAT patients were not significantly different from non-NODAT patients (p > 0.05). In conclusion, insulin resistance is the primary cause of tacrolimus-induced NODAT. The IRS-2 Gly1057Asp and IRS-1 Gly972Arg genotypes are not related to NODAT.
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Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/epidemiología , Ayuno/sangre , Resistencia a la Insulina , Insulina/sangre , Trasplante de Riñón , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/epidemiología , Tacrolimus/efectos adversos , Adulto , Estudios de Cohortes , Diabetes Mellitus/genética , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores , Masculino , Complicaciones Posoperatorias/genética , Factores de Riesgo , Factores de TiempoRESUMEN
Objective: Coronary artery disease (CAD) is a the most common type of heart disease, and is associated with the highest mortality rate. The role of the ß3-adrenergic receptor gene (ADRB3) in energy homeostasis and lipolysis suggests that it may be associated with obesity, insulin resistance, diabetes, and hypertension. Herein, we sought to examine the relationship between CAD and variants of the ADRB3 gene in individuals with Han and Uygur ethnicities in China. Methods: All 1022 participants were genotyped for two ADRB3 single nucleotide polymorphisms (SNPs; rs1892818 and rs9693898) using real-time polymerase chain reaction (TaqMan). Uygur (259 CAD patients, 161 control group) and Han (308 CAD patients, 294 control group) were included in two case-control studies. We subsequently developed a predictive model using ADRB3 genetic variation and clinical variables to predict risk of CAD. Results: The rs1892818 CT genotype (8.5% vs 3.9%, p = 0.019) and T allele (4.3% vs 1.9%, p = 0.021) were more frequently detected in the control subjects compared to CAD patients of the Han population but not in the Uygur population. The rs9693898 was not associated with CAD in either ethnic population. Logistic regression analysis further demonstrated that carriers of the rs1892818 CT genotype had a lower risk of CAD than did those with the CC genotype (CT vs CC, p = 0.044, odds ratio [OR] = 0.441, 95% confidence interval [CI]: 0.199-0.976). Using this data, we constructed a predictive nomogram model for CAD with an area under the curve (95% CI) of 0.722 (0.682, 0.761). Conclusions: Our results suggest that rs1892818 is associated with CAD in the Han population and that the CT genotype of rs1892818 may serve as a protective factor for CAD in Han individuals. The proposed nomograms can be used for the prediction of CAD in this population.
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Enfermedad de la Arteria Coronaria , Receptores Adrenérgicos beta 3 , Humanos , Estudios de Casos y Controles , China , Enfermedad de la Arteria Coronaria/genética , Pueblos del Este de Asia/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Nomogramas , Polimorfismo de Nucleótido Simple , Receptores Adrenérgicos beta 3/genética , Factores de RiesgoRESUMEN
The sigma-1 receptor (Sig-1R) is encoded by the SIGMAR1 gene and is a nonopioid transmembrane receptor located in the mitochondrial-associated endoplasmic reticulum membrane (MAM). It helps to locate endoplasmic reticulum calcium channels, regulates calcium homeostasis, and acts as a molecular chaperone to control cell fate and participate in signal transduction. It plays an important role in protecting neurons through a variety of signaling pathways and participates in the regulation of cognition and motor behavior closely related to neurodegenerative diseases. Based on its neuroprotective effects, Sig-1R has now become a breakthrough target for alleviating Alzheimer's disease and other neurodegenerative diseases. This article reviews the most cutting-edge research on the function of Sig-1R under normal or pathologic conditions and target drugs of the sigma-1 receptor in neurodegenerative diseases.
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Proteínas del Tejido Nervioso/agonistas , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Receptores sigma/agonistas , Animales , Autofagia , Bulimia/tratamiento farmacológico , Bulimia/fisiopatología , Calcio/metabolismo , Cognición/efectos de los fármacos , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/fisiopatología , Evaluación Preclínica de Medicamentos , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Humanos , Canales Iónicos/metabolismo , Microdominios de Membrana , Actividad Motora/efectos de los fármacos , Factores de Crecimiento Nervioso/biosíntesis , Proteínas del Tejido Nervioso/fisiología , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Enfermedades Neurodegenerativas/fisiopatología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Ratas , Receptores sigma/fisiología , Degeneración Retiniana/tratamiento farmacológico , Degeneración Retiniana/fisiopatología , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Trastornos Relacionados con Sustancias/fisiopatología , Respuesta de Proteína Desplegada , Receptor Sigma-1RESUMEN
BACKGROUND: During the transformation to dedifferentiated thyroid cancer (TC) types, the ability of papillary thyroid carcinomas (PTCs) to concentrate radioactive iodine might be lost, raising difficulty for the current therapy. circRNAs were proved to be implicated in the progression of various cancers. In this study, we aimed to investigate the functional role and mechanism of hsa_circ_0023990 in dedifferentiated TC. METHODS: The expression pattern of genes were detected using quantitative PCR or western blot assays. Cell proliferation was determined by CCK8, colony formation, EdU, and cell-cycle assays. Glycolysis was assessed using glucose uptake and lactate production assays. Luciferase reporter assay was performed to examine the interactions between miR-485-5p and hsa_circ_0023990 or FOXM1. Xenograft assay was allowed for observation of tumor growth in vivo. RESULTS: Hsa_circ_0023990 and FOXM1 were upregulated in dedifferentiated TC tissues and cell lines. The higher level of hsa_circ_0023900 could stimulate the proliferation and glycolysis of dedifferentiated TC cells via positively regulating FOXM1. Mechanistically, miR-485-5p was demonstrated to interact with hsa_circ_0023990 and FOXM1 and involved in the regulation of has_circ_0023990 and FOXM1 in TC biological processes. CONCLUSION: Our results discovered the functional network of hsa_circ_0023990 in dedifferentiated TC development by facilitating cell proliferation and glycolysis via miR-485-5p/FOXM1 axis, implying that hsa_circ_0023990 might be a potential therapeutic target for the dedifferentiated TC treatment.
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Proteína Forkhead Box M1/genética , MicroARNs/genética , ARN Circular/fisiología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Anciano de 80 o más Años , Desdiferenciación Celular/genética , Proliferación Celular/genética , Células Cultivadas , Femenino , Regulación Neoplásica de la Expresión Génica , Glucólisis/genética , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genéticaRESUMEN
This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.
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Criptocromos/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Hipotálamo/efectos de los fármacos , Privación de Sueño/tratamiento farmacológico , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Criptocromos/genética , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Medicamentos Herbarios Chinos/farmacología , Glucosa/metabolismo , Hipotálamo/metabolismo , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Regulación hacia ArribaRESUMEN
With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.
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Medios de Contraste/farmacología , Proteína HMGB1/metabolismo , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Transporte Activo de Núcleo Celular/efectos de los fármacos , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Quimiocina CCL2/metabolismo , Diatrizoato de Meglumina/farmacología , Células Epiteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Ácido Glicirrínico/farmacología , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Interleucina-6/metabolismo , Túbulos Renales/metabolismo , Necrosis/inducido químicamente , Necrosis/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 2/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
We aimed to investigate whether the prognostic nutritional index (PNI), a combined nutritional-inflammatory score based on serum albumin levels and lymphocyte count, was associated with mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). From September 2011 to November 2014, 309 consecutive patients with STEMI undergoing pPCI were prospectively enrolled. Patients with a combined score of albumin (g/L) + 5 × total lymphocyte count × 109/L ≥ 45 or <45 were assigned a PNI score of 0 or 1, respectively. Of the 309 STEMI patients, 24 (7.74%) died in the hospital, and 15 (4.83%) died during long-term follow-up (median follow-up time, 19.5 [3-36] months). Compared to patients with a PNI of 0, patients with a PNI of 1 had significantly higher in-hospital (14.2% vs. 3.7%; P < 0.001) and long-term follow-up (21.7% vs. 6.9%, P < 0.001) mortality rates. PNI (1/0, HR, 2.414; 95% CI, 1.016 to 5.736; P = 0.046) was a significant independent predictor of mortality in patients with STEMI undergoing pPCI. Moreover, cumulative survival was significantly lower for patients with a PNI of 1 compared to patients with a PNI of 0 (78.3% vs. 93.1%, log-rank P < 0.001). PNI appears useful for the risk stratification of STEMI patients undergoing pPCI.
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Estado Nutricional , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/mortalidad , Anciano , Biomarcadores , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Intervención Coronaria Percutánea/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Infarto del Miocardio con Elevación del ST/cirugía , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The aim of the present study was to investigate the predictive value of the plasma matrix metalloproteinase-9 (MMP-9) level at admission for in-hospital mortality in patients who received emergency percutaneous coronary intervention (PCI) following AMI. A single blood sample was collected at admission from 155 consecutive AMI patients who underwent emergent PCI. The plasma levels of MMP-9 value (528.9±191.6 ng/ml) were significantly higher in the patients who died (n=24) than in the survivors (385.4±236.0 ng/ml) during 14 days of hospitalization (P=0.005). The age, left ventricle wall motion score index (WMIS), Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) levels and GENSINI score at admission were significantly different between the patients who died and those who survived (P<0.001, P=0.004, P<0.001 and P<0.001, respectively). Cut-off concentrations for prediction of death was identified from receiver operator characteristic (ROC) curves. Using the cut-off value (MMP-9 level 398.2 ng/ml) to stratify the patients into two groups, the group with higher MMP-9 levels had a greater rate of in-hospital mortality than the lower level group (P<0.001). With the exception of the GRACE score, among all biomarkers measured, in stepwise multiple logistic regressions, only the MMP-9 level predicted the risk of in-hospital death after adjustment for all other risk factors (odds ratio 5.02, 95% CI 1.44 to 17.55). In conclusion, a higher MMP-9 level is an independent predictor of in-hospital death in AMI patients who received emergency PCI.
RESUMEN
In this study, we examined the long noncoding RNA (lncRNA) expression pattern in Uyghur patients (a minority of China) with acute myocardial infarction (AMI) on a genome-wide scale. Total RNAs were extracted from the peripheral blood of 55 Uyghur AMI patients and 55 healthy volunteers. The expression levels of genome-wide scale lncRNAs and mRNAs were determined by microarray in 10 samples (5 AMI and 5 controls). qRT-PCR was used to validate lncRNA expression levels in 100 samples (50 AMI and 50 controls). Data analyses were performed using R and Bioconductor. A total of 3624 up- and 1637 down-regulated lncRNAs were identified to be significantly and differentially expressed between these two groups. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was regulation of biological processes, and the most significantly related pathway was apoptosis and its corresponding p53. The microarray identified ENST00000416860.2, ENST00000421157.1 and TCONS_00025701 lncRNAs were confirmed by qRT-PCR. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in the peripheral blood of AMI patients when compared with healthy controls within the Uyghur population. These newly identified lncRNAs may have a potential role in the development of AMI.
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Estudio de Asociación del Genoma Completo , Infarto del Miocardio/genética , ARN Largo no Codificante/genética , Transcriptoma , Adulto , Anciano , Estudios de Casos y Controles , China , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , ARN Mensajero/genéticaRESUMEN
Impaired myocardial reperfusion, defined angiographically by myocardial blush grade (MBG) 0 or 1, is associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the impact of admission mean platelet volume (MPV) on the myocardial reperfusion and 30-day all-cause mortality in patients with STEMI with successful epicardial reperfusion after primary percutaneous coronary intervention (PCI). A total of 453 patients with STEMI who underwent primary PCI within 12 h of symptoms onset and achieved thrombolysis in myocardial infarction (TIMI) 3 flow at infarct-related artery after PCI were enrolled and divided into two groups based on postinterventional MBG: those with MBG 2/3 and those with MBG 0/1. Admission MPV was measured before coronary angiography. The primary endpoint was all-cause mortality at 30 days. MPV was significantly higher in patients with MBG 0/1 than in patients with MBG 2/3 (10.38 ± 0.98 vs. 9.59 ± 0.73, P < 0.001). The cumulative 30-day all-cause mortality rate was significantly higher in the groups with high MPV and MBG 0/1 (6.8 vs. 1.5%, P = 0.005, 7.6 vs. 1.9%, P = 0.006, respectively). Multivariate logistic regression analysis demonstrated MPV was independently associated with postinterventional impaired myocardial reperfusion (odds ratio 2.684, 95% confidence interval 2.010-3.585, P < 0.001) and 30-day all-cause mortality (hazard ratio 1.763, 95% confidence interval 1.009-3.079, P = 0.046). Increased MPV on admission is an independent predictor of impaired myocardial reperfusion and short-term mortality in patients with STEMI with successful epicardial reperfusion after primary PCI. Admission MPV may be additive to conventional risk factors in patients with STEMI undergoing PCI.
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Volúmen Plaquetario Medio/métodos , Infarto del Miocardio/sangre , Reperfusión Miocárdica/métodos , Intervención Coronaria Percutánea/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Type A acute aortic dissection is a life-threatening vascular emergency because of its high morbidity and mortality. Platelet is a pivotal ingredient involved in the development of acute aortic dissection. In this study, we aimed to investigate whether mean platelet volume (MPV)/platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection. In this single-center and prospective cohort study, 106 consecutive patients with Stanford type A acute aortic dissection admitted to the hospital within 12âh after onset were recruited. The best cut-off value of MPV/platelet count ratio predicting all-cause mortality was determined by the receiver operator characteristic analysis. Patients were divided into high (H-MPV/platelet count) and low (L-MPV/platelet count) groups based on the cut-off value of 7.49 (10âfl/10/l). Patients were followed up for 3.5 years. Of the 106 acute aortic dissection patients, 71 (67.0%) died during the study period, with a median follow-up duration of 570 days. Compared to the L-MPV/platelet count group, patients with H-MPV/platelet count had a higher risk of in-hospital complications including hypotension, hypoxemia, myocardial ischemia/infarction, conscious disturbance, pericardial tamponade, paraplegia, and poor survival (all Pâ<â0.05). In multivariable Cox regression models adjusted for potential confounders, MPV/platelet count ratio was positively associated with the hazard of all-cause mortality, irrespective of interventions either with medication only or urgent surgery, and the hazard ratios were 2.81 (95% confidence interval 1.28-4.48) for the H-MPV/platelet count group when taking L-MPV/platelet count group as the reference (Pâ=â0.005). The MPV/platelet count ratio was a strong independent predictor for in-hospital complications and long-term mortality in patients with type A acute aortic dissection.