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Herein we report that Ti3AlC2 MXene nanosheets were identified as a highly effective cathodic protection corrosion inhibitor for carbon steel in hydrochloric acid solution. Ti3AlC2 Mxene nanosheets form a stable inhibition layer on metal surfaces due to their high adsorption capacity and act as a barrier or protective film to prevent attacks from corrosive substances and thus lead to an extended metal service life.
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OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.
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Carbapenémicos , Unidades de Cuidados Intensivos , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Prevalencia , Estudios Prospectivos , Factores de RiesgoRESUMEN
To explore the effects of an improved perioperative management model on the mental state, quality of life, and self-care ability scores of patients after radical prostatectomy. Overall, 96 postoperative prostate cancer patients admitted to our hospital between November 2019 and May 2021 were retrospectively analyzed and classified into an observation group and a control group with 48 patients each, according to the management model they received. The patients in the control group received routine care and were discharged. The observation group implemented an improved perioperative management model than the control group. Differences in mental state, quality of life, and self-care ability scores between the 2 groups were compared. After nursing, the self-rating anxiety scale and self-rating depression scale scores of the 2 groups were significantly lower than those before nursing, and the observation group's self-rating anxiety scale and self-rating depression scale scores were significantly lower than those of the control group (Pâ <â .05). Regarding emotion, cognition, and society, the observation group's quality of life scores was significantly higher than those of the control group. In contrast, overall health was significantly lower than that of the control group (Pâ <â .05). After nursing, the observation group's self-care skills, self-responsibility, health knowledge, and self-concept scores were significantly better than those of the control group (Pâ <â .05). The improved prostate cancer perioperative management model helps improve patients' unhealthy mental state, quality of life, self-care ability, and provides guidelines for the clinical care of patients after prostate cancer surgery.
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Neoplasias de la Próstata , Calidad de Vida , Masculino , Humanos , Estudios Retrospectivos , Autocuidado , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugíaRESUMEN
Background: This study analyzed both the influencing factors of malnutrition in patients with gastric cancer and established a multi-dimensional risk model to predict postoperative malnutrition three months after surgery. Methods: The clinical data of gastric cancer patients hospitalized for the first time and receiving laparoscopic surgery in the general surgery department of our hospital were retrospectively analyzed through the hospital information system and divided into a training set and a validation set in the ratio of 7:3. Nutritional status was assessed using the Patient Generated Subjective Global Assessment scale and follow-up records three months after surgery. Patients were divided into a non-malnutrition group and a malnutrition group, and a risk prediction model was established and displayed in the form of a nomogram. Results: A total of 344 patients were included, with 242 in the training and 102 in the validation set. Tumor node metastasis stage (TNM Stage, P=0.020), cardiac function grading (CFG, P=0.013), prealbumin (PAB, P<0.001), neutrophil-to-lymphocyte ratio (NLR, P=0.027), and enteral nutrition within 48 hours post-operation (EN 48 h post-op, P=0.025) were independent risk factors. We established a prediction model with the above variables and displayed it via a nomogram, then verified its effectiveness through internal and external verification. This revealed a C-index of 0.84 (95% CI: 0.79-0.89), and the area under curve (AUC) areas of 0.840 (training set) and 0.854 (validation set), which was better than the nutritional risk screening 2002 (NRS2002) scale. The calibration curve brier scores were 0.159 and 0.195, and the Hosmer-Lemeshow test chi-square values were 14.070 and 1.989 (P>0.05). The decision curve analysis (DCA) of the training set model indicated the clinical applicability was good and within the threshold probability range of 10%-85%, which was also better than NRS2002. Conclusions: A clinical prediction model including multi-dimensional variables was established based on independent risk factors of malnutrition three months after gastrectomy in patients with gastric cancer. The model yields greater prediction accuracy of the risk of three-month-postoperative malnutrition in patients with gastric cancer, helps screen high-risk patients, formulates targeted nutritional prescriptions early, and improves the overall prognosis of patients.
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Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data shown in Figs. 2C, 4C and 5C, and the cell invasion assay data shown in Figs. 2D and E, 4D and E and 5D and E were strikingly similar to data appearing in different form in other articles by different authors. In addition, the authors independently contacted the Editorial Office to request that this paper be retracted owing to the fact that they had not obtained approval from the Ethics Committee of The Second Affiliated Hospital of Harbin Medical University to use the tissue samples, even though they had written that this study was approved by the Ethics Committee, and written informed consent had been provided by all patients enrolled in the research. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, and the authors' own admission of serious problems concerning the ethical nature of the study, the Editor has decided that this paper should be retracted from the Journal. The authors have agreed to the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 38903898, 2018; DOI: 10.3892/or.2018.6763].
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The infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein-protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.
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Neoplasias Gástricas , Microambiente Tumoral , Proteínas ADAMTS/metabolismo , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Pronóstico , Células del Estroma/metabolismoRESUMEN
OBJECTIVES: The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. METHODS: The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein-protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. RESULTS: The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. CONCLUSIONS: The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Ciclina B1/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Pronóstico , Microambiente TumoralRESUMEN
MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit8 and colony formation assays. Suppression of miR92a inhibited SGC7901 cell proliferation as determined by Ki67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR92a. Downregulation of miR92a significantly increased ING2 expression at the mRNA and protein levels. A dualluciferase reporter assay validated a direct binding site of miR92a on ING2. In addition, SGC7901 cells with suppression of miR92a were more sensitive to doxorubicin treatment. Knockdown of miR92a reduced the halfmaximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.
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Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Proteínas de Homeodominio/genética , MicroARNs/genética , Receptores Citoplasmáticos y Nucleares/genética , Neoplasias Gástricas/genética , Proteínas Supresoras de Tumor/genética , Regiones no Traducidas 3' , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Long non-coding RNA H19 (H19) plays an important role by regulating protein expression in different tissues and organs of the body. However, whether H19 induces hypoxia/reoxygenation (h/R) injury via increase of autophagy in the hepatoma carcinoma cells is unknown. RESULTS: H19 was expressed in the hepatoma carcinoma cells (Hep G2 and HCCLM3 cells) and its expression was most in 8 h/24R. The knockdown of H19 and 3-MA (an autophagy inhibitor) protected against h/R-induced apoptosis, cell damage, the expression of cleaved caspase-3 and cleaved caspase-9, the release of cytochrome c (Cyt c). The knockdown of H19 and 3-MA also decreased the autophagic vesicles (AVs) and the expression of Beclin-1 and the ration of LC3-II/LC3-I, and increased cell viability, the expression of Bcl-2 and P62 and the phosphorylation of PI3K, Akt and mTOR. In addition, chloroquine (CQ, an inhibitor of autophagy flux) markedly decreased formation of autophagy flux (the ration of LC3-II/LC3-I). The results of the knockdown of H19 group were similar to those of the 3-MA (or CQ) group. Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. The knockdown of H19 cancelled the effect of rapamycin. The overexpression of H19 further expanded h/R-induced increase of the ration of LC3-II/LC3-I and decrease of the phosphorylated PI3K, Akt and mTOR. CONCLUSIONS: Our results suggest that the long non-coding RNA H19 induces h/R injury by up-regulation of autophagy via activation of PI3K-Akt-mTOR pathway in the hepatoma carcinoma cells.
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Carcinoma Hepatocelular/metabolismo , Hipoxia/metabolismo , Neoplasias Hepáticas/metabolismo , ARN Largo no Codificante/metabolismo , Daño por Reperfusión/metabolismo , Apoptosis/fisiología , Autofagia/efectos de los fármacos , Isquemia Encefálica/metabolismo , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Oxígeno/metabolismo , Regulación hacia Arriba/fisiologíaRESUMEN
BACKGROUND: Long non-coding RNA H19 (H19) plays an important role by regulating protein expression in different tissues and organs of the body. However, whether H19 induces hypoxia/reoxygenation (h/R) injury via increase of autophagy in the hepatoma carcinoma cells is unknown. RESULTS: H19 was expressed in the hepatoma carcinoma cells (Hep G2 and HCCLM3 cells) and its expression was most in 8 h/24R. The knockdown of H19 and 3-MA (an autophagy inhibitor) protected against h/R-induced apoptosis, cell damage, the expression of cleaved caspase-3 and cleaved caspase-9, the release of cytochrome c (Cyt c). The knockdown of H19 and 3-MA also decreased the autophagic vesicles (AVs) and the expression of Beclin-1 and the ration of LC3-II/LC3-I, and increased cell viability, the expression of Bcl-2 and P62 and the phosphorylation of PI3K, Akt and mTOR. In addition, chloroquine (CQ, an inhibitor of autophagy flux) markedly decreased formation of autophagy flux (the ration of LC3-II/LC3-I). The results of the knockdown of H19 group were similar to those of the 3-MA (or CQ) group. Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. The knockdown of H19 cancelled the effect of rapamycin. The overexpression of H19 further expanded h/R-induced increase of the ration of LC3-II/LC3-I and decrease of the phosphorylated PI3K, Akt and mTOR. CONCLUSIONS: Our results suggest that the long non-coding RNA H19 induces h/R injury by up-regulation of autophagy via activation of PI3K-Akt-mTOR pathway in the hepatoma carcinoma cells.
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Humanos , Daño por Reperfusión/metabolismo , Carcinoma Hepatocelular/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias Hepáticas/metabolismo , Hipoxia/metabolismo , Oxígeno/metabolismo , Autofagia/efectos de los fármacos , Regulación hacia Arriba/fisiología , Isquemia Encefálica/metabolismo , Apoptosis/fisiología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patologíaRESUMEN
Numerous microRNAs (miRNAs) have been demonstrated to be downregulated or upregulated in hepatocellular carcinoma (HCC) and play important roles in its occurrence and development. Therefore, the investigation of miRNAs and their functions implicated in the genesis and development of HCC may provide key clues for the identification of effective therapeutic approaches for patients with this disease. The aims of the present study were to detect miRNA466 (miR466) expression in HCC tissues and cell lines and to determine its effects on HCC cell proliferation, apoptosis and metastasis, as well as to explore the mechanisms underlying the tumorsuppressing roles of miR466 in HCC. In the present study, reverse transcriptionquantitative polymerase chain reaction (RTqPCR) was performed to detect miR466 expression in HCC tissues and cell lines. The effects of miR466 upregulation on HCC cell proliferation, apoptosis, migration and invasion were determined using Cell Counting Kit8 assay, flow cytometry analysis and Transwell chamber assay, respectively. The potential target gene of miR466 was predicted using bioinformatic analysis, which was further confirmed by luciferase reporter assay, RTqPCR and western blot analysis. It was found that miR466 was obviously decreased in HCC tissues and cell lines. The results of functional experiments revealed that restoration of miR466 expression suppressed the proliferation, induced apoptosis, and reduced the metastasis of HCC cells. In addition, metadherin (MTDH) was identified as a direct target of miR466 in HCC cells. Furthermore, MTDH was upregulated in HCC tissues, which was inversely correlated with the miR466 level. Moreover, inhibition of MTDH displayed similar tumorsuppressing roles as miR466 upregulation in HCC cells. In addition, MTDH reintroduction restored the tumorsuppressor activity of miR466 overexpression in HCC cells. These findings suggest that miR466 is a potential therapeutic tool for HCC therapy.
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Carcinoma Hepatocelular/genética , Moléculas de Adhesión Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , Anciano , Apoptosis/genética , Carcinoma Hepatocelular/patología , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Biología Computacional , Regulación hacia Abajo , Femenino , Genes Supresores de Tumor , Humanos , Hígado/patología , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana , MicroARNs/antagonistas & inhibidores , Persona de Mediana Edad , Proteínas de Unión al ARN , Regulación hacia ArribaRESUMEN
The spatial and temporal Ag distribution determines the subsequent T cell and B cell activation at the distinct anatomical locations in the lymph node (LN). It is well known that LN conduits facilitate small Ag distribution in the LN, but the mechanism of how Ags travel along LN conduits remains poorly understood. In C57BL/6J mice, using FITC as a fluorescent tracer to study lymph distribution in the LN, we found that FITC preferentially colocalized with LN capsule-associated (LNC) conduits. Images generated using a transmission electron microscope showed that LNC conduits are composed of solid collagen fibers and are wrapped with fibroblastic cells. Superresolution images revealed that high-intensity FITC is typically colocalized with elastin fibers inside the LNC conduits. Whereas tetramethylrhodamine isothiocyanate appears to enter LNC conduits as effectively as FITC, fluorescently-labeled Alexa-555-conjugated OVA labels significantly fewer LNC conduits. Importantly, injection of Alexa-555-conjugated OVA with LPS substantially increases OVA distribution along elastin fibers in LNC conduits, indicating immune stimulation is required for effective OVA traveling along elastin in LN conduits. Finally, elastin fibers preferentially surround lymphatic vessels in the skin and likely guide fluid flow to the lymphatic vessels. Our studies demonstrate that fluid or small molecules are preferentially colocalized with elastin fibers. Although the exact mechanism of how elastin fibers regulate Ag trafficking remains to be explored, our results suggest that elastin can be a potentially new target to direct Ag distribution in the LN during vaccine design.
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Elastina/ultraestructura , Ganglios Linfáticos/ultraestructura , Animales , Elastina/metabolismo , Femenino , Linfa/metabolismo , Ganglios Linfáticos/metabolismo , Vasos Linfáticos/metabolismo , Vasos Linfáticos/ultraestructura , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Ovalbúmina/metabolismoRESUMEN
The purpose of this study was to investigate the protective effect of catalpol on Lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced acute liver injury in mice. The mouse model was established by injection of LPS and D-gal. Catalpol (2.5, 5, 10 mg/kg) were pretreated intraperitoneally 1 h before LPS and D-gal. The survival rate, AST, ALT, MDA, MPO activity, hepatic tissue histology, TNF-α level, and NF-κB activation were assayed. The results revealed that catalpol dose-dependently elevated the survival rate. Furthermore, catalpol reduced the activities of AST, ALT, MDA, and MPO. The production of TNF-α was also inhibited by treatment of catalpol. In addition, catalpol inhibited LPS/D-gal-induced NF-κB activation. The expression of Nrf2 and HO-1 were up-regulated by treatment of catalpol. These results indicated that pretreatment with catalpol could attenuate LPS/D-gal-induced acute liver injury in mice and the underlying mechanism may due to the inhibition of NF-κB signaling pathway and the activation of Nrf2 signaling pathway.
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Colorectal cancer (CRC) remains a primary contributor to cancerassociated mortality. The Lin28/let7 axis has previously been verified to participate in numerous pathophysiological processes involved in CRC. However, the potential roles and underlying mechanisms of this axis in apoptosis during CRC remain to be fully elucidated. The present study aimed to evaluate the role and reveal the molecular mechanisms of the Lin28/let7 axis in the apoptosis of CRC cells. An MTT assay was conducted to assess the cell viability of HCT116 and HT29 CRC cells, and caspase3 activity was analyzed to measure the apoptosis of CRC cells. Western blotting and reverse transcriptionquantitative polymerase chain reaction were performed to examine the expression of Lin28, Bcell lymphoma 2 (Bcl2), Bcl2associated X protein, Bcl2like 1 (BCL2L1) and let7c. The present study demonstrated that Lin28 was upregulated whereas let7c was downregulated in CRC tissues and cell lines compared with normal tissues and NCM460 normal colon epithelial cells, respectively. Forced overexpression of let7c promoted apoptosis in CRC cells, which was at least partially mediated via the targeting of BCL2L1. Furthermore, knockdown of Lin28 decreased viability and promoted apoptosis in CRC cells, whereas this effect was attenuated by let7c inhibition. The findings of the present study suggest the involvement of the Lin28/let7c axis in apoptosis during CRC, and indicate the potential role of this pathway as a novel therapeutic target in CRC.
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Apoptosis/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , MicroARNs/genética , Proteínas de Unión al ARN/genética , Proteína bcl-X/genética , Adulto , Anciano , Caspasa 3/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procesamiento Postranscripcional del ARN , Regulación hacia ArribaRESUMEN
AIM: To investigate whether heat shock pretreatment (HSP) improves mesenchymal stem cell (MSC) repair via autophagy following hepatic ischemia-reperfusion injury (HIRI). METHODS: Apoptosis of MSCs was induced by 250 mM hydrogen peroxide (H2O2) for 6 h. HSP was carried out using a 42â °C water bath for 1, 2 or 3 h. Apoptosis of MSCs was analyzed by flow cytometry, and Western blot was used to detect Bcl-2, Bax and cytochrome C expression. Autophagy of MSCs was analyzed by flow cytometry and transmission electron microscopy, and the expression of beclin I and LC3-II was detected by Western blot. MSCs were labeled in vivo with the fluorescent dye, CM-Dil, and subsequently transplanted into the portal veins of rats that had undergone HIRI. Liver levels of proliferating cell nuclear antigen (PCNA) were quantified by fluorescent microscopy. Serum aminotransferase activity and the extent of HIRI were also assessed at each time point. RESULTS: HSP for 2 h reduced apoptosis of MSCs induced by H2O2 as seen by a decrease in apoptotic rate, a decrease in Bax and cytochrome C expression and an increase in Bcl-2 expression (P < 0.001). In addition, HSP for 2 h induced autophagy of MSCs exposed to H2O2 as shown by an increase in acidic vesicular organelle-positive cells, beclin 1 and LC3-II expression, and autophagosome formation (P < 0.05). Treatment with 3-methyladenine attenuated HSP-induced autophagy and abolished the protective effects of HSP on the apoptosis of MSCs. Rapamycin failed to have additional effects on either autophagy or apoptosis compared with HSP alone. The phosphorylation of p38MAPK was significantly elevated and the phosphorylation of mTOR was downregulated in heat shock pretreated MSCs. Treatment with the p38MAPK inhibitor, SB203580, reduced HSP-induced autophagy in MSCs. In vivo studies showed that the transplantation of HSP-MSCs resulted in lower serum aminotransferase levels, lower Suzuki scores, improved histopathology and an increase in PCNA-positive cells (P < 0.05). CONCLUSION: HSP effectively induces autophagy following exposure to H2O2 via the p38MAPK/mTOR pathway, which leads to enhanced MSC survival and improved MSC repair following HIRI in rats.
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Autofagia , Respuesta al Choque Térmico , Calor , Hepatopatías/cirugía , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/ultraestructura , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/efectos de los fármacos , Beclina-1 , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Citometría de Flujo , Peróxido de Hidrógeno/toxicidad , Hepatopatías/metabolismo , Hepatopatías/patología , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Microscopía Electrónica de Transmisión , Proteínas Asociadas a Microtúbulos/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC. METHODS: miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target. RESULTS: miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro. CONCLUSIONS: Taken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC.
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Neoplasias de los Conductos Biliares/metabolismo , Colangiocarcinoma/metabolismo , Transición Epitelial-Mesenquimal/genética , MicroARNs/metabolismo , Proteína Smad4/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Neoplasias de los Conductos Biliares/genética , Línea Celular Tumoral , Colangiocarcinoma/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , MicroARNs/genética , Persona de Mediana Edad , Transducción de Señal , Proteína Smad4/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide. miRNAs have been suggested to have important roles in HCC development. The purpose of this study was to determine the role of miR-139-5p in regulation of epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Expression levels of miR-139-5p in 49 HCC specimens with adjacent tissues and five HCC cell lines were assessed by quantitative RT-PCR. We found that miR-139-5p was down-regulated in 89.7% of the HCC tissue samples and all of the HCC cell lines. In addition, luciferase reporter assays validated direct binding of miR-139-5p to the 3' untranslated region of zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. Ectopic expression of miR-139-5p suppressed and miR-139-in promoted EMT, migration, and invasion in Hep3B and SMMC7721 cells. Furthermore, over-expression of ZEB1 and ZEB2 ablated the inhibitory effects of miR-139-5p on migration and invasion in HCC cells. Our study indicates that miR-139-5p functions as a suppressor of HCC EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic HCC.
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Carcinoma Hepatocelular/genética , Transición Epitelial-Mesenquimal , Proteínas de Homeodominio/genética , Neoplasias Hepáticas/genética , Hígado/patología , MicroARNs/genética , Proteínas Represoras/genética , Factores de Transcripción/genética , Regiones no Traducidas 3' , Secuencia de Bases , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/metabolismo , Datos de Secuencia Molecular , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
Large clival meningiomas are a major surgical challenge with risks to life and permanent deficit. A 65-year-old man with a meningioma anterior to the medulla oblongata with brain stem compression was operated with far-lateral approach assisted by multimodal neuronavigation and neurophysiological monitoring techniques. Total resection of the tumor was achieved with no intra- or post-operative complications. This case illustrates the benefits obtained by a multimodal approach.
Asunto(s)
Neoplasias del Tronco Encefálico/cirugía , Ángulo Pontocerebeloso/cirugía , Monitorización Neurofisiológica Intraoperatoria/métodos , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Neuronavegación/métodos , Anciano , Humanos , MasculinoRESUMEN
The aim of the present study was to determine the effect of downregulating the expression of glucose-regulated protein 78 (Grp78) and Grp94 upon the rate of proliferation and apoptosis in the human gastric cancer SGC-7901 cell line. The SGC-7901 cells were divided into three groups as follows: i) An experimental group co-transfected with the small interfering RNA vectors, psiSTRIKE™/Grp78 and psiSTRIKE/Grp94; ii) a negative control group, in which only Lipofectamine 2000™ was used to transfect the cells; and iii) a blank control group, in which cells were left untouched and not transfected with any agent. The transcriptional expression of Grp78 and Grp94 was assayed by reverse transcription polymerase chain reaction, and the protein expression of Grp78 and Grp94 was determined using an immunofluorescence assay at 24, 48 and 72 h post-transfection. The rates of cellular proliferation and apoptosis were assayed using MTT and flow cytometry analyses, respectively. The mRNA and protein expression of Grp78 and Grp94 in the gastric cancer cells was downregulated at 72 h post-transfection. In addition, the results of the MTT assay revealed that the proliferation rate of the gastric cancer cells in the co-transfected group was significantly inhibited at 72 h post-transfection compared with the control groups (P<0.05). The apoptosis ratio was significantly increased in the experimental group compared with the control groups (P<0.05). The co-transfection of the SGC-7901 cells with psiSTRIKE/Grp78 and psiSTRIKE/Grp94 markedly reduced the expression of Grp78 and Grp94, respectively. Furthermore, the reduction in the expression of Grp78 and Grp94 inhibited cellular proliferation and significantly downregulated the rate of apoptosis in the SGC-7901 cells in vitro.
RESUMEN
BACKGROUND AND AIMS: The information about clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients is limited. We performed this study to assess the impact of age on potential differences in clinical characteristics, treatment patterns and outcome in HCC patients. METHODS: Clinical data of 164 "elderly" (≥70 years old) and 531 "younger" (<70 years old) HCC patients treated at a Chinese tertiary university-affiliated medical center between April 2004 and April 2012 were collected and compared using various parameters. RESULTS: Compared with younger patients, the elderly patients had a higher proportion of females (32.9 % vs. 18.1 %, p < 0.001), less hepatitis B virus (HBV) infection (40.9 % vs. 76.6 %, p < 0.001), more hepatitis C virus (HCV) infection (23.8 % vs. 5.6 %, p < 0.001), less liver cirrhosis (68.3 % vs. 76.8 %, p = 0.03) and massive tumors (12.8 % vs. 21.8 %, p = 0.01). There was no significant difference between the two groups in Child-Pugh class and tumor stages. The elderly patients received less surgical resection (14.6 % vs. 29.6 %, p < 0.001) and more supportive care (48.8 % vs. 37.9 %, p = 0.01) than younger patients. The overall survival was not significantly different between the two groups (26.2 mo. vs. 28.3 mo., p = 0.75). CONCLUSION: Characteristics that distinguish elderly from younger HCC patients included more female, less HBV infection, more HCV infection, less liver cirrhosis and massive tumors. Significant differences were observed in therapeutic strategies utilized with the two groups, but the overall survival was not significantly different.