RESUMO
INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study employed bidirectional Mendelian randomization (MR) analysis to investigate the interaction between nine phenotypes, namely hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements, including total surface area (SA), average thickness (TH), and the SA and TH of 34 regions based on the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. False discovery rate adjustment was applied to p-values (q-values) in the analyses for regional cortical structure. RESULTS: A total of 1260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (qâ¯=â¯0.018) and the superior frontal lobe (qâ¯=â¯0.018), while hypertension was associated with changes in the TH of the lateral occipital region (qâ¯=â¯0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 15 regions and four areas exhibited significant effects on blood pressure and AF risk, respectively (qâ¯<â¯0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are responsible for cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.
RESUMO
BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.
RESUMO
The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], Pâ =â .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interactionâ =â .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interactionâ =â .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Masculino , Feminino , Idoso , Peptídeo Natriurético Encefálico , Volume Sistólico , Prognóstico , Fragmentos de Peptídeos , BiomarcadoresRESUMO
Liquid-liquid phase separation (LLPS) plays a key role in the regulation of life activities. Here, we reported a protein from Synechocystis sp. PCC 6803 and annotated as Slr0280. To obtain a water-soluble protein, we deleted the N-terminus transmembrane domain and named it Slr0280Δ. Slr0280Δ with high concentration can undergo LLPS at a low temperature in vitro. It belongs to the phosphodiester glycosidase family of proteins and has a segment of a low-complexity sequence region (LCR), which is thought to regulate the LLPS. Our results show that electrostatic interactions impact the LLPS of Slr0280Δ. We also acquired the structure of Slr0280Δ, which has many grooves on the surface with a large distribution of positive and negative charges. This may be advantageous for the LLPS of Slr0280Δ through electrostatic interactions. Furthermore, the conserved amino acid (arginine at position 531) located on the LCR is important for maintaining the stability of Slr0280Δ as well as LLPS. Our research indicated that the LLPS of proteins can be transformed into aggregation by changing the surface charge distribution.
Assuntos
Domínios ProteicosRESUMO
OBJECTIVE: This meta-analysis was conducted to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with surgery and preoperative chemoradiotherapy (CRT) combined with surgery for locally advanced rectal cancer. METHODS: PubMed, EMBASE and Cochrane Library were searched to collect published randomized controlled trials of preoperative radiotherapy or preoperative CRT combined with surgery for the treatment of locally advanced rectal cancer. Studies were screened according to inclusion and exclusion criteria, and quality was evaluated; RevMan 5.3 software was used for meta-analysis. RESULTS: In total, 7 related studies involving 3100 patients with locally advanced rectal cancer were evaluated. The pathological complete response rate, negative lymph node rate, R0 resection rate, and incidence of grade III/IV adverse reactions were lower in the RT group than in the CRT group. In the absence of postoperative chemotherapy, the 5-year local recurrence rate of RT was higher than that of CRT, but there was no significant difference between the groups among those who underwent postoperative chemotherapy. Moreover, there was no significant difference between the groups with regard to the 5-year survival rate, anal-preserving rate, or incidence of anastomotic leakage. CONCLUSION: Preoperative CRT is better than preoperative RT for the treatment of advanced rectal cancer, though the adverse reaction rate is higher.
Assuntos
Quimiorradioterapia , Neoplasias Retais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
Background: To assess the link between serum potassium ( K + ) and all-cause mortality in hospitalized heart failure (HF) patients. Methods: Hospitalized HF patients (n = 3114) were analyzed at the Fuwai Hospital Heart Failure Center. Before discharge, HF patients were divided into four groups according to the K + level quartiles: K + ≤ 3.96 mmol/L (Q1), 3.96 < K + ≤ 4.22 mmol/L (Q2), 4.22 < K + ≤ 4.52 mmol/L (Q3), and K + > 4.52 mmol/L (Q4). At 90 days, 2 years, and maximal follow-up, all-cause mortality was the primary outcome. Results: Patients with HF in the Q4 group had worse cardiac function, higher N-terminal pro-B-type natriuretic peptide levels, lower left ventricular ejection fractions and lower estimated glomerular filtration rates than patients in the Q2 group. In the multivariate-adjusted Cox analysis, the mortality assessed during the 90-day, 2-year, and maximal follow-up examinations increased in the Q4 group of HF patients but not in the Q1 and Q3 groups. The Q4 group had a 28% (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.09-1.49, p = 0.002) higher risk of all-cause mortality at maximum follow-up. Hypokalemia and hyperkalemia were linked to increased HF mortality risk at the 90-day, 2-year, and maximal follow-up periods. Conclusions: Serum K + levels had a J-shaped association with all-cause mortality in HF patients. Both hypokalemia and a K + level of > 4.52 mmol/L were associated with increased all-cause mortality in the short term and long term, suggesting a narrow target K + range in HF patients. Clinical Trial Registration: Unique Identifier: NCT02664818; URL: clinicaltrials.gov.
RESUMO
PURPOSE: The study aims to systematically evaluate the clinical efficacy after 8 weeks (long interval, LI) between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. METHODS: The PubMed database, EMBASE database, and the Cochrane Library (deadline: September 25, 2021) were searched to select clinical studies that compared two intervals between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: after 8 weeks (long interval, LI) and within 8 weeks (short interval, SI). The included studies were screened and evaluated according to the inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3 software. RESULTS: Eighteen studies were included, with 9070 cases in the LI group and 14,207 cases in the SI group. The analysis results showed that the pathologic complete response (PCR) rate in the LI group was higher than that in the SI group (P < 0.00001). There was no significant difference in the R0 resection rate (P = 0.85), anal preservation rate (P = 0.89), morbidity rate (P = 0.60), anastomotic leakage rate (P = 0.06), operation time (P = 0.58), local recurrence rate (P = 0.56), distant metastasis rate (P = 0.32), or overall survival (OS) rate (P = 0.17) between the two groups. CONCLUSION: A longer interval between neoadjuvant chemoradiotherapy and surgery can improve the PCR rate; however, it has no significant impact on the clinical efficacy or long-term prognosis. Due to some limitations in the number and quality of the studies, these findings still need to be further verified by multicenter, large-sample high-quality RCTs in the future.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Quimiorradioterapia , Humanos , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Reto , Resultado do TratamentoRESUMO
Cooperative coacervation of a porphyrin and a polycation electrolyte gives birth to photoactive membraneless protocells via liquid-liquid phase separation, where J-aggregates are formed to offer energy transduction pathways, rendering an adaptive platform for confining photocatalytic reactions within protocell compartments.
Assuntos
Eletrólitos/química , Polieletrólitos/química , Porfirinas/química , Estrutura Molecular , Tamanho da Partícula , Processos FotoquímicosRESUMO
OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Sulfetos/uso terapêutico , COVID-19/mortalidade , Combinação de Medicamentos , Humanos , Indóis/efeitos adversos , Lopinavir/efeitos adversos , Ritonavir/efeitos adversos , SARS-CoV-2/efeitos dos fármacos , Sulfetos/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide life-threatening pandemic. Lianhua Qingwen is believed to possess the ability to treat or significantly improve the symptoms of COVID-19. These claims make it important to systematically evaluate the effects of using Lianhua Qingwen with Western medicine to treat COVID-19. OBJECTIVE: To evaluate the safety and efficacy of combination therapy, employing Lianhua Qingwen with Western medicine, to treat COVID-19, using a meta-analysis approach. SEARCH STRATEGY: China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the effect of Lianhua Qingwen-Western medicine combination therapy in the treatment of COVID-19. INCLUSION CRITERIA: (1) Research object: hospitalized patients meeting the diagnostic criteria of COVID-19 were included. (2) Intervention measures: patients in the treatment group received Lianhua Qingwen treatment combined with Western medicine, while the control group received either Western medicine or Chinese medicine treatment. (3) Research type: randomized controlled trials and retrospective study were included. DATA EXTRACTION AND ANALYSIS: Two researchers extracted the first author, the proportion of males and females, age, body temperature, course of treatment, rate of disappearance of main symptoms, duration of fever, adverse reactions, and total effectiveness from the literature. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect value for count data, and mean difference (MD) and 95% CI were used as the effect value for measurement data. RESULTS: Six articles met the inclusion criteria, including a total of 856 COVID-19 patients. The meta-analysis showed that Lianhua Qingwen combination therapy achieved higher rates of fever reduction (OR = 3.43, 95% CI [1.78, 6.59], P = 0.0002), cough reduction (OR = 3.39, 95% CI [1.85, 6.23], P < 0.0001), recovery from shortness of breath (OR = 10.62, 95% CI [3.71, 30.40], P < 0.0001) and recovery from fatigue (OR = 2.82, 95% CI [1.44, 5.53], P = 0.003), higher total effectiveness rate (OR = 2.51, 95% CI [1.73, 3.64], P < 0.00001), and shorter time to recovery from fever (MD = -1.00, 95% CI [-1.04, 0.96], P < 0.00001), and did not increase the adverse reaction rate (OR = 0.65, 95% CI [0.42, 1.01], P = 0.06), compared to the single medication control. CONCLUSION: The Lianhua Qingwen and Western medicine combination therapy is highly effective for COVID-19 patients and has good clinical safety. As only a small number of studies and patients were included in this review, more high-quality, multicenter, large-sample-size, randomized, double-blind, controlled trials are still needed for verification.
Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , SARS-CoV-2RESUMO
Nowadays, continuous efforts have been devoted to searching highly efficient electrochemiluminescence (ECL) emitters for applications in clinical diagnosis and food safety. In this work, triazinyl-based hydrogen bond organic frameworks (Tr-HOFs) were synthesized by N···H hydrogen bond self-assembly aggregation, where 6,6'-(1,4-phenylene)bis(1,3,5-triazine-2,4-diamine) (phenyDAT) was prepared via the cyclization reaction and behaved as a novel ligand. Impressively, the resulting Tr-HOFs showed strong ECL responses with highly enhanced ECL efficiency (21.3%) relative to the Ru(bpy)32+ standard, while phenyDAT hardly showed any ECL emission in aqueous phase. The Tr-HOFs innovatively worked as a new ECL luminophore to construct a label-free biosensor for assay of kanamycin (Kana). Specifically, the ECL response greatly weakened upon assembly of captured DNA with ferrocene (cDNA-Fc) onto the Tr-HOFs-modified electrode, while the ECL signals were adversely recovered by releasing linked DNA (L-DNA) from double-stranded DNA (dsDNA, hybridization of aptamer DNA (aptDNA) with L-DNA) due to the specific recognition of Kana with the aptDNA combined by the linkage of L-DNA and cDNA-Fc on the electrode. The as-built sensor showed a broadened linear range (1 nM-10 µM) and a limit of detection (LOD) down to 0.28 nM, which also displayed satisfactory results in the analysis of Kana in the milk and diluted human serum samples. This work offers a novel pathway to design an ECL emitter with organic molecules, holding great promise in biomedical analysis and food detection.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Humanos , Ligação de Hidrogênio , Limite de Detecção , Medições LuminescentesRESUMO
Nowadays, brain natriuretic peptide (BNP-32) is fundamental to early cardiovascular clinical diagnosis, whose accurate assay is of significance by photoelectrochemistry (PEC) for the low background and high precision. Herein, a novel enhanced PEC platform was built by successive deposition of N-doped ZnO nanopolyhedra (N-ZnO NP) and protoporphyrin IX (PPIX). Specifically, the N-ZnO NP with a narrow bandgap of 2.60 eV was synthesized by direct calcination of zeolitic imidazole framework-8 (ZIF-8), and performed as the substrate to enhance the photocurrents of PPIX (as photosensitizer) whose photoelectron transfer pathway and enhanced PEC mechanism were studied in detail. Under such foundation, a label-free PEC aptasensor was developed by deposition of DNA aptamer onto the PEC platform and then ultrasensitive assay of BNP-32 based on a "signal off" model. The biosensor showed a wide linear range (1 pg mL-1- 0.1 µg mL-1) with a limit of detection (LOD) as low as 0.14 pg mL-1. This doping technique of ZnO nanomaterials provides some valuable guidelines for synthesis of advanced PEC probes in bioanalysis.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Porfirinas , Óxido de Zinco , Peptídeo Natriurético EncefálicoRESUMO
In this work, metal-organic frameworks (MOFs) are utilized as effective ECL coreactant accelerator to enhance the ECL responses of N-(aminobutyl)-N-(ethylisoluminol) (ABEI). Zn-based MOFs (MOF-Zn-1) were prepared by chelating Zn ions with melamine and thiophenedicarboxylic acid (TPDA), which observably accelerated the electrocatalytic oxidation of tripropylamine (TPA). Then, ABEI-MOF-Zn-1 as a high-performance ECL emitter was synthesized via an amide reaction between ABEI and mercaptopropionic acid (MPA) modified MOF-Zn-1. Strikingly, the ABEI-MOF-Zn-1 showed the 18-fold increase in the ECL signals relative to pure ABEI by using TPA as a coreactant. Moreover, ferrocene (Fc) as a quencher was first linked with capture DNA (cDNA), and then used to modify the ABEI-MOF-Zn-1, thereby constructing a label-free ECL biosensor. After the linkage between chloramphenicol (CAP) and aptamer DNA (aptDNA), the ECL response was definitely recovered by releasing L-DNA from double-stranded DNA (dsDNA, hybridization of aptDNA and L-DNA). The resultant sensor showed a wide linear range of 1.00 nM-0.10 mM (R2 = 0.99) and a low limit of detection (LOD) down to 0.11 nM for detecting CAP. This work developed a novel pattern to design an efficient ECL enhanced emitter, coupled by expanding its potential applications in clinical diagnosis.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Cloranfenicol , Técnicas Eletroquímicas , Limite de Detecção , Medições LuminescentesRESUMO
The present study systematically evaluated the clinical effects of mesh-plug and Lichtenstein herniorrhaphy in the treatment of primary inguinal hernia. PubMed, Embase, and the Cochrane Library (cut-off: May 25, 2020) databases were searched to select randomized controlled trials (RCTs) on mesh-plug and Lichtenstein herniorrhaphy for the treatment of primary inguinal hernia. Articles that met the inclusion criteria were screened and evaluated for quality. RevMan 5.3 software was used to perform a meta-analysis of operation time, discomfort in the inguinal region, haematoma, seroma, infection, time to return to normal activities, incidence of postoperative chronic pain, and recurrence rate. Eleven RCTs with 1457 patients in the mesh-plug group and 1472 in the Lichtenstein group were included. Meta-analysis showed that the mesh-plug herniorrhaphy group had a shorter operation time than the Lichtenstein herniorrhaphy group [P < 0.0001] but a longer time to return to normal activities after surgery [MD = 1.48, 95% CI (0.58, 2.38), P = 0.001]. There were no significant differences in postoperative discomfort in the inguinal region [P = 0.90], seroma [P = 0.10], haematoma [P = 0.27], infection [P = 0.40], incidence of postoperative chronic pain [P = 0.90], or recurrence rate [P = 0.77] between groups. Mesh-plug herniorrhaphy requires a shorter operation time than Lichtenstein herniorrhaphy, and there is no significant difference in postoperative complications or recurrence rate between the two methods. Clinical trial registration: INPLASY202070088. Meta-analysis of mesh -plug repair and Lichtenstein repair in the treatment of primary inguinal hernia.
Assuntos
Dor Crônica , Hérnia Inguinal , Hérnia Inguinal/cirurgia , Herniorrafia , Humanos , Dor Pós-Operatória/epidemiologia , Recidiva , Telas Cirúrgicas , Resultado do TratamentoRESUMO
This is the first study exploring the effects of persistent Cr(VI) treatment on microbial communities and function as well as the process efficiency of an A2O system. The inhibitory effect was clearly higher at a high Cr(VI) concentration than a low Cr(VI) concentration, and different Cr(VI) concentrations had distinct effects on the microbial communities as well as on the performance efficiency of the system. Functional annotation analysis indicated that Cr(VI) stress inhibited most of the metabolic pathway and functional genes of the microbial communities, especially those involved in the denitrification pathway. Network analysis was used to investigate the co-occurrence patterns between denitrification genes and microbial taxa; the results indicated that microorganisms with functional genes had high diversity and were adversely affected by Cr(VI) exposure. This study is the first to establish a relationship between Cr(VI) stress and microbial communities and function as well as to determine the underlying mechanisms and roles of Cr(VI) in A2O sludge.
Assuntos
Cromo/toxicidade , Microbiota/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Reatores Biológicos , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota/genética , RNA Ribossômico 16S , Esgotos/microbiologiaRESUMO
RATIONALE: Squamous carcinoma is the most common malignancy of vagina. Adenoid cystic carcinoma (ACC) in the vagina is very rare. PATIENT CONCERNS: In the present study, we present a 45-year-old woman with a palpable swelling in the vagina. The patient reported body paresthesia, chest congestion, expiratory dyspnea, and itching in the thigh root. DIAGNOSIS: The ultrasound results revealed inhomogeneous echoes of the muscular layer in the middle and distal of the vagina, and probed a slightly richer blood flow signal. Then biopsy was performed. On microscopic examination, it was observed that tumor cells were arranged in a tubular or cribriform pattern, and exhibited a consistent size, small nuclei, and nuclear fission. The myoepithelium was lined around the glandular cavity, but the myoepithelium was tumorous. Immunohistochemistry was performed for further verification. Vimentin was positive in mesenchyme and CK-P was positive in epithelial cells. P63 and calponin were spotted, which were focal positive around the glandular cavity. Finally, the patient was diagnosed as ACC. INTERVENTIONS: At last, the patient chose chemoradiotherapy, not surgical excision. OUTCOMES: The patient is alive and well 13 months after the initial diagnosis. LESSONS: ACC in the vagina is extremely rare. To our knowledge, this report is the first case of ACC arising from the vagina in English-language literature. Extensive surgical section of the tumour and chemoradiotherapy are recommended for therapy. Because of rarity, the prognosis of ACC in vagina is not known.
Assuntos
Carcinoma Adenoide Cístico/patologia , Neoplasias Vaginais/patologia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Vaginais/diagnóstico , Neoplasias Vaginais/tratamento farmacológicoRESUMO
Cervical cancer (CC) is the third most common cancer and the fourth leading cause of malignancy-related mortality in women worldwide. In addition, epithelial-mesenchymal transition (EMT) has been generally studied in tumor metastasis researches in recent years. Cysteine-rich intestinal protein 1 (CRIP1) is differently expressed in human cancer cells. However, the role it plays in CC has not been revealed at present. Preliminary experiments have shown that CRIP1 had a higher expression in CC tissues, compared with adjacent noncancerous tissues. Real-time PCR and western blot were performed to analyze CRIP1 expression in CC cell lines. CRIP1 transient transfection vector and siRNA were constructed. Further analysis revealed the promotion effects of CRIP1 on the cell migration and invasion of CC in vitro (Pâ¯<â¯0.01). In addition, western blot was performed to show that CRIP1 mediates EMT by means of EMT marker detection. The expression of CRIP1 and ßcatenin in CC tissues was analyzed by immunohistochemistry (IHC). Interestingly, CRIP1 and ßcatenin were both highly expressed in CC tissues (Pâ¯<â¯0.01). Furthermore, CRIP1 increased the protein expression level of c-myc, cyclinD-1 and cytoplasmic ßcatenin, which are indicators for activating the Wnt/ßcatenin signaling pathway. In conclusion, CRIP1 promotes cell migration and invasion, mediates EMT and activates the Wnt/ßcatenin signaling pathway in CC.
Assuntos
Proteínas de Transporte/metabolismo , Transição Epitelial-Mesenquimal , Proteínas com Domínio LIM/metabolismo , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Adulto , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ciclina D1/metabolismo , Citoplasma/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
Mismatch repair (MMR) corrects replicative errors and minimizes DNA damage that occurs frequently in microsatellites. MMR deficiency is manifested as microsatellite instability (MSI), which contributes to hypermutability and cancer pathogenesis. Genomic instability, including MSI and chromosomal instability, appears to be responsible for the carcinogenesis of arsenic and cadmium, common contaminants in our environment. However, few studies have addressed arsenic- or cadmium-induced MSI, especially its potential link with arsenic- or cadmium-generated oxidative stress, due to the lack of quantifiable MSI assays and cost-effective animal models. Here, using a dual-fluorescent reporter, we demonstrate that sub-lethal doses of cadmium or arsenite, but not arsenate, increased the MSI frequency in human colorectal cancer cells. Arsenite- and cadmium-induced MSI occurred concomitantly with increased levels of reactive species and oxidative DNA damage, and with decreased levels of MMR proteins. However, N-acetyl-l-cysteine (NAC) suppressed arsenite- and cadmium-induced MSI and oxidative stress while restoring the levels of MMR proteins in the cells. Similarly, MSI was induced separately by arsenite and cadmium, and suppressed by NAC, in zebrafish in a fluorescinated PCR-based assay with newly-developed microsatellite markers and inter-segmental comparisons. Of five selected antioxidants examined, differential effects were exerted on the MSI induction and cytotoxicity of both arsenite and cadmium. Compared to MMR-proficient cells, MMR-deficient cells were more resistant to arsenic-mediated and cadmium-mediated cytotoxicity. Our findings demonstrate a novel linkage between arsenite-generated and cadmium-generated oxidative stress and MSI induction. Our findings also caution that antioxidants must be individually validated before being used for preventing arsenite- and cadmium-induced MSI that is associated with cancer development.
Assuntos
Arsenitos/toxicidade , Cloreto de Cádmio/toxicidade , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , DNA/genética , Instabilidade de Microssatélites/efeitos dos fármacos , Compostos de Sódio/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Arsenitos/antagonistas & inibidores , Cloreto de Cádmio/antagonistas & inibidores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Dano ao DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HCT116 , Humanos , Repetições de Microssatélites/efeitos dos fármacos , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sódio/antagonistas & inibidores , Peixe-ZebraRESUMO
Multidrug resistance (MDR) to chemotherapeutic drugs is a formidable barrier to the success of cancer chemotherapy. Expressions of ATP-binding cassette (ABC) transporters contribute to clinical MDR phenotype. In this study, we found that afatinib, a small molecule tyrosine kinase inhibitor (TKI) targeting EGFR, HER-2 and HER-4, reversed the chemoresistance mediated by ABCG2 in vitro, but had no effect on that mediated by multidrug resistance protein ABCB1 and ABCC1. In addition, afatinib, in combination with topotecan, significantly inhibited the growth of ABCG2- overexpressing cell xenograft tumors in vivo. Mechanistic investigations exhibited that afatinib significantly inhibited ATPase activity of ABCG2 and downregulated expression level of ABCG2, which resulted in the suppression of efflux activity of ABCG2 in parallel to the increase of intracellular accumulation of ABCG2 substrate anticancer agents. Taken together, our findings may provide a new and useful combinational therapeutic strategy of afatinib with chemotherapeutical drug for the patients with ABCG2 overexpressing cancer cells.
Assuntos
Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Experimentais/tratamento farmacológico , Quinazolinas/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Afatinib , Animais , Western Blotting , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Topotecan/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A pot experiment was conducted to investigate the effects of high temperature and humidity stress [(40 +/- 2) degrees C/(30 +/- 2) degrees C, RH (95 +/- 5)%/(70 +/- 5)%, 10 h/14 h (day/night)] at the physiological maturity stage of two spring soybean cultivars (Xiangdou No. 3 and Ningzhen No. 1) on seed vigor indices, main nutritional components and coat anatomical structure. High temperature and humidity stress were found to cause the decrease of seed viability, germination potential, and germination percentage as well as the dehydrogenase and acid phosphatase activities, but increased the seed cell membrane permeability as well as H+, soluble sugar and leucine levels in the seed soaking liquid of each cultivar. Moreover, the stress led to irregular changes of seed oil and protein contents and alteration of anatomical structure of episperm and hilum in the two cultivars. A shortterm stress (less than 5 h) had no significant impact on seed vigor, but a long-term one (more than 48 h) caused rapid decrease of seed vigor indices. Xiangdou No. 3 showed less decreases in seed germination potential and enzyme activities, and less increase in extravasation content in the seed soaking liquid, had compact seed coat and intact hilum, suggesting it was more resistant to high temperature and humidity stress.