RESUMEN
BACKGROUND: Triglyceride and glucose (TyG) index, a surrogate marker of insulin resistance, has been validated as a predictor of cardiovascular disease. However, effects of TyG-related indices combined with obesity markers on cardiovascular diseases remained unknown. We aimed to investigate the associations between TyG index and modified TyG indices with new-onset cardiovascular disease and the time-dependent predictive capacity using a national representative cohort. METHODS: This study is a retrospective observational cohort study using data from China Health and Retirement Longitudinal Study (CHARLS) of 7 115 participants. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The modified TyG indices were developed combining TyG with body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). We used adjusted Cox proportional hazards regression to analyze the association and predictive capacity based on hazard ratio (HR) and Harrell's C-index. RESULTS: Over a 7-year follow-up period, 2136 participants developed cardiovascular disease, including 1633 cases of coronary heart disease and 719 cases of stroke. Compared with the lowest tertile group, the adjusted HR (95% CI) for new-onset cardiovascular disease in the highest tertile for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.215 (1.088-1.356), 1.073 (0.967-1.191), 1.078 (0.970-1.198), and 1.112 (1.002-1.235), respectively. The C-indices of TyG index for cardiovascular disease onset were higher than other modified TyG indices. Similar results were observed for coronary heart disease and stroke. CONCLUSION: TyG and TyG-WhtR were significantly associated with new-onset cardiovascular diseases, and TyG outperformed the modified TyG indices to identify individuals at risk of incident cardiovascular event.
Asunto(s)
Biomarcadores , Glucemia , Enfermedades Cardiovasculares , Triglicéridos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Biomarcadores/sangre , Glucemia/metabolismo , Glucemia/análisis , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Pueblos del Este de Asia , Factores de Riesgo de Enfermedad Cardiaca , Incidencia , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Triglicéridos/sangre , Circunferencia de la CinturaRESUMEN
BACKGROUND: Body image dissatisfaction, leading to a variety of negative emotions and adverse pregnancy or birth outcomes. Studies on body image interventions for pregnant and postpartum women have been reported, yielding mixed results. Existing evidence lacks a comprehensive review of the effectiveness of body image interventions for pregnant and postpartum women. OBJECTIVE: The aim of this study was to systematically review interventions which aimed at improving body image during pregnancy and postpartum in women of childbearing age, and further to explore their effectiveness. METHODS: A comprehensive literature search was conducted using electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SinoMed, CNKI, and Wanfang Database, to retrieve relevant studies. Body image was reported employing descriptive analysis, whereas the Cochrane Handbook tool was used to evaluate the quality and potential bias of each included study. RESULTS: Following established inclusion and exclusion criteria, 11 studies were identified from an initial 1,422 records for further analysis, involving 1290 participants. This systematic review grouped body image interventions into lifestyle interventions and psychological interventions based on their content. These interventions yielded more pronounced positive effects on improving body image in pregnant and postpartum women when compared to control groups. And, the statistical difference on psychological interventions is more significant on the whole. CONCLUSIONS: Our work offers a comprehensive overview of the effectiveness of body image interventions for pregnant and postpartum women. Psychological interventions are considered to be a suitable measure to improve body image for pregnant or postpartum women. Additional research and practical applications are recommended to enhance the mental health and well-being of perinatal women. TRIAL REGISTRATION: PROSPERO registry: CRD42024531531.
Asunto(s)
Imagen Corporal , Periodo Posparto , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Embarazo , Imagen Corporal/psicología , Periodo Posparto/psicología , Mujeres Embarazadas/psicología , AdultoRESUMEN
BACKGROUND AND AIMS: Visceral adiposity index (VAI), an indicator of visceral fat, is associated with metabolic health and arterial stiffness. However, studies correlating VAI and stroke are limited. This study aimed to explore the association between VAI and incident stroke in the Chinese population. METHODS AND RESULTS: We retrospectively analysed the data of 9127 individuals enrolled in the China Health and Retirement Longitudinal Study. The first survey of the study was conducted during 2011-2012 and the individuals were followed up until Survey 4 (2017-2018). Multivariable-adjusted Cox regression models were used to evaluate the association between VAI and stroke. The mean age of the study population was 59.3 ± 9.5 years and 4938 (54.1%) participants were women. During the median follow-up of 5.2 [1.0-7.0] years, 833 (9.1%) participants developed stroke, and the cumulative incidence of stroke increased with increasing quartiles of VAI (8.6%, 8.7%, 9.2%, and 10.0%). Compared to those in the first quartile of VAI, individuals in the fourth quartile had an increased risk of stroke (adjusted hazard ratio, 1.45; 95% CI, 1.15-1.75). The results were stable in several sensitivity analyses. CONCLUSION: Our findings suggest a positive association between VAI and incident stroke in the Chinese population.
Asunto(s)
Adiposidad , Accidente Cerebrovascular , Anciano , Índice de Masa Corporal , China/epidemiología , Femenino , Humanos , Grasa Intraabdominal , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Jubilación , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiologíaRESUMEN
Transforming growth factor beta (TGF-ß) plays key roles in regulating cellular proliferation and maintaining tissue homeostasis. TGF-ß exerts tumor-suppressive effects in the early stages of carcinogenesis, but it also plays tumor-promoting roles in established tumors. Additionally, it plays a critical role in cancer radiotherapy. TGF-ß expression or activation increases in irradiated tissues, and studies have shown that TGF-ß plays dual roles in cancer radiosensitivity and is involved in ionizing radiation-induced fibrosis in different tumor microenvironments (TMEs). Furthermore, TGF-ß promotes radioresistance by inducing the epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs), suppresses the immune system and facilitates cancer resistance. In particular, the links between TGF-ß and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) axis play a critical role in cancer therapeutic resistance. Growing evidence has shown that TGF-ß acts as a radiation protection agent, leading to heightened interest in using TGF-ß as a therapeutic target. The future of anti-TGF-ß signaling therapy for numerous diseases appears bright, and the outlook for the use of TGF-ß inhibitors in cancer radiotherapy as TME-targeting agents is promising.
Asunto(s)
Neoplasias/metabolismo , Neoplasias/radioterapia , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Resistencia a Antineoplásicos , Fibrosis , Humanos , Modelos Biológicos , Neoplasias/inmunología , Neoplasias/patologíaRESUMEN
BACKGROUND AND AIMS: We aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences. METHODS AND RESULTS: The China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05-1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98-1.29). In addition, the positive dose-response relationship between BMI increase and stroke was observed only in men. CONCLUSION: Among middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.
Asunto(s)
Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Obesidad/epidemiología , Accidente Cerebrovascular/epidemiología , Aumento de Peso , Factores de Edad , Anciano , China/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Accidente Cerebrovascular/diagnóstico , Factores de TiempoRESUMEN
BACKGROUND: An intro-abdominal hernia through the lesser omentum is a rare but severe condition that can cause intestinal obstruction and other life-threating complications. Until now, only a handful of cases have been reported worldwide. The diagnosis of lesser omental hernia remains challenging for emergency surgeons because of the unspecific symptoms. Therefore, there is a need for a better understanding of the characteristics of this condition. CASE PRESENTATION: In this report, we described the case of a 73-year-old female patient who was diagnosed with a lesser omental hernia caused by previous total colectomy. The patient underwent emergency surgery, and the intraoperative findings revealed a 200-cm segment of the small intestine was herniated through a defected lesser omentum (approximately 3 × 4 cm) from the lesser retrogastric curvature of the stomach. Besides, we summarize the specific abdominal computed tomography (CT) findings of lesser omental hernia by reviewing the literature. CONCLUSION: The lesser omental hernia is extremely rare but can cause serious complications. The cause of lesser omental hernia can be congenital or acquired. Careful examination of the small omentum before the closure of the abdomen is expected to reduce the occurrence of these abdominal surgery-associated complications. The specific features of abdominal CT in cases of lesser omental hernia, which are summarized in this article, can help other clinicians to obtain accurate diagnoses of lesser omentum hernia in the future.
Asunto(s)
Colectomía/efectos adversos , Hernia/etiología , Epiplón/patología , Anciano , Urgencias Médicas , Femenino , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Intestino Delgado/cirugía , Epiplón/cirugía , Enfermedades Peritoneales/patología , Tomografía Computarizada por Rayos XRESUMEN
DEHP is reported to cause precocious puberty of females in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of sexual precocity. Prepubertal female rats were treated with DEHP for 4 weeks. Key organs were analyzed in control conditions and after exposure to 0.2, 1, and 5â¯mg/kg/day DEHP in pubertal female rats. To determine the role of the IGF-1/PI3K/Akt/mTOR signaling pathway in DEHP-induced female precocious puberty, 36 rats were treated with 5â¯mg/kg/day DEHP to establish a model of female precocious puberty. And we investigated the expression of genes and proteins related to IGF-1 pathway in rat hypothalamus after treatment with inhibitors. In the present study, we observed that DEHP treatment resulted in earlier vaginal opening time, higher number of Nissl bodies in the hypothalamus neurons, lower apoptosis of hypothalamic cells, higher IGF-1 and GnRH levels in the serum and hypothalamus. DEHP could also upregulated the expression of IGF-1/PI3K/Akt/mTOR pathway and GnRH in the hypothalamus of adolescent female rats, and inhibition of IGF-1R and mTOR in hypothalamus could block the activation of Kiss-1, GPR54, and GnRH by DEHP. In summary, our study suggested that DEHP might activate the hypothalamic GnRH neurons prematurely through the IGF-1 signaling pathway and promote GnRH release, leading to the initiation of female sexual development. Our results provide a new molecular mechanism underlying reproductive and developmental toxicity in pubertal female rats induced by DEHP.
Asunto(s)
Dietilhexil Ftalato/toxicidad , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Pubertad Precoz/inducido químicamente , Transducción de Señal/efectos de los fármacos , Animales , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pubertad Precoz/enzimología , Pubertad Precoz/metabolismo , Ratas , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Activin A (Act A), a member of the transforming growth factor-beta (TGF-ß), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells. In addition, we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy. The activation of JNK and p38 MAPK pathways in OGD-treated PC12 cells was suppressed by exogenous Act A and enhanced by ActRIIA-Ab. Together, our results suggest that Act A/Smads signaling pathway negatively regulates OGD-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.
Asunto(s)
Subunidades beta de Inhibinas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Neuronas/citología , Neuronas/fisiología , Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Autofagia/fisiología , Línea Celular , Supervivencia Celular/fisiología , Estrés Oxidativo/fisiología , Células PC12 , Ratas , Proteínas Smad/metabolismo , Estrés Fisiológico/fisiologíaRESUMEN
BACKGROUND: The atherogenic effect of remnant cholesterol is being increasingly acknowledged. This study aimed to explore the association of discordance between remnant cholesterol and low-density lipoprotein cholesterol with stroke onset using 2 Chinese national cohorts. METHODS AND RESULTS: We studied 11 139 participants from CHARLS (China Health and Retirement Longitudinal Study) and 5993 participants from CHNS (China Health and Nutrition Survey) aged 45 years or older. The discordance between remnant cholesterol and low-density lipoprotein cholesterol was defined using the difference in percentile units (>15 units). There were 988 (8.9%) and 128 (2.1%) stroke events reported during follow-up in the 2 cohorts. Elevated remnant cholesterol was significantly associated with a higher risk of total stroke in 2 cohorts. After adjusting for remnant cholesterol level, the discordantly high remnant cholesterol group was significantly associated with an increased stroke risk (CHARLS: subdistribution hazard ratio [sHR], 1.31 [95 CI, 1.10-1.55]; CHNS: sHR, 1.84 [95 CI, 1.15-3.08]) compared with the discordantly low group. Consistent results were shown even among those with optimal low-density lipoprotein cholesterol level. CONCLUSIONS: The discordance between remnant cholesterol and low-density lipoprotein cholesterol, representing the intraindividual discrepancy, is significantly associated with stroke onset among Chinese adults.
Asunto(s)
LDL-Colesterol , Colesterol , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Persona de Mediana Edad , China/epidemiología , LDL-Colesterol/sangre , Colesterol/sangre , Anciano , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Incidencia , Factores de Riesgo , Biomarcadores/sangre , Encuestas Nutricionales , Medición de Riesgo , Estudios LongitudinalesRESUMEN
Objectives: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture on chemotherapy-induced peripheral neuropathy (CIPN). Methods: We searched for relevant randomized controlled trials (RCTs) in PubMed, Cochrane Library, and Embase databases from their inception to 1 April 2022. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Brief Pain Inventory-Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), Numerical Rating Scale (NRS), and adverse events were the outcome measures. All studies had at least one of these outcome measures. Mean differences (MDs) with 95% confidence intervals (CIs) were assessed in the meta-analysis using the RevMan 5.3 software. Results: Five studies were included in the analysis. The results showed that acupuncture and placebo acupuncture were not significantly different in reducing chemotherapy-induced neurotoxicity and functional disability (random-effects estimates; MD: 4.30; 95% CI: -0.85~9.45; P = 0.10; I2 = 74%). Acupuncture was better than placebo acupuncture in reducing pain severity and pain interference with patients' daily function (fixed-effect estimates; MD: -1.14; 95% CI: 1.87 to -0.42; P = 0.002; I2 = 13%). Acupuncture was not significantly different from placebo acupuncture in relieving CIPN symptoms (MD: -0.81; 95% CI: -2.02 to 0.40, P = 0.19). Acupuncture improved quality of life better than placebo acupuncture (MD: 10.10; 95% CI: 12.34 to 17.86, P = 0.01). No severe adverse events were recorded in all five studies. Conclusion: This meta-analysis suggests that acupuncture may be more effective and safer in reducing pain severity and pain interference with patients' daily function than placebo acupuncture. Additionally, acupuncture may improve the quality of life of patients with CIPN. However, large sample size studies are needed to confirm this conclusion. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324930, identifier: CRD42022324930.
RESUMEN
BACKGROUND: Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis. METHODS: We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs. RESULTS: Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected. CONCLUSION: The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Biología Computacional , Perfilación de la Expresión Génica , Humanos , Pronóstico , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells. MATERIALS AND METHODS: The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays. RESULTS: The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%. CONCLUSION: FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.
Asunto(s)
Proteínas de Ciclo Celular/genética , Ácido Fólico/química , Técnicas de Transferencia de Gen , Polietileneimina/química , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias Gástricas/terapia , Células A549 , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Ácido Fólico/farmacología , Silenciador del Gen , Terapia Genética/métodos , Humanos , Leucina/química , Nanopartículas/química , ARN Interferente Pequeño/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Quinasa Tipo Polo 1RESUMEN
This study aimed to identify prognostic epigenetic biomarkers for colon cancer (CC). Methylation and mRNA expression in CC samples with clinical characteristics that corresponded to those in The Cancer Genome Atlas were analyzed. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were screened between matched tumor and nontumor tissues. Among the 415 DEGs and DMGs that significantly correlated between cytosine-phosphate-guanine (CpG) methylation and gene expression, unc-5 netrin receptor C (UNC5C), solute carrier family 35 member F (SLC35F)1, Ly6/Neurotoxin (LYNX)1, stathmin (STMN)2, slit guidance ligand (SLIT)3, cell adhesion molecule L1 like (CHL1), CAP-Gly domain containing linker protein family member 4 (CLIP4), transmembrane protein (TMEM) 255A, granzyme B (GZMB), and brain expressed X-Linked (BEX)1 were promising epigenetic biomarkers. Prediction was more accurate when models were based on the expression and/or methylation of GZMB rather than clinical stage. Comparisons of tissues with high or low GZMB expression significantly associated the DEGs with natural killer-mediated cytotoxicity, cytokine-cytokine receptor interactions, and chemokine signaling pathways. From among the 10 epigenetic biomarkers, GZMB might serve as a tumor suppressor and function in several immune-related pathways in CC. Prognostic models based on GZMB expression and/or methylation would be significant for patients with CC.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias del Colon/genética , Metilación de ADN/genética , Granzimas/genética , Anciano , Neoplasias del Colon/patología , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Accumulating evidences suggest that miRNAs may prove essential therapeutic targets for the treatment of cancer. Herein, the role and therapeutic implications of miRNA-143 was investigated in gastric cancer. The results revealed miRNA-143 to be aberrantly downregulated in gastric cancer cell lines. Ectopic expression of miRNA-143 resulted in a significant (P<0.05) inhibition of AGS gastric cancer cell proliferation suggestive of the tumor suppressive role of miRNA-143. The inhibition of AGS cell proliferation was mainly via activation of apoptotic cell death as evident from the AO/EB and annexin V/PI staining. Additionally, miR-143 overexpression also caused a significant (P<0.05) decline in the migration and invasion of AGS cells. TargetScan analysis and the dual luciferase assay revealed STAT3 to be the potential target of miRNA-143 in AGS cells. Analysis of STAT3 expression in gastric cancer cell lines showed upto 3.5 fold upregulation of STAT3. However, miRNA-143 overexpression resulted in considerable downregulation of STAT3 expression. Silencing of STAT3 also resulted in the inhibition of cell proliferation, migration and invasion of the AGS cells. Moreover, overexpression of STAT3 could nullify the tumor suppressive effects of miRNA-143 in AGS cells. Taken together, miRNA-143 has a tumor suppressive role in gastric cancer and may prove essential in gastric cancer treatment.
RESUMEN
PURPOSE: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field. MATERIALS AND METHODS: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections. RESULTS: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head. CONCLUSION: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.
Asunto(s)
Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/terapia , Glucocorticoides/efectos adversos , Fenómenos Magnéticos , Nanopartículas de Magnetita/química , Células Madre Mesenquimatosas/citología , Transducción de Señal , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Femenino , Hemólisis/efectos de los fármacos , Humanos , Indoles/química , Nanopartículas de Magnetita/toxicidad , Nanopartículas de Magnetita/ultraestructura , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Polímeros/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Microtomografía por Rayos X , Proteína Letal Asociada a bcl/metabolismoRESUMEN
BACKGROUND: Natural compounds extracted from plants have been reported to have antitumor activity. A fungal metabolite from Phomopsis, identified as epoxycytochalasin H and isolated from the flowering plant Polygonatum sibiricum, was found to have significant antitumor activity. In this study, we report the antitumor effects and mechanism of action of epoxycytochalasin H in the ovarian cancer cell line A2780. Our data suggest that epoxycytochalasin H markedly reduces cell proliferation and induces apoptosis in ovarian cancer cells. MATERIALS AND METHODS: The viability, apoptosis and colony formation of A2780 cells, treated with epoxycytochalasin H, were detected by MTT assay, nuclear staining, flow cytometry, and clone formation assay. MitoROS and mitochondrial membrane potentials were detected by MitoSOX staining and flow cytometry. The expression of proteins associated with apoptosis, autophagy, and endoplasmic reticulum stress, in A2780 cells treated with epoxycytochalasin H, was detected by Western blot. Effects of mitophagy were detected in Parkin-overexpressing 293T cells. RESULTS: Our data suggested that epoxycytochalasin H could strongly reduce cell proliferation and induce apoptosis in ovarian cancer cell line A2780. Epoxycytochalasin H induced apoptosis through mitochondrial injury, mitophagy, and endoplasmic reticulum stress. Specifically, epoxycytochalasin H increased ROS level in cells, and in mitochondria, it decreased mitochondrial membrane potential, caused mitochondrial injury, activated macroautophagy and mitophagy, and subsequently induced apoptosis via the mitochondrial pathway. Additionally, it was discovered that epoxycytochalasin H could induce apoptosis more significantly in 293T cells overexpressing Parkin than in the parental cells. Thus, the mitophagy activated by epoxycytochalasin H could promote apoptosis. In addition, epoxycytochalasin H mediated endoplasmic reticulum stress-related apoptosis. CONCLUSION: Epoxycytochalasin H could promote apoptosis of human ovarian cancer A2780 cells by activating mitochondrial and endoplasmic reticulum stress-related apoptotic pathways.
RESUMEN
The study reports on a case of primary angiosarcoma of the small intestine in a 43-year-old woman presenting with intestinal perforation and metastasis to the peritoneum, along with a pertinent literature review. After hospitalization, an exploratory laparotomy was undertaken to aid in her diagnosis, followed by palliative intestinal resection with enteroenterostomy. The pathological examination and immunohistochemistry of resected tumor tissues confirmed the diagnosis. Moreover, analysis of seven reported cases of primary intestinal angiosarcoma in the literature revealed that patients often present with abdominal pain or recurrent gastrointestinal (GI) bleeding, dying within six months of diagnosis or resection surgery. Altogether, these findings illustrate that, despite volume-reducing palliative surgery, the prognosis of primary angiosarcoma of the small intestine remains poor for the majority of patients.
RESUMEN
Epidemiological studies in recent years have found that the incidence of gastric signet ring cell carcinoma (SRCC) has increased significantly. In this paper, we first reviewed cell origin and biomarkers of SRCC, and the relationship between SRCC and various pathological types of gastric cancer. The early diagnosis rate of gastric SRCC is low, which may be due to the unclear mechanism of pathology and precancerous lesions. In clinical practice, SRCC has the characteristics of low differentiation and high degree of malignancy. Most of patients with gastric cancer Borrmann IV(diffuse infiltrative type) are gastric SRCC, and their prognosis is poor. The average age of gastric SRCC was 55 to 61 years old. Besides, in female, the incidence of SRCC was significantly higher than that of non-SRCC gastric cancer. It is found that the expressions of estrogen and progesterone receptors in SRCC tissues are high. The relationship between gastric SRCC and sex hormones may be the cause of gender differences in the pathogenesis of gastric SRCC. Due to the low risk of lymph node metastasis in early SRCC, endoscopic mucosal resection and endoscopic submucosal dissection can be performed for <3 cm, submucosal invasive, medium differentiated tumors, or <3 cm, highly differentiated, ulcerative and submucosal lesions. For non-metastatic advanced gastric SRCC, surgical resection and adequate lymph node dissection should be performed owing to the high risk of lymph node metastasis. Adjuvant chemotherapy is also considered to improve the long-term prognosis of patients. Taxane therapy may be more effective in gastric SRCC. Recent data show that gastric SRCC and diffuse gastric cancer are more sensitive to mitomycin C, doxorubicin and docetaxel than intestinal type gastric cancer, but are not sensitive to fluorouracil and cisplatin. These treatment perspectives still need to be confirmed in future studies.