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ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 (ACAP3) level has been confirmed to be downregulated in papillary thyroid carcinoma (PTC). Histone deacetylase inhibitors (HDACIs) have therapeutic effects on PTC. Accordingly, this study probed into the potential relation of histone deacetylase 2 (HDAC2) and ACAP3 in PTC. Expressions of ACAP3 and HDAC2 in PTC were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between HDAC2 and ACAP3 was predicted by Pearson analysis. Cell functional assays (cell counting kit-8, transwell, wound healing and flow cytometry assays) and rescue assay were carried out to determine the effects of HDAC2/ACAP3 axis on biological behaviors of PTC cells. Expressions of apoptosis-, epithelial-mesenchymal transition-, Protein Kinase B (AKT)-, and P53-related proteins were measured by Western blot. ACAP3 level was downregulated in PTC tissues and cells. ACAP3 overexpression (oe-ACAP3) suppressed viability, proliferation, migration and invasion of PTC cells, facilitated apoptosis, downregulated the expressions of Protein Kinase B (Bcl-2) and N-cadherin, upregulated the expressions of Bcl-2 associated protein X (Bax) and E-cadherin, diminished the p-AKT/AKT ratio and elevated the p-p53/p53 ratio; however, ACAP3 silencing or HDAC2 overexpression (oe-HDAC2) did the opposite. HDAC2 negatively correlated with ACAP3. The tumor-suppressing effect of oe-ACAP3 in PTC was reversed by oe-HDAC2. Collectively, ACAP3 negatively regulated by HDAC2 suppresses the proliferation and metastasis while facilitating apoptosis of PTC cells.
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Objective: To analyze the trends in disease burden of diabetes-related chronic kidney disease (CKD) by year, age, gender and types of diabetes in China from 1990 to 2019. Methods: Data on prevalence, deaths and disability-adjusted life years (DALYs) for diabetes-related CKD were extracted from the Global Burden of Disease (GBD) 2019 study. Analyses were performed by year, age, gender and types of diabetes. Results: In China, the numbers of deaths and DALYs of diabetes-related CKD continuously increased but the age-standardized rates (per 100,000 population) decreased over 30 years, in which the numbers of deaths and DALYs attributable to type 1 diabetes mellitus (T1DM)-related CKD barely changed and the age-standardized rates decreased over the years; and the number of deaths and DALYs attributable to type 2 diabetes mellitus (T2DM)-related CKD continuously increased, but the age-standardized rates also decreased. In 2019, 76.03 (58.24-95.61) thousand deaths and 2.13 (1.65-2.67) million DALYs were attributable to diabetes-related CKD, of which, T2DM accounted for 83.32% and 77.0% respectively, and T1DM accounted for the rest. Increasing gender disparity was seen, with males being more heavily impacted. The burden of diabetes-related CKD varied among different age groups, with the numbers of deaths and DALYs attributable to T1DM-related CKD peaking between 45 and 54 years of age and T2DM-related CKD peaking between 75 and 79 years of age; and the crude rates of deaths and DALYs attributable to T1DM-related CKD peaking between 70 and 79 years of age and 40 to 54 years of age, respectively, and T2DM-related CKD peaking over 90 years of age. Among neighboring and G20 countries, the burden of diabetes-related CKD in China was relatively controlled reflected by the ranking of adjusted death and DALYs rates. Conclusions: The burden of diabetes-related CKD in China worsens and shows gender disparities and different age distribution. Greater efforts are needed to improve the health outcomes of these patients, especially among males.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Adulto , Anciano de 80 o más Años , China/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Lactante , Masculino , Años de Vida Ajustados por Calidad de Vida , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiologíaRESUMEN
Background: The impact of hypoxia on ferroptosis is important in cancer proliferation, but no predictive model combining hypoxia and ferroptosis for adrenocortical carcinoma (ACC) has been reported. The purpose of this study was to construct a predictive model based on hypoxia- and ferroptosis-related gene expression in ACC. Methods: We assessed hypoxia- and ferroptosis-related gene expression using data from 79 patients with ACC in The Cancer Genome Atlas (TCGA). Then, a predictive model was constructed to stratify patient survival using least absolute contraction and selection operation regression. Gene expression profiles of patients with ACC in the Gene Expression Omnibus (GEO) database were used to verify the predictive model. Results: Based on hypoxia-related gene expression, 79 patients with ACC in the TCGA database were divided into three molecular subtypes (C1, C2, and C3) with different clinical outcomes. Patients with the C3 subtype had the shortest survival. Ferroptosis-related genes exhibited distinct expression patterns in the three subtypes. A predictive model combining hypoxia- and ferroptosis-related gene expression was constructed. A nomogram was constructed using age, sex, tumor stage, and the predictive gene model. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the gene signature was mainly related to the cell cycle and organelle fission. Conclusion: This hypoxia-and ferroptosis-related gene signature displayed excellent predictive performance for ACC and could serve as an emerging source of novel therapeutic targets in ACC.
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Background: Low bone mineral density (LBMD), including osteoporosis and low bone mass, has becoming a serious public health concern. We aimed to estimate the disease burden of LBMD and its related fractures in 204 countries and territories over the past 30 years. Methods: We collected detailed information and performed a secondary analysis for LBMD and its related fractures from the Global Burden of Disease Study 2019. Numbers and age-standardized rates related to LBMD of disability-adjusted life-years (DALYs) and deaths in 204 countries and territories were compared by age, gender, socio-demographic index (SDI), and location. Results: Global deaths and DALYs number attributable to LBMD increased from 207 367 and 8 588 936 in 1990 to 437 884 and 16 647 466 in 2019, with a raise of 111.16% and 93.82%, respectively. DALYs and deaths number of LBMD-related fractures increased 121.07% and 148.65% from 4 436 789 and 121248 in 1990 to 9 808 464 and 301 482 in 2019. In 2019, the five countries with the highest disease burden of DALYs number in LBMD-related fractures were India (2 510 288), China (1 839 375), United States of America (819 445), Japan (323 094), and Germany (297 944), accounting for 25.59%, 18.75%, 8.35%, 3.29%, and 3.04%. There was a quadratic correlation between socio-demographic index (SDI) and burden of LBMD-related fractures: DALYs rate was 179.985-420.435SDI+417.936SDI2(R2 = 0.188, p<0.001); Deaths rate was 7.879-13.416SDI+8.839 SDI2(R2 = 0.101, p<0.001). Conclusions: The global burden of DALYs and deaths associated with LBMD and its related fractures has increased significantly since 1990. There were differences in disease burden between regions and countries. These estimations could be useful in priority setting, policy-making, and resource allocation in osteoporosis prevention and treatment.
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Carga Global de Enfermedades , Osteoporosis , China/epidemiología , Salud Global , Humanos , Osteoporosis/epidemiología , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Dietary risks have raised attention worldwide during recent decades. The present burden-of-disease study aimed to evaluate the global dietary risks for non-communicable diseases (NCDs) from 1990 to 2019 and quantify their impact on mortality and disability-adjusted life-years (DALYs). Data from the 2019 Global Burden of Disease Study on deaths and DALYs from NCDs attributable to worldwide dietary risks were obtained and underwent deep analysis by year, age, gender, location, leading risks and leading causes, and their associations were examined. The socio-demographic index (SDI) was used as an indicator of national socio-economic status, as well as the relationships between age-standardised rates of deaths or DALYs and socio-economic status. RESULTS: In 2019, 7.9 million deaths and 187.7 million DALYs were attributable to dietary risk factors. High intake of sodium and low intake of whole grains and fruits were leading dietary risks for deaths and DALYs worldwide. However, both indices showed a decreasing trend by year, an increase by age and a higher disease burden in males. The main distribution of dietary-related NCDs was located in highly populated countries. A negative association between the SDI and disease burden and a positive association between the SDI and male preponderance were found. CONCLUSIONS: Dietary risk factors for NCDs increased significantly and varied across regions during 1990-2019. Therefore, greater efforts are needed to raise public awareness of interventions and improve dietary practices aiming to reduce the disease burden caused by suboptimal dietary intake, especially in developing countries and among males.
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Enfermedades no Transmisibles , Costo de Enfermedad , Carga Global de Enfermedades , Salud Global , Humanos , Masculino , Enfermedades no Transmisibles/epidemiología , Años de Vida Ajustados por Calidad de Vida , Factores de RiesgoRESUMEN
Objective: Recently, Nonalcoholic Steatohepatitis (NASH) has become a major contributor to cirrhosis and liver cancer. Therefore, the Global Burden of Disease (GBD) 2017 was used to comprehensively analyze the global, regional, and national burden of cirrhosis and liver cancer due to NASH between 1990 and 2017. Methods: Data for cirrhosis and liver cancer due to NASH were extracted from the GBD study 2017. Socio-demographic Index (SDI) in 2017 was cited as indicators of socioeconomic status. ARIMA model was established to forecast the future health burden. Kruskal-Wallis test and Pearson linear correlation were adopted to evaluate the gender disparity and association with socioeconomic level. Results: From 1990-2017, the global disability-adjusted life years (DALYs) numbers of liver cancer due to NASH increased from 0.71 million to 1.46 million. The age-standardized DALYs rates of liver cancer due to NASH were negatively associated with SDI levels (r=0.-409, p<0.001). Geographically, Australasia experienced the largest increase in the burden of liver cancer due to NASH, with the age-standardized DALYs rate increasing by 143.54%. The global prevalence number of liver cancer due to NASH peaked at 60-64 years in males and at 65-69 years in females. Globally, the burden was heavier in males compared with females. Male-female-ratio of age-standardized DALYs rates in liver cancer due to NASH were positively related to SDI (r=0.303, P=0.011). Conclusion: The global burden of NASH-associated liver cancer has increased significantly since 1990, with age, gender and geographic disparity. Public awareness of liver diseases due to NASH should be emphasized.
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BACKGROUND: Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery. CASE PRESENTATION: A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes. CONCLUSIONS: She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.
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Diabetes Insípida Nefrogénica/congénito , Diabetes Insípida Neurogénica/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Adenoma/complicaciones , Adenoma/cirugía , Adulto , China , Diabetes Insípida Nefrogénica/complicaciones , Diabetes Insípida Nefrogénica/diagnóstico , Diabetes Insípida Nefrogénica/genética , Diabetes Insípida Neurogénica/diagnóstico , Femenino , Humanos , Mutación Missense , Apoplejia Hipofisaria/diagnóstico , Apoplejia Hipofisaria/etiología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Receptores de Vasopresinas/genética , Adulto JovenRESUMEN
BACKGROUND: Many studies have shown an elevated level of cholesterol in colon tumors as compared to normal tissue. Obesity and high low-density lipoprotein cholesterol (LDL-C) are known risk factors for colon cancer. However, the role of LDL-C in colon cancer patients with normal body mass index (BMI) remains elusive. METHODS: Levels of serum cholesterol and oxysterols were quantified by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) from 129 individuals with normal BMI, including 32 with solitary polyp, 36 with multiple polyps, and 31 with adenocarcinoma as well as 32 healthy controls. In vitro, colon cancer cells were treated with LDL-C and assayed for chemokines via RNA-Seq and mitochondrial morphology via transmission electron microscopy and immunofluorescence. Additionally, correlation analysis was performed between LDL-C-induced chemokines and the overall survival of colon cancer patients from the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA) database. RESULTS: The serum cholesterol level was significantly higher in colon adenocarcinoma patients with normal BMI than that in healthy controls (P<0.001). LDL-C potentiated colon cancer cell invasion and resistance to glucose-deprivation in vitro via chemokine-mediated signaling, mainly upregulation of CC chemokine ligand (CCL) 5 and downregulation of CCL 11. By analyzing the RNA expression data of colorectal cancer from TCGA, GTEx, and HPA, we demonstrated that the CCL5 level in colorectal adenocarcinoma tissues was significantly increased relative to adjacent normal tissues (P=0.01) while the CCL11 level was decreased (P=0.01). Both increased CCL5 and decreased CCL11 showed a negative correlation with the 5-year overall survival in tumor node metastasis (TNM) stage II colon cancer patients (P=0.0032, 0.026 for CCL5 and CCL11, respectively). CONCLUSIONS: Our study supports the idea that LDL-C regulates the expression of CCL5 and CCL11 chemokines, which may have predictive values for survival in colon cancer patients with normal BMI, especially for patients in TNM stage II.
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A high-fat diet (HFD) is defined as a diet that contains lipids that account for more than 30% of the total energy intake, and current research has documented cases with intakes as high as 45% and 60%. There is a view that patients who have a tendency to consume a HFD are more susceptible to various kinds of diseases, including osteoporosis, metabolic syndrome, coronary heart disease, and cancer. Thus, hypotheses have been proposed that a HFD may serve as a significant risk factor for bone loss and osteoporosis. A plethora of studies has suggested a relationship between a HFD and bone health. Moreover, high fat has a vital effect on the bone structure and bone health, and intestinal flora imbalances and intestine barrier deterioration, inflammation, oxidative stress, adipokine changes, and bone marrow fat tissue (BMFT) accumulation are thought to be potential mechanisms. Most research has demonstrated that a HFD diminishes bone mineral density and bone microstructure. Some studies, however, showed that a HFD contributes to achieving peak bone mass, which is associated with weight gain. As diet is modifiable, lifestyle changes and medication can help bone improvement, as well as alleviating bone loss associated with a HFD. This review aims to give a comprehensive understanding of the relationship between a HFD and bone health, which might provide strategies to improve bone health by varying daily dietary components and building a healthy lifestyle. We also hope that further treatments for diet-related bone loss can be put forward.
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Huesos/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Osteoporosis/inducido químicamente , Animales , Densidad Ósea , Huesos/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , HumanosRESUMEN
INTRODUCTION: Diabetes insipidus can be a common cause of polyuria and hydronephrosis in the kidneys. However, there is few reported case of urinary obstruction induced nephrogenic diabetes insipidus. PATIENT CONCERNS: A 60-year-old Chinese man came to our hospital with the complaints of polydipsia and polyuria for 1 month. His examination showed chronic kidney disease stage III with eGFR of 48.274âml/min, and the plasma osmolality was 338.00âmOsm/(kg·H2O) with a urinary osmolality of 163.00âmOsm/(kg·H2O). Moreover, imagological examination of the urinary system showed benign prostatic hyperplasia and hydronephrosis. DIAGNOSIS: He was considered with benign prostatic hyperplasia induced ureter hydronephrosis and nephrogenic diabetes insipidus. INTERVENTIONS: He got the transurethral resection of the prostate to alleviate urinary retention. OUTCOMES: After that, the urine output gradually decreased, and the administered hydrochlorothiazide was stopped due to the improved renal function. CONCLUSION: Our study presents a case of nephrogenic diabetes insipidus caused by urinary obstruction. Differential diagnoses for diabetes insipidus as well as the relationship between nephrogenic diabetes insipidus and urinary obstruction are also considered in this study.
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Diabetes Insípida Nefrogénica/etiología , Hiperplasia Prostática/complicaciones , Obstrucción Ureteral/complicaciones , Fármacos Antidiuréticos/uso terapéutico , Desamino Arginina Vasopresina/uso terapéutico , Diabetes Insípida Nefrogénica/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Poliuria/tratamiento farmacológico , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata , Obstrucción Ureteral/etiologíaRESUMEN
Diabetes mellitus is a leading cause of mortality and reduced life expectancy. We aim to estimate the burden of diabetes by type, year, regions, and socioeconomic status in 195 countries and territories over the past 28 years, which provide information to achieve the goal of World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases in 2025. Data were obtained from the Global Burden of Disease Study 2017. Overall, the global burden of diabetes had increased significantly since 1990. Both the trend and magnitude of diabetes related diseases burden varied substantially across regions and countries. In 2017, global incidence, prevalence, death, and disability-adjusted life-years (DALYs) associated with diabetes were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, with a projection to 26.6 million, 570.9 million, 1.59 million, and 79.3 million in 2025, respectively. The trend of global type 2 diabetes burden was similar to that of total diabetes (including type 1 diabetes and type 2 diabetes), while global age-standardized rate of mortality and DALYs for type 1 diabetes declined. Globally, metabolic risks (high BMI) and behavioral factors (inappropriate diet, smoking, and low physical activity) contributed the most attributable death and DALYs of diabetes. These estimations could be useful in policy-making, priority setting, and resource allocation in diabetes prevention and treatment.
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Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Carga Global de Enfermedades/tendencias , Salud Global , Esperanza de Vida , Mortalidad/tendencias , Medición de Riesgo/métodos , Diabetes Mellitus Tipo 1/mortalidad , Diabetes Mellitus Tipo 2/mortalidad , Humanos , Incidencia , Agencias Internacionales , Pronóstico , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Hyperglycemia is a major public health concern. An understanding of the latest trends of the global burden of noncommunicable diseases (NCDs) by high fasting plasma glucose (HFPG) is critical for determining research priorities and planning health policy. METHODS: This is a comparative burden-of-disease study. We obtained global, regional, and national data on deaths and disability-adjusted life years (DALYs) of NCDs attributable to HFPG from the Global Burden of Disease Study 2017, performed a secondary analysis of deaths and DALYs by time, age, gender, location, and specific causes, and analyzed their associations. RESULTS: In 2017, 6.39 million deaths and 166.36 million DALYs from NCDs were attributable to HFPG, accounting for 15.6% and 10.7% of all deaths and DALYs, respectively. The burden's rate decreased with time, increased with age and was significantly higher in males. A negative association was found between the sociodemographic index (SDI) and disease burden, and a positive association was found between SDI and male superiority by gender difference and gender ratio. CONCLUSIONS: The burden of NCDs attributable to HFPG has increased significantly since 1990 and varied widely across regions. Greater efforts are needed to prevent and control hyperglycemia, especially in less developed countries and among males.
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Glucemia/metabolismo , Costo de Enfermedad , Ayuno/sangre , Salud Global/estadística & datos numéricos , Enfermedades no Transmisibles/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Geografía , Humanos , Masculino , Persona de Mediana Edad , Enfermedades no Transmisibles/clasificación , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies. Patients with IAS usually complain of hypoglycemia without any previous insulin received. Glucocorticoids and immunosuppressants are used to treat IAS. CASE PRESENTATION: We report four patients with diabetes who were diagnosed with non-classical IAS and describe the treatment of these patients. Moreover, the differential diagnosis with hyperinsulinism is discussed. CONCLUSION: High levels of insulin autoantibodies, as well as hyperinsulinemic hypoglycemia, are found in patients with diabetes mellitus and prior exogenous insulin exposure. This situation that we classified as non-classical IAS should be attached importance to.
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Enfermedades Autoinmunes/inducido químicamente , Insulina/administración & dosificación , Insulina/inmunología , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hiperglucemia/sangre , Hiperglucemia/tratamiento farmacológico , Inyecciones , Anticuerpos Insulínicos/sangre , Masculino , Persona de Mediana Edad , SíndromeRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.
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Ácidos y Sales Biliares/metabolismo , Disbiosis/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Ensayos Clínicos como Asunto , Microbioma Gastrointestinal , Glucosa/metabolismo , Humanos , Metabolismo de los Lípidos , Ratones , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/terapia , Proteínas de Unión al ARN/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Factores de Riesgo , Transducción de SeñalRESUMEN
Insulin resistance (IR) is a fundamental pathogenic factor shared by a myriad of metabolic disorders, including obesity and type 2 diabetes. The mechanism of IR is usually accompanied by mitochondrial dysfunction. Irisin has been proposed to act as a hormone in the regulation of energy homeostasis and metabolism. However, the effects of irisin on IR and mitochondrial function have not yet been fully investigated. Here, our research shows that irisin increases glucose uptake in C2C12 myoblast cells via the p38-mitogen-activated protein kinase (MAPK)-PGC-1α pathway. Irisin can also enhance mitochondrial function and mitochondrial respiration. Moreover, irisin stimulates autophagy via PGC-1α. Collectively, these data provide basic evidence to support the therapeutic potential of irisin for IR, which may rely on p38-MAPK-PGC-1α pathway activation and enhance mitochondrial function.
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Fibronectinas/farmacología , Resistencia a la Insulina , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mioblastos Esqueléticos/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Línea Celular , Fibronectinas/metabolismo , Humanos , Mitocondrias Musculares/metabolismo , Mioblastos Esqueléticos/citologíaRESUMEN
BACKGROUND: Cancer stem cells (CSCs) play a critical role in tumor development and progression and are involved in cancer metastasis. The role of reactive oxygen species (ROS) in CSCs and cancer metastasis remains controversial. The aim of the present study was to investigate the correlation between ROS level of CSCs and cancer metastasis and to explore the possible underlying molecular mechanisms. METHODS: Four different cell lines were used to isolate tumor spheres and to analyze intrinsic properties of tumor sphere cells including proliferation, self-renewal potential, differentiation, drug-resistance and cancer metastasis in vitro and in vivo. ROS assays were used to detect the intracellular ROS level of tumor spheres cells. Gene expression analysis and western blot were used to investigate the underlying mechanisms of ROS in regulating cancer metastasis. RESULTS: Tumor spheres possessed the characteristic features of CSCs, and ROS-high tumor spheres (RH-TS) displayed elevated mitochondrial ROS level exclusively drove metastasis formation. The gene expression analysis showed elevated fatty acid ß-oxidation, downregulation of epithelial marker upregulation of mesenchymal markers, and the activation of MAP kinase cascades. Furthermore, 14 up-regulated genes in RH-TS cells were associated with reduced overall survival of different cancer patients. CONCLUSIONS: Our findings demonstrate that CSCs characterized by elevated mitochondrial ROS level potentiate cancer metastasis. Mechanistically, elevated mitochondrial ROS via fatty acid ß-oxidation, activates the MAPK cascades, resulting in the epithelial-mesenchymal transition (EMT) process of RH-TS cells, thereby potentiating caner invasion and metastasis. Therefore, targeting mitochondrial ROS might provide a promising approach to prevent and alleviate cancer metastasis induced by RH-TS cells.
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Transición Epitelial-Mesenquimal/fisiología , Mitocondrias/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Células Madre Neoplásicas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Femenino , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Células HCT116 , Células HT29 , Humanos , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Oxidación-Reducción , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Objective To investigate the expression of apoptosis-related factors in diabetic nephropathy model rats after the intervention of dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. Methods ZDF(fa/fa) and ZDF(fa/+) rats were randomly divided into diabetes mellitus group and sitagliptin treatment group, and ZDF control mice (fa/+) were used as the control group. Non-fasting blood glucose levels were measured with glucose oxidase kit. Urine albumin level was detected by ELISA, and blood biochemical indexes were detected by automatic biochemical analyzer. The mRNA levels of tumor necrosis factor receptor 1(TNFR1), Fas, and caspase-3 in the renal tissue were examined by real-time fluorescence quantitative PCR, and the protein levels of DPP-4, GLP-1, TNFR1, caspase-3, and caspase-8 were detected by Western blot analysis. Results The levels of blood glucose, urinary microalbumin, blood urea nitrogen, serum creatinine increased in the diabetic group, and the levels of related indicators significantly decreased after treatment with sitagliptin. The mRNA levels of TNFR1 and caspase-3 in the diabetic rats went up and then down after the treatment with sitagliptin. The levels of DPP-4, TNFR1, caspase-3 and caspase-8 in the diabetic rats increased, while the level of GLP-1 decreased; after the treatment with sitagliptin, the corresponding protein content showed opposite changes. Conclusion Sitagliptin can inhibit inflammation and apoptosis in rats with diabetic nephropathy.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Animales , Apoptosis , Inflamación , Ratones , Ratas , Fosfato de SitagliptinaRESUMEN
RATIONALE: Hyperpigmentation is a common skin disease. However, there are few reported cases of Grave's disease with diffuse hyperpigmentation. We hereby described a rare case with diffuse hyperpigmentation induced by Grave's disease. PATIENT CONCERNS: A 42-year-old Chinese woman with accumulated general pigmentation of skin was admitted to our hospital in October 2017. On examination, hyperpigmentation was observed throughout the whole body, especially on the extremities and the face. DIAGNOSES: The patient has elevated levels of serum free thyroxine (FT4), free triiodothyronine (FT3), reduced levels of thyroid-stimulating hormone (TSH) and positive anti-TSH receptor antibody (TRAb). She presented with grade I goiter and a diffusely increased thyroid uptake to 18.5% in thyroid scan. Histopathological examination demonstrated melanin pigmentation in the pigmented skin area. The patient was diagnosed with hyperpigmentation induced by Grave's disease. INTERVENTIONS: The patient was treated with oral methimazole (15âmg/day) for thyroid dysfunction and beta blocker for symptom control. OUTCOMES: After a period of treatment with methimazole and beta blocker, symptoms of hyperthyroidism ameliorated and hyperpigmentation abated. LESSONS: Our studies proposed that in this case the diffuse hyperpigmentation in Grave's disease was caused by elevated adrenocorticotropic hormone (ACTH) as well as anti- TSH receptor stimulating antibody instead of enhanced capillary fragility. Other potential mechanisms for skin pigmentation in hyperthyroidism still need further exploration.
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Enfermedad de Graves/complicaciones , Enfermedad de Graves/diagnóstico , Hiperpigmentación/diagnóstico , Hiperpigmentación/etiología , Adulto , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/patología , Humanos , Hiperpigmentación/tratamiento farmacológico , Hiperpigmentación/patologíaRESUMEN
Colorectal cancer (CRC) is one of the most malignant cancers, and it tends to migrate to the liver and has a high mortality rate. Several mechanisms behind the metastasis of CRC have been identified, including hyperlipidemia. For example, hyperlipidemia can lead to enhanced stemness and neutrophil infiltration, which increases CRC metastasis. There are three primary aspects to the relationship between hyperlipidemia and CRC metastasis: hyperlipidemia (1) promotes the initial metastatic properties of CRC, (2) stimulates CRC cells to leave the vasculature, and (3) facilitates the development of CRC metastasis. In this study, we provide a comprehensive overview of the role that hyperlipidemia played in CRC metastasis to help reduce the mortality associated with CRC metastasis from the standpoint of metabolic. We also review cancer metastasis.
RESUMEN
Carotid atherosclerosis (CA) and carotid plaque (CP) are highly correlated with cardiovascular disease. We aimed to determine the prevalence of CA and CP and their relationship with 10-year risks of stroke and coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM).We studied 1584 T2DM patients aged 20 years and older. CA and CP were detected using ultrasonography. Ten-year stroke and CHD risk were determined using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine.The prevalence of CA and CP increased gradually with age. Men had a higher prevalence of CA than women (CA: 58.18% vs 51.54%, Pâ<â.01). The 10-year CHD risk (27.9% vs 15.4%, Pâ<â.001) and stroke risk (15.2% vs 5.70%, Pâ<â.001) were higher in patients with CA than that of those without CA. Compared with patients without CA, the odds ratios (ORs) of CHD in CA and CP group were 4.47 and 10.78 for men, and 4.19 and 5.20 for women, respectively; in the case of stroke, the OR in CA and CP group were 8.83 and 12.07 for men, and 4.35 and 4.90 for women, respectively (Pâ<â.001 for all). Multivariate binary logistic regression analysis showed that CA was an independent risk factor for CHD [ORâ=â2.66, 95% confidence interval (95% CI), 2.05-3.46, Pâ<â.001] and stroke (ORâ=â3.11, 95% CI, 2.38-4.07, Pâ<â.001).CA and CP were prevalent in patients with T2DM and positively correlated with 10-year CHD and stroke risk. CA was an independent risk factor for 10-year CHD risk.