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We investigated the effects of transcriptional intermediary factor 1γ (TIF1γ) and SMAD4 on the proliferation and liver metastasis of colorectal cancer (CRC) cells through knockdown of TIF1γ and/or SMAD4 and knockdown of TIF1γ and/or restoration of SMAD4 expression. Furthermore, we examined TIF1γ and SMAD4 expression in human primary CRC and corresponding liver metastatic CRC specimens. TIF1γ promoted but SMAD4 inhibited the proliferation of CRC cells by competitively binding to activated SMAD2/SMAD3 complexes and then reversely regulating c-Myc, p21, p27, and cyclinA2 levels. Surprisingly, both TIF1γ and SMAD4 reduced the liver metastasis of all studied CRC cell lines via inhibition of MEK/ERK pathway-mediated COX-2, Nm23, uPA, and MMP9 expression. In patients with advanced CRC, reduced TIF1γ or SMAD4 expression was correlated with increased invasion and liver metastasis and was a significant, independent risk factor for recurrence and survival after radical resection. Patients with advanced CRC with reduced TIF1γ or SAMD4 expression had higher recurrence rates and shorter overall survival. TIF1γ and SMAD4 competitively exert contrasting effects on cell proliferation but act complementarily to suppress the liver metastasis of CRC via MEK/ERK pathway inhibition. Thus, reduced TIF1γ or SMAD4 expression in advanced CRC predicts earlier liver metastasis and poor prognosis.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteína Smad4 , Factores de Transcripción/metabolismoRESUMEN
Endothelial cell dysfunction is the main pathology of atherosclerosis (AS). Sirtuin 6 (SIRT6), a deacetylase, is involved in AS progression. This study aimed to investigate the impacts of SIRT6 on the pyroptosis of endothelial cells and its underlying mechanisms. ApoE-/- mice were fed a high-fat diet (HFD) to establish the AS mouse model, atherosclerotic lesions were evaluated using oil red O staining, and blood lipids and inflammatory factors were measured using corresponding kits. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the cell model, and pyroptosis was evaluated by flow cytometry, ELISA, and western blot. Immunoprecipitation (IP), co-IP, western blot, and immunofluorescence were used to detect the molecular mechanisms. The results showed that SIRT6 expression was downregulated in the blood of HFD-induced mice and ox-LDL-induced HUVECs. Overexpression of SIRT6 reduced atherosclerotic lesions, blood lipids, and inflammation in vivo and suppressed pyroptosis of HUVECs in vitro. Moreover, SIRT6 interacted with ASC to inhibit the acetylation of ASC, thus, reducing the interaction between ASC and NLRP3. Moreover, SIRT6 inhibits endothelial cell pyroptosis in the aortic roots of mice by deacetylating ASC. In conclusion, SIRT6 deacetylated ASC to inhibit its interaction with NLRP3 and then suppressed pyroptosis of endothelial cells, thus, decelerating the progression of AS. The findings provide new insights into the function of SIRT6 in AS.
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Aterosclerosis , Células Endoteliales de la Vena Umbilical Humana , Lipoproteínas LDL , Piroptosis , Sirtuinas , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Sirtuinas/metabolismo , Ratones , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Proteínas Adaptadoras de Señalización CARD/metabolismo , Modelos Animales de Enfermedad , Dieta Alta en Grasa , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: This study aimed to identify the biological functions, expression modes, and possible mechanisms underlying the relationship between metastatic human hepatocellular carcinoma (HCC) and MicroRNA-188-5p (miR-188) dysregulation using cell lines. METHODS: A decrease in miR-188 was detected in low and high metastatic HCC cells compared to that in normal hepatic cells and non-invasive cell lines. Gain- and loss-of-function experiments were performed in vitro to investigate the role of miR-188 in cancer cell (Hep3B, HepG2, HLF, and LM3) proliferation and migration. RESULTS: miR-188 mimic transfection inhibited the proliferation of metastatic HLF and LM3 cells but not non-invasive HepG2 and Hep3B cells; nonetheless, miR-188 suppression promoted the growth of HLF and LM3 cells. miR-188 upregulation inhibited the migratory rate and invasive capacity of HLF and LM3, rather than HepG2 and Hep3B cells, whereas transfection of a miR-188 inhibitor in HLF and LM3 cells had the opposite effects. Dual-luciferase reporter assays and bioinformatics prediction confirmed that miR-188 could directly target forkhead box N2 (FOXN2) in HLF and LM3 cells. Transfection of miR-188 mimics reduced FOXN2 levels, whereas miR-188 inhibition resulted in the opposite result, in HLF and LM3 cells. Overexpression of FOXN2 in HLF and LM3 cells abrogated miR-188 mimic-induced downregulation of proliferation, migration, and invasion. In addition, we found that miR-188 upregulation impaired tumor growth in vivo. CONCLUSIONS: In summary, this study showed thatmiR-188 inhibits the proliferation and migration of metastatic HCC cells by targeting FOXN2.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismoRESUMEN
Early screening and diagnosis of cervical precancerous lesions are very important to prevent cervical cancer. High-quality colposcopy images will help doctors make faster and more accurate diagnoses. To tackle the problem of low image quality caused by complex interference during colposcopy operation, this paper proposed a conditional entropy generative adversarial networks framework for image enhancement. A decomposition network based on Retinex theory is constructed to obtain the reflection images of the low-quality images, then the conditional generative adversarial network is used as the enhancement network. The low-quality images and the decomposed reflection images are both input the enhancement network for training, and the conditional entropy distance is used as a part of the loss of the conditional generative adversarial network to alleviate the over-fitting problem during the training process. The test results show that compared with published methods, the proposed method of this paper can significantly improve the image quality, and can enhance the colposcopy image while retaining image details.
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Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Entropía , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Type 2 diabetes mellitus (T2DM) is one of the major public health problems worldwide; both genetic and environmental factors are its risk factors. Arsenic, an environmental pollutant, might be a risk factor for T2DM, but the association of low-to-moderate level arsenic exposure with the risk of T2DM is still inconsistent. Single nucleotide polymorphisms (SNPs) can affect the development of T2DM, but the study on KEAP1 rs11545829 (G>A) SNP is few. In this paper, we explored the effect of KEAP1 rs11545829 (G>A) SNP and low-to-moderate level arsenic exposure on risk of T2DM in a cross-sectional case-control study conducted in Shanxi, China. Total of 938 participants, including 318 T2DM cases and 618 controls, were enrolled. Blood glycosylated haemoglobin (HbA1c) was detected by Automatic Biochemical Analyzer, and participants with HbA1câ§6.5% were diagnosed as T2DM. Urinary total arsenic (tAs, mg/L), as the indicator of arsenic exposure, was detected by liquid chromatography-atomic fluorescence spectrometry (LC-AFS). Genomic DNA was extracted and the genotypes of KEAP1 rs11545829 SNP were examined by multiplex polymerase chain reaction (PCR). The urinary tAs concentration in recruited participants was 0.075 (0.03-0.15) mg/L, and was associated with an increased risk of T2DM (OR = 8.45, 95% CI 2.63-27.17); rs11545829 mutation homozygote AA genotype had a protective effect on risk of T2DM (OR = 0.42, 95 % CI 0.25-0.73). Although this protective effect of AA genotype was found in participants with higher urinary tAs level (>0.032 mg/L) (OR = 0.48, 95% CI 0.26-0.86), there was no interaction effect for arsenic exposure and rs11545829 SNP on risk of T2DM. In addition, BMI modified the association between rs11545829 SNP and the risk of T2DM (RERI = -1.11, 95% CI -2.18-0.04). The present study suggest that low-to-moderate level arsenic exposure may be a risk factor, while KEAP1 rs11545829 SNP mutation homozygote AA genotype may be a protective factor for risk of T2DM, especially for T2DM patients with urinary tAs level>0.032 mg/L.
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Arsénico , Diabetes Mellitus Tipo 2 , Proteína 1 Asociada A ECH Tipo Kelch , Arsénico/toxicidad , Arsénico/orina , Estudios de Casos y Controles , China/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVES: To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with pilocarpine. MATERIALS AND METHODS: In situ irradiation models of SMGs in Wistar rats were conducted, and the glands were exposed to X-radiation at a single dose of 20 Gy. Pilocarpine was intraperitoneally injected 60 min prior to radiation and continuous 6 days postirradiation for a total of 7 days. Salivary secretion, histological changes, pro-inflammatory cytokines, alterations in tight junctions (TJs), and functional membrane proteins aquaporin-5 (AQP5) and claudin-4 mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks after irradiation. RESULTS: Salivary secretion of the irradiated glands was reduced at 1 and 12 weeks. As well, acinar cell numbers, TJ width, and the levels of M3 receptor and AQP5 were decreased. In contrast, tumor necrosis factor-α, interleukin 6, interleukin 1α, and the expression of the TJ protein claudin-4 were significantly increased in irradiated SMGs. Notably, all the alterations were attenuated by pilocarpine treatment. CONCLUSIONS: Pilocarpine could improve the secretory function of irradiated rat SMGs via reducing inflammation, ameliorating the structural injury of TJs, and attenuating the up-regulation of claudin-4 expression.
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Pilocarpina , Glándula Submandibular , Animales , Claudina-4/metabolismo , Claudinas/metabolismo , Claudinas/farmacología , Pilocarpina/farmacología , Ratas , Ratas Wistar , Uniones Estrechas/metabolismoRESUMEN
A disease outbreak occurred in Murray cod Maccullochella peelii peelii in a recirculating aquaculture farm in Tianjin city, China, in 2019. Strain MRX-2019 was isolated and considered to be the etiological pathogen; it was identified as Flavobacterium columnare based on a 16S rDNA gene sequence analysis and physiological and biochemical tests. The effect of salinity on the growth of MRX-2019 was investigated in vitro. Salinity >4 (i.e. 6) inhibited MRX-2019 growth, whereas 8 and 10 salinity killed it. The effect of 4 salinity on F. columnare was not significant (p > 0.05). When MRX-2019-infected Murray cod were treated with 4, 6, or 8 salinity, the mortality rate was reduced by 8.9, 67.76, or 75.56%, respectively, compared with that of the control. However, the mortality rate increased by 7.77% at 10 salinity. In this study, we found that maintaining the fish in freshwater with 6-8 salinity effectively reduced the mortality of these fish when infected with F. columnare. The findings provide an environmentally friendly control strategy for columnaris disease in Murray cod.
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Inmersión , Perciformes , Animales , Flavobacterium , Cloruro de SodioRESUMEN
OBJECTIVE: In the present study, we intend to assess the function of Sema3A in osteointegration of titanium implants both in vivo and in vitro. MATERIAL AND METHODS: Briefly, Sema3A was transfected in HBMSCs cells to detect its effect on osteogenesis. Subsequently, an in vivo rabbit model was established. Eighteen female rabbits were randomly assigned into three groups (n=6), and rabbits in the two treatment groups (OVX groups) were subjected to bilateral ovariectomy, while those in the control group were treated with sham operation. Twelve weeks later, we first examined expression levels of Sema3A in rabbits of the three groups. Titanium implants were implanted in rabbit proximal tibia. Specifically, rabbits in sham group were implanted with Matrigel, while the remaining in the OVX experimental group (OVX+Sema3A group) and OVX group were implanted with Matrigel containing Sema3A adeno-associated virus or empty vector, respectively. RESULTS: Histomorphometry results uncovered that rabbits in the OVX+Sema3A group had a significantly higher BIC compared with those of the OVX group on the 12th week of post-implantation. And compared with the OVX group, the maximum push-out force increased by 89.4%, and the stiffness increased by 39.4%, the toughness increased by 63.8% in the OVX+Sema3A group at 12 weeks. CONCLUSION: Sema3A has a positive effect on promoting early osseointegration of titanium implants in osteoporotic rabbits. CLINICAL RELEVANCE: Our research found that Sema3A can improve the osteogenic ability of bone marrow stem cells and promotes osseointegration during osteoporosis.
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Implantes Dentales , Osteoporosis , Animales , Femenino , Conejos , Oseointegración , Osteoporosis/cirugía , Ovariectomía , Tibia , TitanioRESUMEN
OBJECTIVE: This study aimed to investigate the quality of life (QOL) of patients with cleft lip and palate and velopharyngeal insufficiency (VPI) in relation to sex, age, age at initial cleft lip surgery, and age at initial cleft palate surgery. DESIGN: This is a cross-sectional study. SETTING: The study was conducted in a tertiary medical center. PARTICIPANTS: The participants were caregivers of 72 patients with cleft lip and palate and VPI aged 4 to 20 years. MAIN OUTCOME MEASURE(S): Participants completed the Chinese version of the caregiver report of the VPI Effects on Life Outcomes (VELO) questionnaire. The Mann-Whitney U test was used to evaluate the patients' sex, age, age at initial cleft lip repair, and age at initial cleft palate repair in relation to VELO total score and domains. Spearman correlation analysis was completed including all study variables. Associations between the study variables and the VELO total score were tested using a generalized linear mixed model. RESULTS: In the univariate analysis, patients' age and age at initial cleft palate surgery influenced the QOL of patients with VPI. There were no differences in the VELO total score or domains based on sex or age at first cleft lip surgery. In the generalized linear mixed model, patients older than 8 years had higher VELO total scores. CONCLUSIONS: By caregiver report, the QOL of patients under age 8 years with VPI was lower than older patients. In addition, the caregiver impact domain was higher for parents of children who had their initial cleft palate surgery at age 2 years or younger.
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Labio Leporino , Fisura del Paladar , Insuficiencia Velofaríngea , Niño , Preescolar , China , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Estudios Transversales , Humanos , Calidad de Vida , Resultado del Tratamiento , Insuficiencia Velofaríngea/cirugíaRESUMEN
Pressure processing is efficient to regulate the structural and physical properties of two-dimensional (2D) halide perovskites which have been emerging for advanced photovoltaic and light-emitting applications. Increasing numbers of studies have reported pressure-induced and/or enhanced emission properties in the 2D halide perovskites. However, no research has focused on their photoresponse properties under pressure tuning. It is also unclear how structural change affects their excitonic features, which govern the optoelectronic properties of the halide perovskites. Herein, we report significantly enhanced photocurrents in the all-inorganic 2D perovskite Cs2PbI2Cl2, achieving over 3 orders of magnitude increase at the industrially achievable level of 2 GPa in comparison with its initial photocurrent. Lattice compression effectively regulates the excitonic features of Cs2PbI2Cl2, reducing the exciton binding energy considerably from 133 meV at ambient conditions to 78 meV at 2.1 GPa. Impressively, such a reduced exciton binding energy of 2D Cs2PbI2Cl2 is comparable to the values of typical 3D perovskites (MAPbBr3 and MAPbI3), facilitating the dissociating of excitons into free carriers and enhancing the photocurrent. Further pressurization leads to a layer-sliding-induced phase transition and an anomalous negative linear compression, which has not been observed so far in other halide perovskites. Our findings reveal the dramatically enhanced photocurrents in the 2D halide perovskite by regulating its excitonic features and, more broadly, provide new insights into materials design toward extraordinary properties.
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To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20 Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12 weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.
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Precondicionamiento Isquémico , Glándula Submandibular , Animales , Ratas , Ratas Wistar , Receptor Muscarínico M3 , SalivaciónRESUMEN
PURPOSE: This prospectively designed study aimed to investigate the association between sleep duration and overweight in a cohort of Chinese adolescents. METHODS: A school-based cohort study with a 2-year follow-up was conducted among Chinese adolescents in Ningbo region (China). For the baseline study, 1901 school-aged Chinese children aged 12-13 years were recruited. Finally, 1510 adolescents were successfully reinterviewed in October 2018. Participants were asked to complete a self-administered questionnaire, and their heights and weights were directly measured. RESULTS: Overweight adolescents had shorter sleep duration or later bedtimes than non-overweight children in baseline (P < 0.05). In the multivariable linear regression analysis, sleep duration was marginally significantly correlated with body mass index (BMI) at baseline and significantly correlated with this parameter at a 2-year follow-up (ß = - 0.23, 95% confidence interval (CI): - 0.51 to 0.04, P < 0.1; ß = - 0.27, 95% CI: - 0.42 to - 0.11, P < 0.05, respectively). After adjusting for potential confounders, the multivariable logistic regression analysis revealed associations of a longer sleep duration at baseline with a reduced likelihood of participants being overweight both at baseline and at follow-up (adjusted odds ratio (AOR) = 0.81, 95% CI: 0.66 to 1.00, P = 0.05; AOR = 0.43, 95% CI:0.24 to 0.76, P < 0.05, respectively). CONCLUSIONS: Shorter sleep was associated with an increased likelihood of being overweight in Chinese adolescents, while a 1-h decrease in sleep per night led to a more than 50% increase in the overweight risk at the 2-year follow-up.
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Sobrepeso/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Adolescente , Índice de Masa Corporal , Niño , China , Estudios de Cohortes , Correlación de Datos , Femenino , Estudios de Seguimiento , Humanos , Funciones de Verosimilitud , Estudios Longitudinales , Masculino , Sobrepeso/diagnóstico , Estudios Prospectivos , Factores de Riesgo , Sueño , Trastornos del Sueño-Vigilia/diagnóstico , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
To systematically review the efficacy and safety of Zhibitai Capsules combined with chemical drugs versus chemical drugs alone in regulating blood lipid of patients of coronary heart disease, so as to provide evidence-based reference for clinical treatment. In this study, PubMed, EMbase, Cochrane Library, China Knowledge Network Database(CNKI), Technology Journal Database(VIP) and WanFang Database(WanFang) were retrieved to find the randomized controlled trials(RCT) about therapeutic efficacy of Zhibitai Capsules combined with statins(experimental group)versus statins alone(control group)in the treatment of regulating blood lipid of patients with coronary heart disease. The retrieval time was restricted to be from the inception to October 2019. The data were extracted from the randomized controlled trials. Meta-analysis was conducted by RevMan 5.3 statistical software after quality evaluation by Cochrane 5.1.0 quality evaluation tool(blood lipid level, inflammation indicators, traditional Chinese medicine syndrome score and adverse reactions). A total of 11 RCT were included, involving 1 538 patients. The results of Meta-analysis showed that in terms of decrease of total cholesterol(MD=-0.15,95%CI[-0.25,-0.05],P=0.004), decrease of triglycerides improvement(MD=-0.16,95%CI[-0.23,-0.10],P<0.000 01), decrease of low-density lipoprotein(MD=-0.08,95%CI[-0.15,-0.01],P=0.03), and increase of high-density lipoprotein(MD=0.06,95%CI[0.03,0.10],P=0.000 2), experimental group was better than control group. At the same time, the incidence of adverse reactions were low in the experimental group(OR=0.40,95%CI[0.18,0.85],P=0.02). As a result, in treatment of coronary heart disease, the therapeutic efficacy of Zhibitai Capsules combined with statins is better than statins alone in lowering total cholesterol level, triglyceride level, low-density lipoprotein level, and increasing high-density lipoprotein level. Patients in the experimental group had a low incidence of adverse events, but the heterogeneity was slightly higher, and the result had a poor stability. However, due to the small sample size of studies included, some experimental designs were not perfect, which reduces the recommendation level and evidence intensity of this system evaluation. Therefore, high-quality multi-center, large-sample, randomized, double-blind randomized controlled trials are needed for providing more reliable basis.
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Enfermedad Coronaria , Medicamentos Herbarios Chinos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Cápsulas , China , Humanos , LípidosRESUMEN
BACKGROUND: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. METHODS: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. RESULTS: Eighty nine TACE procedures (1.35 ± 0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), "typical tumor enhancement" (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. CONCLUSIONS: The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.
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Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Hígado/diagnóstico por imagen , Adulto , Anciano , Arterias/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Femenino , Humanos , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Necrosis , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND To determine whether the levels of b2-glycoprotein I (b2-GPI)/oxidized low-density lipoprotein (oxLDL) complexes are correlated with cerebral infarction in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The levels of ß2-GPI/oxLDL complexes, oxLDL, routine lipid/lipoprotein parameters, oxidative stress molecules, and inflammatory factors were measured in 78 healthy controls, 82 diabetics without cerebral infarction, and 79 diabetics with cerebral infarction. Correlation, multiple linear regression, and logistic regression analyses were performed. RESULTS Serum ß2-GPI/oxLDL complexes and oxLDL levels were significantly elevated in cerebral infarction in patients with T2DM (ß2-GPI/oxLDL: 1.09±0.16 U/mL; oxLDL: 47.83±8.17 mmol/L) compared with T2DM without cerebral infarction (b2-GPI/oxLDL: 0.95±0.13 U/mL; oxLDL: 41.24±7.12 mmol/L) and healthy controls (ß2-GPI/oxLDL: 0.81±0.12 U/mL; oxLDL: 27.97±4.57 mmol/L). The levels of ß2-GPI/oxLDL complex in lacunar infarction (1.16±0.15 U/ml) were significantly higher than atherothrombotic infarction (1.07±0.19 U/ml) and cardioembolic infarction (1.00±0.23 U/ml). In all patients with T2DM, the ß2-GPI/oxLDL levels were positively correlated with total cholesterol (r=0.474, p=0.001) and triglycerides (r=0.431, p=0.003). oxLDL levels were positively correlated with total cholesterol (r=0.445, p=0.002). The logistic regression analysis indicated that elevated b2-GPI/oxLDL and oxLDL levels were independently associated with diabetic cerebral infarction. CONCLUSIONS Elevated levels of serum b2-GPI/oxLDL complexes are associated with cerebral infarction in patients with T2DM, especially in those with lacunar infarction.
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Infarto Cerebral/sangre , Diabetes Mellitus Tipo 2/sangre , Lipoproteínas LDL/sangre , beta 2 Glicoproteína I/sangre , Estudios de Casos y Controles , Infarto Cerebral/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Inflamación/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estrés OxidativoRESUMEN
For Industrial Wireless Sensor Networks (IWSNs), sending data with timely style to the stink (or control center, CC) that is monitored by sensor nodes is a challenging issue. However, in order to save energy, wireless sensor networks based on a duty cycle are widely used in the industrial field, which can bring great delay to data transmission. We observe that if the duty cycle of a small number of nodes in the network is set to 1, the sleep delay caused by the duty cycle can be effectively reduced. Thus, in this paper, a novel Portion of Nodes with Larger Duty Cycle (PNLDC) scheme is proposed to reduce delay and optimize energy efficiency for IWSNs. In the PNLDC scheme, a portion of nodes are selected to set their duty cycle to 1, and the proportion of nodes with the duty cycle of 1 is determined according to the energy abundance of the area in which the node is located. The more the residual energy in the region, the greater the proportion of the selected nodes. Because there are a certain proportion of nodes with the duty cycle of 1 in the network, the PNLDC scheme can effectively reduce delay in IWSNs. The performance analysis and experimental results show that the proposed scheme significantly reduces the delay for forwarding data by 8.9~26.4% and delay for detection by 2.1~24.6% without reducing the network lifetime when compared with the fixed duty cycle method. Meanwhile, compared with the dynamic duty cycle strategy, the proposed scheme has certain advantages in terms of energy utilization and delay reduction.
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BACKGROUND: We aimed to investigate the correlations between ACE2 polymorphisms and type 2 diabetes mellitus (T2DM) combined with cerebral stroke (CS). METHODS: A total of 346 patients treated or hospitalized in our hospital were enrolled, including 181 cases without cerebrovascular complications (T2DM group) and 165 cases combined with CS (T2DM + CS group); 284 healthy individuals were selected as the control group. PCR-RFLP and ELISA were used to analyze ACE2 G8790A polymorphisms and serum ACE2 levels, respectively. RESULTS: Significant differences were observed in the genotype/allele frequency of ACE2 G8790A between the T2DM + CS and control groups, and the T2DM and T2DM + CS groups, and in the genotype frequency of ACE2 G8790A between the T2DM and the control groups. The A allele may increase the risk of T2DM combined with CS. The AA genotype may also increase the risk of T2DM combined with CS (OR = 3.733, 95%CI = 2.069-6.738; OR = 3.597, 95%CI = 1.884-6.867). Serum ACE2 levels showed statistically significant differences among the groups. Systolic pressure and diastolic pressure were protective factors of T2DM combined with CS. CONCLUSION: The ACE2 G8790A polymorphism in T2DM patients was correlated with CS, and the A allele might be a risk factor of T2DM combined with CS.
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Diabetes Mellitus Tipo 2/genética , Peptidil-Dipeptidasa A/sangre , Peptidil-Dipeptidasa A/genética , Polimorfismo de Nucleótido Simple/genética , Accidente Cerebrovascular/genética , Enzima Convertidora de Angiotensina 2 , Presión Sanguínea , Diabetes Mellitus Tipo 2/sangre , Ensayo de Inmunoadsorción Enzimática , Frecuencia de los Genes/genética , Genotipo , Humanos , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Accidente Cerebrovascular/sangreRESUMEN
UNLABELLED: Transcriptional intermediary factor 1 gamma (TIF1γ) may play either a potential tumor-suppressor or -promoter role in cancer. Here we report on a critical role of TIF1γ in the progression of hepatocellular carcinoma (HCC). Reduced expression of TIF1γ was detected in HCC, especially in advanced HCC tissues, compared to adjacent noncancerous tissues. HCC patients with low TIF1γ expression had shorter overall survival times and higher recurrence rates than those with high TIF1γ expression. Reduced TIF1γ expression was an independent and significant risk factor for recurrence and survival after curative resection. In HCC cells, TIF1γ played a dual role: It promoted tumor growth in early-stage HCC, but not in advanced-stage HCC, whereas it inhibited invasion and metastasis in both early- and advanced-stage HCC. Mechanistically, we confirmed that TIF1γ inhibited transforming growth factor-ß/ Drosophila mothers against decapentaplegic protein (TGF-ß/Smad) signaling through monoubiquitination of Smad4 and suppressed the formation of Smad2/3/4 complex in HCC cells. TGF-ß-inducing cytostasis and metastasis were both inhibited by TIF1γ in HCC. We further proved that TIF1γ suppressed cyotstasis-related TGF-ß/Smad downstream c-myc down-regulation, as well as p21/cip1 and p15/ink4b up-regulation in early-stage HCC. Meanwhile, TGF-ß inducible epithelial-mesenchymal transition and TGF-ß/Smad downstream metastatic cascades, including phosphatase and tensin homolog deleted on chromosome ten down-regulation, chemokine (CXC motif) receptor 4 and matrix metalloproteinase 1 induction, and epidermal growth factor receptor- and protein kinase B-signaling transactivation, were inhibited by TIF1γ. In addition, we found that the down-regulation of TIF1γ in HCC was caused by hypermethylation of CpG islands in the TIF1γ promoter, and demonstrated that the combination of TIF1γ and phosphorylated Smad2 was a more powerful predictor of poor prognosis. CONCLUSION: TIF1γ regulates tumor growth and metastasis through inhibition of TGF-ß/Smad signaling and may serve as a novel prognostic biomarker in HCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Factores de Transcripción/metabolismo , Animales , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Islas de CpG , Metilación de ADN , Regulación hacia Abajo , Transición Epitelial-Mesenquimal , Femenino , Humanos , Hígado/patología , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cell lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3' UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Regiones no Traducidas 3' , Animales , Neoplasias de la Mama/patología , Proteínas de Ciclo Celular , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Proteínas Asociadas a Microtúbulos , Invasividad Neoplásica/genética , Proteínas NuclearesRESUMEN
BACKGROUND: Activin A, an important member of transforming growth factor-ß superfamily, is reported to inhibit proliferation of mature hepatocyte. However, the effect of activin A on growth of hepatic progenitor cells is not fully understood. To that end, we attempted to evaluate the potential role of activin A in the regulation of hepatic progenitor cell proliferation. RESULTS: Using the 2-acetaminofluorene/partial hepatectomy model, activin A expression decreased immediately after partial hepatectomy and then increased from the 9th to 15th day post surgery, which is associated with the attenuation of oval cell proliferation. Activin A inhibited oval cell line LE6 growth via activating the SMAD signaling pathway, which manifested as the phosphorylation of SMAD2/3, the inhibition of Rb phosphorylation, the suppression of cyclinD1 and cyclinE, and the promotion of p21WAF1/Cip1 and p15INK4B expression. Treatment with activin A antagonist follistatin or blocking SMAD signaling could diminish the anti-proliferative effect of activin A. By contrast, inhibition of the MAPK pathway did not contribute to this effect. Antagonizing activin A activity by follistatin administration enhanced oval cell proliferation in the 2-acetylaminofluorene/partial hepatectomy model. CONCLUSION: Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells.