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BACKGROUND: Myoblasts play an important role in muscle growth and repair, but the high glucose environment severely affects their function. The purpose of this study is to explore the potential molecular mechanism of liraglutide in alleviating the effects of high glucose environments on myoblasts. METHODS: MTT, western blot, and ELISA methods were used to investigate the role of liraglutide on C2C12 myoblasts induced by high glucose. The high-throughput transcriptome sequencing technique was used to sequence C2C12 myoblasts from different treated groups. The DESeq2 package was used to identify differentially expressed-mRNAs (DE-mRNAs). Then, functional annotations and alternative splicing (AS) were performed. The Cytoscape-CytoHubba plug-in was used to identify multicentric DE-mRNAs. RESULTS: The MTT assay results showed that liraglutide can alleviate the decrease of myoblasts viability caused by high glucose. Western blot and ELISA tests showed that liraglutide can promote the expression of AMPKα and inhibit the expression of MAFbx, MuRF1 and 3-MH in myoblasts. A total of 15 multicentric DE-mRNAs were identified based on the Cytoscape-CytoHubba plug-in. Among them, Top2a had A3SS type AS. Functional annotation identifies multiple signaling pathways such as metabolic pathways, cytokine-cytokine receptor interaction, cAMP signaling pathway and cell cycle. CONCLUSION: Liraglutide can alleviate the decrease of cell viability and degradation of muscle protein caused by high glucose, and improves cell metabolism and mitochondrial activity. The molecular mechanism of liraglutide to alleviate the effect of high glucose on myoblasts is complex. This study provides a theoretical basis for the clinical effectiveness of liraglutide in the treatment of skeletal muscle lesions in diabetes.
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Liraglutida , Transcriptoma , Liraglutida/farmacología , Liraglutida/metabolismo , Músculo Esquelético/metabolismo , Glucosa/farmacología , Glucosa/metabolismo , MioblastosRESUMEN
The signal transducer and activator of transcription 3 (STAT3) has been established as a crucial drug target in the development of antitumor agents. In this study, a series of 21 derivatives of the STAT3 inhibitor napabucasin were designed and synthesized. Through preliminary screening against tumor cell lines, SZ6 emerged as the most potent compound with half maximal inhibitory concentration (IC50) values of 46.3 nM, 66.4 nM, and 53.8 nM against HCT116, HepG2, and Hela cells respectively. Furthermore, SZ6 effectively suppressed tumor invasion and migration in HCT116 cell assays by inducing S-phase arrest and apoptosis through inhibition of Protein Kinase B (PKB/AKT) activity and induction of reactive oxygen species (ROS). The mechanism underlying SZ6's action involves inhibition of STAT3 phosphorylation, which was confirmed by western blotting analysis. Additionally, surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA) demonstrated direct binding between SZ6 and STAT3. Notably, in vivo studies revealed that SZ6 significantly inhibited tumor growth without any observed organ toxicity. Collectively, these findings identify SZ6 as a promising STAT3 inhibitor for colorectal cancer treatment.
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Antineoplásicos , Apoptosis , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Factor de Transcripción STAT3 , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Animales , Tiazoles/farmacología , Tiazoles/química , Tiazoles/síntesis química , Ratones , Naftoquinonas/farmacología , Naftoquinonas/síntesis química , Naftoquinonas/química , Ratones Desnudos , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , BenzofuranosRESUMEN
The activating receptor natural killer group 2D (NKG2D) expressed by Natural killer (NK) cells functions as a "master-switch" in governing the awakening status of NK cells. The NKG2D-mediated cytotoxicity has been declared to be related with the expression levels of NKG2D ligands (NKG2DLs) expressed on tumor cells. Therefore, selective induction of NKG2DLs could be a reliable approach to enhance the efficacy of NK cell-mediated immunotherapy. Our existing study demonstrated that Ciclopirox Olamine (CPX), an off-patent antifungal agent, effectively elevated the expression of NKG2DLs on leukemia cells and sensitized leukemia cells to NK-cell mediated cytolysis. Induction of ROS production and AKT phosphorylation by CPX is essential for the up-regulation of NKG2DLs expressions. Inhibition of AKT by using AKT inhibitor MK2206 decreased both NKG2DLs expressions and NK cell cytotoxicity. These data indicated that increased sensitivity of CPX-treated leukemia cells to NK cell cytolysis was attributed to higher NKG2DLs expressions, resulting from activated AKT signaling pathway. Our findings support the ongoing development of CPX as an anti-tumor agent and suggest its promising immunotherapeutic value in the medication of leukemia.
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Leucemia , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ciclopirox/farmacología , Ciclopirox/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Células Asesinas Naturales/metabolismo , Transducción de Señal , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Línea Celular TumoralRESUMEN
As a preferred nitrogen form, ammonium (NH4 + ) transport via specific transporters is particularly important for the growth and development of tea plants (Camellia sinensis L.). However, our understanding of the functions of the AMT family in tea plants is limited. We identified and named 16 putative AMT genes according to phylogenetic analysis. All CsAMT genes were divided into three groups, distributed on 12 chromosomes with only one segmental duplication repetition. The CsAMT genes showed different expression levels in different organs, and most of them were expressed mainly in the apical buds and roots. Complementation analysis of yeast mutants showed that CsAMTs restored the uptake of NH4 + . This study provides insights into the genome-wide distribution and spatial expression of AMT genes in tea plants.
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Compuestos de Amonio , Camellia sinensis , Compuestos de Amonio/metabolismo , Camellia sinensis/genética , Camellia sinensis/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Té/metabolismoRESUMEN
BACKGROUND: Irisin is a novel myokine both in mice and humans, and it can also be secreted by adipose tissue and the liver in a small amounts. There are few studies on irisin and bone metabolism. The aim of this study was to assess the relationship between serum irisin levels and bone metabolism and analyze its related factors in Han young male with pre-diabetic individuals. METHODS: This cross-sectional study included 41 pre-diabetes and 45 normal glucose tolerance (NGT). Anthropometric measurements, including height, weight, waist circumference (WC), and bone mineral content (BMC), were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 h of fasting, and the levels of glucose, insulin, lipids, serum irisin and bone turnover markers were measured. RESULTS: The levels of serum irisin (4.4 ± 1.4 vs. 6.3 ± 1.5 µg/mL), P1NP and OC were significantly lower and CTX was significantly higher in the pre-diabetes group (P < 0.05). BMC did not differ in the two groups (P > 0.05). Serum irisin levels negatively correlated with BMI (r =-0.325), FPG (r =-0.329), TG (r =-0.339) (P < 0.05) in NGT individuals. Serum irisin levels positively correlated with P1NP (r = 0.398), OC (r = 0.351), HDL-C (r = 0.432) and negatively correlated with FPG (r = -0.725), 2 h-PG (r = -0.360) (P < 0.05) in pre-diabetic individuals. Multiple regression analysis revealed that Serum irisin (ß = 9.768, P = 0.025) and WC (ß = -2.355, P = 0.002) were significant independent predictors for P1NP. CONCLUSION: Bone turnover markers were changed rather than bone mineral content in young men with pre-diabetes. In pre-diabetes individuals, serum irisin levels were reduced and close relationship with P1NP. Falling irisin levels may be a predictor of decreased bone formation in Han young men with pre-diabetes individuals.
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Estado Prediabético , Humanos , Masculino , Ratones , Animales , Estado Prediabético/diagnóstico , Fibronectinas , Estudios Transversales , Glucosa , China/epidemiologíaRESUMEN
Colorectal cancer stem cells (CCSCs) are implicated in colorectal tumor initiation, invasion, recurrence and treatment resistance, so elucidation of the mechanism underlying the cancer stem cells induction and development of drugs targeting CCSCs are vital for cancer treatment. Growing evidence shows that dysregulated deubiquitinase (DUBs) expression is frequently associated with stemness and maintenance of cancer stem cells (CSCs). In the current study, we found that upregulation of USP47 is associated with tumorigenesis and poor prognosis in clinical patients with colorectal cancer (CRC). Besides, USP47 was highly expressed in CCSCs enriched by serum-free culture. Further investigation showed that USP47 is closely involved in the maintenance of the stemness of CCSCs. USP47 silencing reduces proliferation and migration of colorectal cancer cells and suppresses the self-renewal of CCSCs by downregulating the expression of cancer stem cell markers, including CD44, CD133, CD166, OCT4 and NANOG. Furthermore, we identified Parthenolide (PTL), a natural sesquiterpene lactone, as a novel USP47 inhibitor. PTL diminishes CCSCs self-renewal and induces apoptosis of CCSCs. Taken together, our ï¬ndings highlighted a novel DUB involved in the modulation of CCSCs stemness and the potential of PTL in the CRC treatment by targeting CCSCs as the USP47 inhibitor.
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Neoplasias Colorrectales/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Sesquiterpenos/farmacología , Ubiquitina Tiolesterasa/metabolismo , Apoptosis/efectos de los fármacos , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Pronóstico , Unión Proteica/efectos de los fármacos , Ubiquitina Tiolesterasa/genética , Proteasas Ubiquitina-Específicas , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Cancer has always been one of the most common malignant diseases in the world. Therefore, there is an urgent need to find potent agents with selective antitumor activity against cancer cells. It has been reported that antimicrobial peptides (AMPs) can selectively target tumor cells. In this study, we focused on the anti-tumor activity and mechanism of Brevinin-1RL1, a cationic α-helical AMP isolated from frog Rana limnocharis skin secretions. We found that Brevinin-1RL1 preferentially inhibits tumor cells rather than non-tumor cells with slight hemolytic activity. Cell viability assay demonstrated the intermolecular disulfide bridge contributes to the inhibitory activity of the peptide as the antitumor activity was abolished when the disulfide bridge reduced. Further mechanism studies revealed that both necrosis and apoptosis are involved in Brevinin-1RL1 mediated tumor cells death. Moreover, Brevinin-1RL1 induced extrinsic and mitochondria intrinsic apoptosis is caspases dependent, as the pan-caspase inhibitor z-VAD-FMK rescued Brevinin-1RL1 induced tumor cell proliferative inhibition. Immunohistology staining showed Brevinin-1RL1 mainly aggregated on the surface of the tumor cells. These results together suggested that Brevinin-1RL1 preferentially converges on the cancer cells to trigger necrosis and caspase-dependent apoptosis and Brevinin-1RL1 could be considered as a pharmacological candidate for further development as anti-cancer agent.
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Apoptosis , Proteínas Citotóxicas Formadoras de Poros/farmacología , Ranidae/metabolismo , Piel/química , Secuencia de Aminoácidos , Animales , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Línea Celular Tumoral , Hemólisis/efectos de los fármacos , Concentración 50 Inhibidora , Peso Molecular , Necrosis , Proteínas Citotóxicas Formadoras de Poros/síntesis química , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/aislamiento & purificación , Agregado de Proteínas/efectos de los fármacosRESUMEN
Microtubules are involved in celluar processes of movement, intracellular trafficking and mitosis, thus microtubule-targeting agents have been widely used in cancer therapy. Herein, we report isopenicin A, a novel meroterpenoid isolated from the plant endophytic fungus of Penicillium sp. sh18, as a novel microtubule binding molecule that efficiently depolymerizes microtubule polymerization to evoke G2/M cell cycle arrest and subsequent cell apoptosis, contributing to proliferation inhibition of human tumor cell lines. The discovery of isopenicin A provides a new chemotype for discovery and development of promising microtubule inhibitors.
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Antineoplásicos/aislamiento & purificación , Penicillium/química , Moduladores de Tubulina/aislamiento & purificación , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Microtúbulos/metabolismo , Polimerizacion/efectos de los fármacos , Terpenos/aislamiento & purificación , Terpenos/farmacología , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologíaRESUMEN
Tea is an important beverage in humans' daily lives. For a long time, tea grade identification relied on sensory evaluation, which requires professional knowledge, so is difficult and troublesome for laypersons. Tea chemical component detection usually involves a series of procedures and multiple steps to obtain the final results. As such, a simple, rapid, and reliable method to judge the quality of tea is needed. Here, we propose a quick method that combines ultraviolet (UV) spectra and color difference to classify tea. The operations are simple and do not involve complex pretreatment. Each method requires only a few seconds for sample detection. In this study, famous Chinese green tea, Huangshan Maofeng, was selected. The traditional detection results of tea chemical components could not be used to directly determine tea grade. Then, digital instrument methods, UV spectrometry and colorimetry, were applied. The principal component analysis (PCA) plots of the single and combined signals of these two instruments showed that samples could be arranged according to grade. The combined signal PCA plot performed better with the sample grade descending in clockwise order. For grade prediction, the random forest (RF) model produced a better effect than the support vector machine (SVM) and the SVM + RF model. In the RF model, the training and testing accuracies of the combined signal were all 1. The grades of all samples were correctly predicted. From the above, the UV spectrum combined with color difference can be used to quickly and accurately classify the grade of Huangshan Maofeng tea. This method considerably increases the convenience of tea grade identification.
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Análisis de los Alimentos/métodos , Espectrofotometría Ultravioleta/métodos , Té/química , Camellia sinensis/química , Color , Análisis de los Alimentos/estadística & datos numéricos , Humanos , Análisis de Componente Principal , Espectrofotometría Ultravioleta/estadística & datos numéricos , Máquina de Vectores de Soporte , GustoRESUMEN
This paper proposes two spatio-temporal epidemic network models based on popularity and similarity optimization (PSO), called r-SI and r-SIS, respectively, in which new connections take both popularity and similarity into account. In the spatial dimension, the epidemic process is described by the diffusion equation; in the time dimension, the growth of an epidemic is described by the logistic map. Both models are represented by partial differential equations, and can be easily solved. Simulations are performed on both artificial and real networks, demonstrating the effectiveness of the two models.
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Simulación por Computador , Epidemias , Modelos Biológicos , Redes Neurales de la Computación , HumanosRESUMEN
It is very difficult for humans to distinguish between two kinds of black tea obtained with similar processing technology. In this paper, an electronic tongue was used to discriminate samples of seven different grades of two types of Chinese Congou black tea. The type of black tea was identified by principal component analysis and discriminant analysis. The latter showed better results. The samples of the two types of black tea distributed on the two sides of the region graph were obtained from discriminant analysis, according to tea type. For grade discrimination, we determined grade prediction models for each tea type by partial least-squares analysis; the coefficients of determination of the prediction models were both above 0.95. Discriminant analysis separated each sample in region graph depending on its grade and displayed a classification accuracy of 98.20% by cross-validation. The back-propagation neural network showed that the grade prediction accuracy for all samples was 95.00%. Discriminant analysis could successfully distinguish tea types and grades. As a complement, the models of the biochemical components of tea and electronic tongue by support vector machine showed good prediction results. Therefore, the electronic tongue is a useful tool for Congou black tea classification.
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Camellia sinensis/química , Nariz Electrónica , Redes Neurales de la Computación , Máquina de Vectores de Soporte , Té/química , HumanosRESUMEN
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy.
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Complejo CD3/inmunología , Carcinoma Hepatocelular/terapia , Inmunoterapia/métodos , Neoplasias Hepáticas/terapia , Anticuerpos de Cadena Única/inmunología , Cordón Umbilical/citología , Adenoviridae/genética , Adenoviridae/fisiología , Animales , Citotoxicidad Celular Dependiente de Anticuerpos , Antimetabolitos Antineoplásicos/farmacología , Complejo CD3/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/virología , Membrana Celular/inmunología , Movimiento Celular , Fluorouracilo/farmacología , Vectores Genéticos , Xenoinjertos , Humanos , Lentivirus/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/virología , Linfocitos/inmunología , Células Madre Mesenquimatosas/inmunología , Ratones , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/metabolismo , Factores de Tiempo , Replicación Viral , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , alfa-Fetoproteínas/genéticaRESUMEN
Objective To investigate the effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain. Methods Our study selected 100 clean grade healthy Sprague-Dawley adult male rats weighing 200 to 250 g. After establishment of a rat model of chronic constriction injury, these rats were divided into 10 groups (10 rats in each group): the normal control, sham operation, chronic constriction injury, normal saline, morphine, miR-223, NLRP3, miR-223 + morphine, NLRP3 + morphine, and miR-223 + NLRP3 + morphine groups. The real-time quantitative polymerase chain reaction assay, Western blotting, and enzyme-linked immunosorbent assay were used for detecting the mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, Interleukin (IL)-1ß, and IL-18 in sections of lumbar spinal cord. Immunohistochemistry was applied for detecting the positive rates of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1ß, and IL-18. Results The paw withdrawal threshold and percentage maximum possible effect (%MPE) were higher in chronic constriction injury group when compared with the normal control and sham operation groups. Behavioral tests showed that compared with the chronic constriction injury and normal saline groups, the morphine and miR-223 + morphine groups showed obvious analgesic effects. Expressions of miR-223 in the miR-223, miR-223 + morphine, and miR-223 + NLRP3 + morphine were significantly higher than those in the chronic constriction injury, normal saline, and morphine groups. Compared with chronic constriction injury, normal saline and morphine groups, the mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1ß, and IL-18 were significantly decreased in the miR-223 and miR-223 + morphine groups, while mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1ß, and IL-18 were significantly increased in the NLRP3 and NLRP3 + morphine group. Conclusion Our study provides strong evidence that miR-223 could suppress the activities of NLRP3 inflammasomes ( NLRP3, apoptosis-associated speck-like protein, and Caspase-1) to relieve morphine analgesic tolerance in rats by down-regulating NLRP3.
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MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Analgésicos Opioides/uso terapéutico , Animales , Inmunohistoquímica , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , MicroARNs/genética , Morfina , ARN Mensajero/metabolismo , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Neuropathic pain is a type of chronic pain that results from dysfunctions of the somatosensory nerve system. This study was aimed to investigate the effect of mTOR/VEGF signaling pathway on neuropathic pain and the regulation mechanisms of miR-183 on AMPA Receptors through mTOR/VEGF signaling pathway. METHODS: Chronic compress injury (CCI) model was constructed in the current study, we used paw withdrawal mechanic threshold (PWMT) and paw withdrawal thermal latency (PWTL) to observe mTOR and VEGF receptors. Dual luciferase analysis, western blot and qRT-PCR were also applied to complete this experiment. RESULTS: It was observed that the inhibition of mTOR and VEGF receptors could significantly relieve neuropathic pain in the CCI model. Moreover mTOR was confirmed as the direct target of miR-183. Furthermore, miR-183 could modulate VEGF through regulating mTOR expressions. We also found the expressions of AMPA receptors (i.e. GluR1 and GluR2), located in the downstream of mTOR/VEGF signaling pathway, were significantly upregulated when miR-183 was downregulated or when the mTOR/VEGF signaling pathway was activated. CONCLUSION: The inhibition of mTOR or VEGF receptors can significantly relieve neuropathic pain, and the upregulation of miR-183 can suppress AMPA receptors by inhibiting mTOR/VEGF pathway.
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MicroARNs/metabolismo , Neuralgia/patología , Receptores AMPA/metabolismo , Regiones no Traducidas 3' , Animales , Secuencia de Bases , Modelos Animales de Enfermedad , Regulación hacia Abajo , Inmunohistoquímica , Masculino , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Neuralgia/metabolismo , Oligonucleótidos/química , Oligonucleótidos/metabolismo , Células PC12 , Ratas , Ratas Sprague-Dawley , Receptores AMPA/genética , Alineación de Secuencia , Transducción de Señal , Médula Espinal/metabolismo , Médula Espinal/patología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: The aim of this study was to evaluate serum irisin levels and analyze its related factors in Han adults with metabolically healthy obesity. METHODS: This cross-sectional study included 75 metabolically healthy, non-obese adults and 51 metabolically healthy, obese adults. Anthropometric measurements, including height, weight, waist circumference (WC), and blood pressure, were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 hours of fasting, and the levels of glucose, insulin, lipids, and serum irisin were measured. RESULTS: The levels of serum irisin (5.40 ± 1.69 vs. 6.46 ± 1.37 µg/mL) were significantly lower in the metabolically healthy obese group (p < 0.05). Irisin correlated positively with high density lipoprotein cholesterol (HDL-C) (r = 0.303) and correlated negatively with body mass index (BMI) (r = -0.389), WC (r = -0.324), fasting plasma glucose (FPG) (r = -0.441), HOMA-IR (r = -0.429), triglycerides (TG) (r = -0.185), total cholesterol (TC) (r = -0.209), low density lipoprotein cholesterol (LDL-C) (r = -0.157) (p < 0.05). Multiple regression analysis revealed that FPG (ß = -1.720, p = 0.001) and HOMA-IR (ß = -0.399, p = 0.006) were still significantly associated with irisin. Serum irisin (ß = -0.246, p = 0.005) and BMI (ß = 0.078, p = 0.043) were significant independent predictors for HOMAIR. CONCLUSIONS: Serum irisin levels were reduced in metabolically healthy, obese Han adults. Irisin reduction appears to be associated with elevated FPG and insulin resistance but not obesity. In additional, falling irisin may increase the occurrence of insulin resistance in metabolically healthy Han adults and should be examined in future studies.
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Fibronectinas/sangre , Resistencia a la Insulina , Obesidad Metabólica Benigna , Adulto , Glucemia , Índice de Masa Corporal , Estudios Transversales , Humanos , Insulina , ObesidadRESUMEN
OBJECTIVE: MicroRNAs have been reported to play an important role in the invasion and metastasis of cervical cancer. miR-183 was found to inhibit or promote the invasion and metastasis of multiple solid tumors. However, the roles of miR-183 in cervical cancer are unclear. METHODS: In this study, miR-183 expression levels were measured in 53 cervical cancer and 13 normal cervical tissues by qRT-PCR. The effects of forced expression of miR-183 on cervical cancer cells invasion and metastasis were investigated using Transwell uncoated or coated with growth factor-reduced Matrigel for migration or invasion assays, respectively. RESULTS: We found that miR-183 expression levels were significantly down-regulated in cervical cancer tissues compared with normal tissues (0.15±0.011 to 0.86±0.049). Ectopic expression of miR-183 resulted in the suppression of invasion and migration of cervical cancer cell lines, siha and Hela cells (p<0.0001). Bioinformatics analysis revealed that MMP-9 was the potential target of miR-183 and it was found that MMP-9 was remarkably up-regulated in cervical cancer. Furthermore, a dual-luciferase reporter assay showed that MMP-9 as a target of miR-183 (p<0.0001). The invasion and metastasis ability of siha and Hela was suppressed when MMP-9 was down-regulated in vitro (p<0.0001). CONCLUSIONS: In conclusion, our study revealed that miR-183 might be a tumor suppressor via inhibiting the invasion and metastasis of cervical cancer cells through targeting MMP-9, indicating that miR-183 may be a novel potential therapeutic target for cervical cancer.
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Genes Supresores de Tumor/fisiología , Metaloproteinasa 9 de la Matriz/genética , MicroARNs/fisiología , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Movimiento Celular , Biología Computacional , Femenino , Humanos , Metaloproteinasa 9 de la Matriz/análisis , MicroARNs/análisis , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias del Cuello Uterino/mortalidadRESUMEN
Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant to chemotherapeutic agents, thus playing an important role in multidrug resistance. As there is a clear association between drug resistance and an aggressive phenotype, we asked whether sorcin affects also the motility, invasion, and stem cell characteristics of cancer cells. We have used both RNA interference (transient and stable expression of hairpins) and a lentiviral expression vector to experimentally modulate sorcin expression in a variety of cells. We demonstrate that sorcin depletion in MDA-MB-231 breast cancer cells reduces the pool of CD44(+)/CD24(-) and ALDH1(high) cancer stem cells (CSCs) as well as mammosphere-forming capacity. We also observe that sorcin regulates epithelial-mesenchymal transition and CSCs partly through E-cadherin and vascular endothelial growth factor expression. This leads to the acquisition of an epithelial-like phenotype, attenuating epithelial-mesenchymal transition and suppression of metastases in nude mice. The sorcin-depleted phenotype can also be reproduced in lung adenocarcinoma A549 cells and lung fibrosarcoma HT1080 cells. In addition, overexpression of sorcin in MCF7 cells, which have low endogenous sorcin expression levels, increases their migration and invasion in vitro. This offers the rationale for the development of therapeutic strategies down-regulating sorcin expression for the treatment of cancer.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias de la Mama/genética , Proteínas de Unión al Calcio/genética , Transición Epitelial-Mesenquimal/genética , Fibrosarcoma/secundario , Neoplasias Pulmonares/secundario , Adenocarcinoma/genética , Adenocarcinoma del Pulmón , Familia de Aldehído Deshidrogenasa 1 , Animales , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Antígeno CD24/biosíntesis , Movimiento Celular/genética , Proliferación Celular , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Etopósido/uso terapéutico , Femenino , Fibrosarcoma/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Receptores de Hialuranos/biosíntesis , Isoenzimas/biosíntesis , Neoplasias Pulmonares/genética , Células MCF-7 , Ratones , Ratones Desnudos , Invasividad Neoplásica/genética , Neovascularización Patológica/genética , Interferencia de ARN , ARN Interferente Pequeño , Retinal-Deshidrogenasa/biosíntesis , Esferoides Celulares/citología , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
The incidence of stage Ib~IIa of cervical adenocarcinoma accounts about 60 to 70% of all patients. This study aims to investigate the prognostic significance of protein estrogen receptor alpha (ERα) and transforming growth factor beta 1 (TGF-ß1) level in different glandular epithelia of the cervix. In this study, immunohistochemistry was used to detect ERα and TGF-ß1 in carcinomas and incisal margins of 66 cases with cervical adenocarcinoma, 20 cases with normal cervix, and 20 cases with chronic cervicitis. Uni- and multivariate analysis was applied to evaluate the prognostic significance of TGF-ß1 and ERα in carcinomas. The results indicated that the positive expression of TGF-ß1 in carcinomas was 71.21%, significantly higher compared to that in the normal cervix (35%) and chronic cervicitis (55%) (χ(2) = 8.901, P = 0.012). Similarly, the positive expression of ERα in the carcinomas was 68.18%, significantly higher compared to the normal cervix (35%) and chronic cervicitis (50%) (χ(2) = 7.693, P = 0.021). Both TGF-ß1 and ERα in the carcinomas were associated with the vaginal recurrence, infection of HPV, depth of infiltration, and lymphatic metastasis (P < 0.05). The conjugation of TGF-ß1 and ERα was an independent prognostic factor for cervical adenocarcinoma. Survival curve showed that the positive TGF-ß1 and ERα indicated a short lifetime of patient with cervical adenocarcinoma. In conclusion, the expression of TGF-ß1 and ERα protein in the carcinomas had a significant prognostic value in a patient of stage Ib~IIa in cervical adenocarcinoma.