RESUMO
Traditional observational studies have reported a positive association between constipation and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between constipation and CRC is scarce. In the study, 2-sample Mendelian randomization analysis was conducted to investigate the potential causal relationship between constipation and CRC. Analysis of the results showed that there was no causal association between constipation and CRC, either in European populations (CRC: odds ratio [OR]â =â 1.00, 95% confidence interval [CI] = 0.99-1.00, Pâ =â .49; rectal cancer: ORâ =â 0.99, 95% CI = 0.99-1.00, Pâ =â .79) or in Asian populations (CRC: ORâ =â 1.00, 95% CI = 0.99-1.01, Pâ =â .30). Also there was no inverse causal association between CRC and constipation, either in European populations (CRC: ORâ =â 0.10, 95% CI = 2.76E-03-3.45, Pâ =â .20; rectal cancer: ORâ =â 0.05, 95% CI = 9.14E-07-2.64Eâ +â 03, Pâ =â .59) or in Asian population (CRC: ORâ =â 1.18, 95% CI = 0.92-1.52, Pâ =â .20), there was no horizontal diversity in the instrumental variables in the Mendelian randomization analyses of the present study (all F statistics >10), and no heterogeneity was found in the regression analyses. The findings from bidirectional 2-sample Mendelian randomization analyses indicate that there is no evidence of a bidirectional causal association between constipation and CRC. However, further investigation is warranted through additional clinical studies and trials to thoroughly explore the association between these 2 factors.
Assuntos
Povo Asiático , Neoplasias Colorretais , Constipação Intestinal , Análise da Randomização Mendeliana , População Branca , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , Povo Asiático/genética , Constipação Intestinal/epidemiologia , Constipação Intestinal/genética , População Branca/genética , População Branca/estatística & dados numéricos , Fatores de Risco , Europa (Continente)/epidemiologiaRESUMO
The oxidative-stress-related protein Kelch-like ECH-associated protein 1 (KEAP1) is a substrate articulator of E3 ubiquitin ligase, which plays an important role in the ubiquitination modification of proteins. However, the function of KEAP1 in breast cancer and its impact on the survival of patients with breast cancer remain unclear. Our study demonstrates that KEAP1, a positive prognostic factor, plays a crucial role in regulating cell proliferation, apoptosis, and cell cycle transition in breast cancer. We investigate the underlying mechanism using human tumor tissues, high-throughput detection technology, and a mouse xenograft tumor model. KEAP1 serves as a key regulator of cellular metabolism, the reprogramming of which is one of the hallmarks of tumorigenesis. KEAP1 has a significant effect on mitochondrial biogenesis and oxidative phosphorylation by regulating HSPA9 ubiquitination and degradation. These results suggest that KEAP1 could serve as a potential biomarker and therapeutic target in the treatment of breast cancer.
Assuntos
Neoplasias da Mama , Proliferação de Células , Proteína 1 Associada a ECH Semelhante a Kelch , Ubiquitinação , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Animais , Camundongos , Linhagem Celular Tumoral , Biogênese de Organelas , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteólise , Camundongos Nus , Mitocôndrias/metabolismo , Apoptose , Camundongos Endogâmicos BALB C , Células MCF-7 , Proteínas MitocondriaisRESUMO
BACKGROUND AND OBJECTIVES: This study aimed to assess the utility of Doppler echocardiography in evaluating left ventricular diastolic function, and prognosis in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: A total of 286 SLE patients were selected along with 100 age- and gender-matched healthy individuals who underwent physical examinations. Clinical baseline characteristics were collected. Various Doppler echocardiographic parameters were measured and analyzed, including left ventricular posterior wall thickness (LVPWT), interventricular septal diameter (IVSD), left ventricular mass (LVM), LVM index (LVMI), and others. RESULTS: Compared to the control group, SLE patients exhibited significantly higher levels of C-reactive protein and lower levels of complement (C) 3 and C4 (p < .001). Doppler echocardiographic parameters showed significant differences between SLE patients and healthy controls, including increased LVPWT, IVSD, LVM, LVMI, peak A, PWI + Tei, E/e', TDI-Tei, and decreased e' and E/A (p < .001). Subgroup analyses indicated more severe ventricular diastolic dysfunction in patients with higher SLE activity and those who experienced cardiovascular events. Correlation analysis revealed positive associations of PWI + Tei, TDI-Tei, and GLS with SLE activity and cardiovascular events (p < .01). Multivariate logistic regression analysis identified LVMI, PWI + Tei, TDI-Tei, and GLS as significant predictors of cardiovascular events (p < .05). CONCLUSION: Doppler echocardiography is a valuable tool for the early diagnosis of left ventricular diastolic dysfunction in SLE patients. Key echocardiographic parameters, including LVMI, PWI + Tei, TDI-Tei, and GLS, are effective in predicting cardiovascular events, underscoring the importance of comprehensive cardiac function assessments in these patients.
Assuntos
Ecocardiografia Doppler , Lúpus Eritematoso Sistêmico , Valor Preditivo dos Testes , Disfunção Ventricular Esquerda , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Feminino , Masculino , Adulto , Ecocardiografia Doppler/métodos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Prognóstico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico por imagem , Proteína C-Reativa/análise , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , DiástoleRESUMO
The main impediment to the development of zinc-air batteries is the sluggish kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Transition metal N-doped carbon catalysts offer a promising alternative to noble metal catalysts, with metal-organic framework (MOF)-derived carbon material catalysts being particularly noteworthy. Here, we synthesized MxP-Z-C carbon catalysts by combining two-dimensional (2D) metal porphyrin-based MOFs (MxPMFs, x = Fe, Co, Ni, Mn) and three-dimensional zeolitic imidazole framework-8 (ZIF-8) through electrostatic interaction, followed by carbonization. ZIF-8 was inserted between the layers of MxPMFs to prevent its Π-Π stacking, allowing the active sites to become fully exposed. MxP-Z-C demonstrated an impressive catalytic activity for both the ORR and the OER reactions. Among them, FeP-Z-C showed the best catalytic activity. The half-wave potential for ORR was 0.92 V (vs the reversible hydrogen electrode (RHE)), while the overpotential for the OER was 290 mV. In addition, the zinc-air battery assembled by FeP-Z-C exhibited high power density (133.14 mW cm-2) and significant specific capacity (816 mAh gZn-1), indicating considerable potential as a bifunctional catalyst for electronic devices.
RESUMO
Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare. Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn's disease (CD)] and DD using the Mendelian randomization (MR) analysis. Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy. Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98-1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94-1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92-1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method. Conclusion: This study's findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.
RESUMO
OBJECTIVE: This study aims to evaluate the expression of interleukin 6 (IL-6) in patients with infantile hemangioma (IH) and investigate the role of the IL-6/signal transducers and activators of transduction-3 (STAT3)/hypoxia-inducible factor-1α (HIF-1α) pathways in the progression of IH. METHODS: Serum samples were obtained from the patients with IH and normal infants to measure IL-6 expression. Hemangioma-derived stem cells (HemSCs) were transfected with small interfering RNA (siRNA) targeting IL-6, HIF-1α, or STAT3. Then, cell viability and wound healing assays were conducted. After that, the HemSC tumor mouse model was established. The in vivo anticancer effect of the IL-6 inhibitor was investigated. RESULTS: The patients with IH had much higher IL-6 levels compared with the healthy controls (p = 0.005). HemSCs transfected with IL-6 siRNA had significantly lower viability and migration rates than normal HemSCs. HemSCs transfected with STAT3 siRNA or HIF-1α siRNA had similar tendencies. On tumor-bearing mice, the IL-6 inhibitor treatment significantly delayed tumor growth. Compared with the control group, caspase-3 was significantly increased in the IL-6 inhibitor group (p < 0.05), whereas Ki-67 was decreased in the IL-6 inhibitor group (p < 0.05). In the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, the IL-6 inhibitor group had much higher apoptosis rates than the controls (p < 0.05). CONCLUSION: Our findings indicate that inhibiting the IL-6/STAT3/HIF-1α signaling pathways could suppress IH growth.
Assuntos
Hemangioma , Interleucina-6 , Animais , Camundongos , Hemangioma/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-6/metabolismo , RNA Interferente Pequeno , Transdução de SinaisRESUMO
INTRODUCTION: The aim of the study is to explore the relationship between clinical characteristics and urinary calculus in Xinjiang Uyghur children, and to provide clinical basis for the prevention as well as treatment of urinary stone. MATERIALS AND METHODS: In total, 236 urinary tract stone samples were collected from pediatric patients from February 2017 to April 2019, and those samples were analyzed by infrared spectroscopy. Stone compositions were compared with demographic data. RESULTS: Among the 236 cases, 166 cases were boys (70.34%) and 70 cases were girls (29.66%), with a male-to-female ratio of 2.37:1. A total of 21 kinds of calculi were detected, including 107 cases with six kinds of simple calculi and 129 cases with 15 kinds of mixed calculi. In this study, magnesium ammonium phosphate hexahydrate was only found in boys, and the difference was statistically significant (6.6 vs. 0.0%, p = 0.037). There were statistical differences in the age distribution of children with ammonium hydrogen urate, calcium oxalate, and other stone components (p < 0.05), while there were no statistical differences in the age distribution of children with apatite carbonate, magnesium ammonium phosphate hexahydrate, and anhydrous uric acid. The results showed that there was a significant difference in the localization of calculi between male and female children (upper urinary tract stones: 78.9 vs. 98.6%, p < 0.001). CONCLUSION: Uyghur pediatric patients with urolithiasis were young and the majority of stones was mixed, The main components of calculi were ammonium hydrogen urate, calcium oxalate and apatite carbonate, and there are differences in the localization of calculi between genders.
Assuntos
Compostos de Amônio , Cálculos Urinários , Urolitíase , Criança , Humanos , Feminino , Masculino , Oxalato de Cálcio/análise , Oxalato de Cálcio/química , Estruvita/química , Ácido Úrico/análise , Cálculos Urinários/epidemiologia , Cálculos Urinários/química , Apatitas , CarbonatosRESUMO
OBJECTIVE: The present study aims to explore the correlation of the transforming growth factor ß (TGF-ß), drosophila mothers against decapentaplegic protein gene (SMAD) 2/3/4, and leukemia inhibitory factors (LIF) with the cyst formation of hepatic Echinococcus granulosus in young children. METHODS: A total of 40 patients who met the diagnostic criteria for children's hydatid disease in people's Hospital of Xinjiang Uygur Autonomous Region between January 2020 and June 2021 were enrolled a s the study subjects. The cystic fluid of these children was collected as the case group and the corresponding infected viscera or pericystic tissue as the control group, with 40 cases in each group. In vitro cultured protoscolice of hydatid cyst, four groups including control group, LIF siRNA group, LIF factor group and SMAD4 siRNA group were divided by inhibiting TGF-ß/SMADs signal pathway. Each assay was performed in triplicate. The expression of TGF-ß, SMAD2/3/4 and LIF were detected. RESULTS: The results of the clinical trial showed that the contents of SMAD2 and SMAD3 were increased in the case group compared with the control group; the differences were statistically significant (P < 0.05). The expression levels of TGF-ß, Smad4, and LIF increased in the case group compared with the control group; however, the differences were not statistically significant. The results of further in vitro experiments, the expression levels of TGF-ß, SMAD 2/3/4, and LIF after adding siRNA to interfere with Smad4 decreased in the case group compared with the control group; the differences were statistically significant (P < 0.05). Compared with the control group, the expression levels of TGF-ß, SMAD2/3/4, and LIF increased after treatment with added LIF in the case group, and the expression levels of TGF-ß, SMAD2/3/4, and LIF decreased after adding siRNA to interfere with LIF in the case group; the differences were all statistically significant (P < 0.05). CONCLUSION: SMAD2 and SMAD3 have a certain clinical relevance with hydatidosis in young children. The LIF expression level may be related to the cystic transformation of protoscoleces. It has been suggested that the TGF-ß/Smads/LIF signaling pathway may be present in the process of protoscoleces cyst formation; this provides a research basis for the prevention and treatment of post-infection parasitism of E. multilocularis eggs in young children.
Assuntos
Cistos , Echinococcus , Animais , RNA Interferente Pequeno , Fator de Crescimento Transformador betaRESUMO
Vaccines are needed to disrupt or prevent continued outbreaks of filoviruses in humans across Western and Central Africa, including outbreaks of Marburg virus (MARV). As part of a filovirus vaccine product development plan, it is important to investigate dose response early in preclinical development to identify the dose range that may be optimal for safety, immunogenicity, and efficacy, and perhaps demonstrate that using lower doses is feasible, which will improve product access. To determine the efficacious dose range for a manufacturing-ready live recombinant vesicular stomatitis virus vaccine vector (rVSV∆G-MARV-GP) encoding the MARV glycoprotein (GP), a dose-range study was conducted in cynomolgus macaques. Results showed that a single intramuscular injection with as little as 200 plaque-forming units (PFUs) was 100% efficacious against lethality and prevented development of viremia and clinical pathologies associated with MARV Angola infection. Across the vaccine doses tested, there was nearly a 2000-fold range of anti-MARV glycoprotein (GP) serum IgG titers with seroconversion detectable even at the lowest doses. Virus-neutralizing serum antibodies also were detected in animals vaccinated with the higher vaccine doses indicating that vaccination induced functional antibodies, but that the assay was a less sensitive indicator of seroconversion. Collectively, the data indicates that a relatively wide range of anti-GP serum IgG titers are observed in animals that are protected from disease implying that seroconversion is positively associated with efficacy, but that more extensive immunologic analyses on samples collected from our study as well as future preclinical studies will be valuable in identifying additional immune responses correlated with protection that can serve as markers to monitor in human trials needed to generate data that can support vaccine licensure in the future.
RESUMO
BACKGROUND: To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a single vaccine dose, we developed a SARS-CoV-2 candidate vaccine using the live vesicular stomatitis virus (VSV) chimeric virus approach previously used to develop a licensed Ebola virus vaccine. METHODS: We generated a replication-competent chimeric VSV-SARS-CoV-2 vaccine candidate by replacing the VSV glycoprotein (G) gene with coding sequence for the SARS-CoV-2 Spike glycoprotein (S). Immunogenicity of the lead vaccine candidate (VSV∆G-SARS-CoV-2) was evaluated in cotton rats and golden Syrian hamsters, and protection from SARS-CoV-2 infection also was assessed in hamsters. FINDINGS: VSV∆G-SARS-CoV-2 delivered with a single intramuscular (IM) injection was immunogenic in cotton rats and hamsters and protected hamsters from weight loss following SARS-CoV-2 challenge. When mucosal vaccination was evaluated, cotton rats did not respond to the vaccine, whereas mucosal administration of VSV∆G-SARS-CoV-2 was found to be more immunogenic than IM injection in hamsters and induced immunity that significantly reduced SARS-CoV-2 challenge virus loads in both lung and nasal tissues. INTERPRETATION: VSV∆G-SARS-CoV-2 delivered by IM injection or mucosal administration was immunogenic in golden Syrian hamsters, and both vaccination methods effectively protected the lung from SARS-CoV-2 infection. Hamsters vaccinated by mucosal application of VSV∆G-SARS-CoV-2 also developed immunity that controlled SARS-CoV-2 replication in nasal tissue. FUNDING: The study was funded by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA. Parts of this research was supported by the Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency (DTRA) of the US Department of Defense.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Cricetinae , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Mesocricetus , SARS-CoV-2 , Vírus da Estomatite Vesicular Indiana/genética , Imunogenicidade da VacinaRESUMO
During the pandemic era, quarantines might potentially have negative effects and disproportionately exacerbate health condition problems. We conducted this cross-sectional, national study to ascertain the prevalence of constant pain symptoms and how quarantines impacted the pain symptoms and identify the factors associated with constant pain to further guide reducing the prevalence of chronic pain for vulnerable people under the pandemic. The sociodemographic data, quarantine conditions, mental health situations and pain symptoms of the general population were collected. After adjusting for potential confounders, long-term quarantine (≥15 days) exposures were associated with an increased risk of constant pain complaints compared to those not under a quarantine (Odds Ratio (OR): 1.26; 95% Confidence Interval (CI): 1.03, 1.54; p = 0.026). Risk factors including unemployment (OR: 1.55), chronic disease history (OR: 2.38) and infection with COVID-19 (OR: 2.15), and any of mental health symptoms including depression, anxiety, insomnia and PTSD (OR: 5.44) were identified by a multivariable logistic regression. Additionally, mediation analysis revealed that the effects of the quarantine duration on pain symptoms were mediated by mental health symptoms (indirect effects: 0.075, p < 0.001). These results advocated that long-term quarantine measures were associated with an increased risk of experiencing pain, especially for vulnerable groups with COVID-19 infection and with mental health symptoms. The findings also suggest that reducing mental distress during the pandemic might contribute to reducing the burden of pain symptoms and prioritizing interventions for those experiencing a long-term quarantine.
RESUMO
BACKGROUND: Ganglion impar block alone or pulsed radiofrequency alone are effective options for treating perineal pain. However, ganglion impar block combined with pulsed radiofrequency (GIB-PRF) for treating perineal pain is rare and the puncture is usually performed with X-ray or computed tomography guidance. AIM: To evaluate the safety and clinical efficacy of real-time ultrasound-guided GIB-PRF in treating perineal pain. METHODS: Thirty patients with perineal pain were included and were treated by GIB-PRF guided by real-time ultrasound imaging between January 2015 and December 2016. Complications were recorded to observe the safety of the ultrasound-guided GIB-PRF procedure, and visual analogue scale (VAS) scores at 24 h before and after treatment and 1, 3, and 6 mo later were analyzed to evaluate clinical efficacy. RESULTS: Ultrasound-guided GIB-PRF was performed successfully in all patients, and no complications occurred. Compared with pretreatment scores, the VAS scores were significantly lower (P < 0.05) at the four time points after treatment. The VAS scores at 1 and 3 mo were slightly lower than those at 24 h (P > 0.05) and were significantly lower at 6 mo after treatment (P < 0.05). There was a tendency toward lower VAS scores at 6 mo after treatment compared with those at 1 and 3 mo (P > 0.05). CONCLUSION: Ultrasound-guided GIB-PRF was a safe and effective way to treat perineal pain. The 6-mo short-term clinical efficacy was favorable, but the long-term outcomes need future study.
RESUMO
The brain is one of the most important and intricate organs in our bodies. Interpreting brain function and illustrating the changes and molecular mechanisms during physiological or pathological processes are essential but sometimes difficult to achieve. In addition to histology, ethology and pharmacology, the development of transcriptomics alleviates this condition by enabling high-throughput observation of the brain at various levels of anatomical specificity. Moreover, because human brain samples are scarce, the brains of nonhuman primates are important alternative models. Here in this review, we summarize the applications of transcriptomics in nonhuman primate brain studies, including investigations of brain development, aging, toxic effects and diseases. Overall, as a powerful tool with developmental potential, transcriptomics has been widely utilized in neuroscience.
Assuntos
Envelhecimento/fisiologia , Encefalopatias/genética , Encéfalo/crescimento & desenvolvimento , Primatas/fisiologia , Transcriptoma/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encefalopatias/patologia , Modelos Animais de Doenças , Etanol/efeitos adversos , Humanos , Metanfetamina/efeitos adversos , Neurociências/métodos , RNA-Seq , Sevoflurano/efeitos adversos , Transcriptoma/efeitos dos fármacos , Ácido Valproico/efeitos adversosRESUMO
W922, a novel PI3K/Akt/mTOR pathway inhibitor, exhibits efficient antitumor effects on HCT116, MCF7 and A549 human cancer cells compared with other synthesized compounds. The present study aimed to investigate its antitumor effects on colorectal cancer cells. A total, of seven different colorectal cell lines were selected to test the antiproliferation profile of W922, and HCT116 was found to be the most sensitive cell line to the drug treatment. W922 inhibited HCT116 cell viability and cell proliferation in vitro in concentration and timedependent manners. Furthermore, W922 suppressed the tumor growth in a xenograft mouse model and exhibited low toxicity. The proteomic alterations in W922treated HCT116 cells were found to be associated with cell cycle arrest, negative regulation of signal transduction and lysosomerelated processes. W922 caused cell cycle arrest of HCT116 cells in G0G1 phase, but only triggered slight apoptosis. In addition, the PI3K/Akt/mTOR signaling proteins were dephosphorylated upon W922 treatment. It has been reported that inhibition of mTOR is relevant to autophagy, and the present results also indicated that W922 was involved in autophagy induction. An autophagy inhibitor, chloroquine, was used to cotreat HCT116 cells with W922, and it was identified that the cell cycle arrest was impaired. Moreover, cotreatment of W922 and chloroquine led to a significant population of apoptotic cells, thus providing a promising therapeutic strategy for colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autofagia/efeitos dos fármacos , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Neoplasias Colorretais/patologia , Sinergismo Farmacológico , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Catheter ablation for ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has significantly evolved over the past decade. However, different ablation strategies showed inconsistency in acute and long-term outcomes. METHODS: We searched the databases of Medline, Embase and Cochrane Library through October 17, 2019 for studies describing the clinical outcomes of VT ablation in ARVC. Data including VT recurrence, all-cause mortality, acute procedural efficacy and major procedural complications were extracted. A meta-analysis with trial sequential analysis was further performed in comparative studies of endo-epicardial versus endocardial-only ablation. RESULTS: A total of 24 studies with 717 participants were enrolled. The literatures of epicardial ablation were mainly published after 2010 with total ICD implantation of 73.7%, acute efficacy of 89.8%, major complication of 5.2%, follow-up of 28.9 months, VT freedom of 75.3%, all-cause mortality of 1.1% and heart transplantation of 0.6%. Meta-analysis of 10 comparative studies revealed that compared with endocardial-only approach, epicardial ablation significantly decreased VT recurrence (OR: 0.50; 95% CI: 0.30-0.85; P = 0.010), but somehow increased major procedural complications (OR: 4.64; 95% CI: 1.28-16.92; P= 0.02), with not evident improvement of acute efficacy (OR: 2.74; 95% CI: 0.98-7.65; P = 0.051) or all-cause mortality (OR: 0.87; 95% CI: 0.09-8.31; P = 0.90). CONCLUSION: Catheter ablation for VT in ARVC is feasible and effective. Epicardial ablation is associated with better long-term VT freedom, but with more major complications and unremarkable survival or acute efficacy benefit.
RESUMO
BACKGROUND: Information on the relationship between red blood cell distribution width (RDW) and atrial fibrillation (AF) in patients with essential hypertension are scarce. The study aimed to assess the relationship between AF and RDW in hypertensive patients. METHODS: We enrolled 432 hypertensive patients, including 350 AF patients and 82 patients as controls. Patients' demographic, clinical, laboratory and echocardiographic characteristics were recorded. The AF patients were further divided into the persistent and paroxysmal AF subgroups. Electrocardiograms were monitored to identify the cardiac rhythm during blood sampling, and based on the rhythm, the paroxysmal AF group was categorized into the presence (with AF rhythm during blood sampling) and absence (with sinus rhythm during blood sampling) groups. RESULTS: The AF group had elevated RDW levels than the controls (12.7% ± 0.8% vs. 12.4% ± 0.7%, P = 0.002), and the persistent AF subgroup had higher RDW levels than the paroxysmal AF subgroup (12.9% ± 0.8% vs. 12.6% ± 0.8%, P = 0.007). Furthermore, in the paroxysmal AF group, the presence group had higher RDW levels than the absence group (13.0% ± 0.6% vs. 12.5% ± 0.9%, P = 0.001). There was no significant difference in RDW levels between the persistent AF subgroup and presence group of the paroxysmal AF subgroup (P = 0.533) and between the absence group of the paroxysmal AF subgroup and control group (P = 0.262). In multivariate regression analysis, in hypertensive patients, the presence of AF rhythm is an independent predictor for increased RDW concentration (P = 0.001). CONCLUSIONS: The RDW may be associated with the presence of AF rhythm, which implies the importance of maintaining the sinus rhythm in hypertensive patients.
RESUMO
Growth hormone (GH) is the most important endocrine factor to regulate somatic growth. Spotted scat (Scatophagus argus) is a famous marine aquaculture species in China with a typical sexual growth dimorphism in which females grow faster and larger than males. In this study, gh messenger RNA (gh mRNA) and GH protein expression were examined in the pituitary glands of female and male spotted scat. Based on qPCR analysis, gh mRNA was mainly expressed in the pituitary gland, and weakly in the gonads and hypothalamus. Furthermore, gh mRNA expression in the pituitary gland was significantly higher in females at stages II-IV than in males at stages III-V. In addition, gh mRNA was highly expressed in the ovary and testis during mature development stages. In this study, spotted scat GH polyclonal antibody was produced. Western blot analysis showed that the molecular weight of spotted scat GH was about 21 KDa. Immunohistochemistry (IHC) in pituitary glands showed that GH was mainly expressed in the proximal pars distal (PPD) and a few cells were distributed in the rostral pairs distal (RPD). After injecting 17ß-Estradiol (E2) in vivo, gh mRNA expression was significantly up-regulated in the pituitary gland, whereas igf1 and ghr1 mRNA levels were down-regulated in the liver, which might regulate gh mRNA expression in the pituitary gland. These results provide valuable insight into the molecular mechanisms of E2 regulating gh expression in spotted scat.
Assuntos
Estradiol/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Perciformes/crescimento & desenvolvimento , Perciformes/genética , Animais , Feminino , Masculino , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/metabolismoRESUMO
In this study, the double-layered nHA and PCL/nHA coatings were prepared on the substrate of Mg66Zn28Ca6 amorphous alloy. The phase composition and morphological were analyzed by Scanning electron microscopy, Energy dispersive spectrometry and X-ray diffraction. The electrochemical properties of these samples were measured on electrochemical workstation. The degradation rate was evaluated by measuring the pH value and weight loss. Experiment results show that the outer composite PCL/nHA coating is a porous structure, where the porosity and pore size could be easily controlled by adding nHA. The combined properties of double-layered nHA and PCL/nHA coating can control the degradation of the Mg66Zn28Ca6 amorphous alloy in the scheduled time. Moreover,the cell co-culture and cell adhesion tests show that the double-layered nHA and PCL/2%nHA coating possesses the best cytocompatibility with cell organization. The above experiments have demonstrated that the Mg66Zn28Ca6 amorphous alloy which was coated with PCL/nHA composite coating have good mechanical properties, good corrosion resistance and perfect cytocompatibility. It can be used as a potential novel biomaterial for bone tissue engineering.
Assuntos
Ligas , Materiais Revestidos Biocompatíveis , Ligas/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Corrosão , Magnésio , Propriedades de Superfície , ZincoRESUMO
Gonadotropin-releasing hormone (GnRH) is a key neuropeptide of the reproductive system. However, little is known about the role of GnRH in the spotted scat (Scatophagus argus). Here, three GnRH subtypes (cGnRH-II, sGnRH, and sbGnRH) were identified in the spotted scat. cGnRH-II and sGnRH were only expressed in the brains and gonads of both male and female fish, exhibiting a tissue-specific expression pattern, while sbGnRH was expressed at different transcription levels in all examined tissues. During ovarian maturation, hypothalamus-associated sbGnRH was upregulated, while the expression of sGnRH was variable and cGnRH-II first increased and then decreased. In vivo experiments showed that sbGnRH significantly promoted the expression of fsh and lh genes in a dose-dependent manner and exhibited a desensitization effect on lh expression at high concentrations. For sGnRH and cGnRH-II, only high concentrations could induce fsh and lh expression. Furthermore, treatment with highly concentrated sbGnRH peptide also induced fsh and lh expression, whereas the sGnRH and cGnRH-II peptides only induced fsh expression in vitro. 17ß-Estradiol (E2) significantly inhibited the expression of sbGnRH mRNA in a dose-dependent manner and did not impact sGnRH and cGnRH-II mRNA levels in vivo or in vitro. The inhibitory effect of E2 on sbGnRH expression was attenuated by the estrogen receptor (ER) broad-spectrum antagonist (fulvestrant) and the ERα-specific antagonist (methyl-piperidinopyrazole), respectively, implying that the feedback regulation on sbGnRH is mediated via ERα. This study provides a theoretical basis for the reproductive endocrinology of the spotted scat by studying GnRH.