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To investigate the clinical effects and application value of self-made disseminating and descending breathing exercises on home rehabilitation of patients with stable chronic obstructive pulmonary disease (COPD). Seeking to generate concepts for creating novel, convenient, and efficient COPD prognosis rehabilitation exercises aimed at enhancing the well-being and rehabilitation confidence of both COPD patients and their families. A total of 70 COPD patients admitted to our outpatient department from July 2019 to September 2021 were randomly divided into the exercise group (n = 35) and the control group (n = 35). The control group received routine breathing training, while the exercise group was treated with self-made disseminating and descending breathing exercises. The respiratory function, including pulmonary function (FVC, FEV1, FEV1/FVC) and respiratory muscle strength (MIP, MEP), exercise tolerance (6-min walking distance, 6MWT), Modified Medical Research Council Dyspnea Scale (mMRC, Borg), COPD quality of life score (CAT, SGRQ), anxiety and depression scores (HAMA, HAMD) were compared between the two groups after 12-week exercise. After 12-week training, the FEV1, MIP, and MEP in the exercise group were significantly higher than those in the control group (p < 0.001), and the 6MWT was significantly increased in the exercise group compared to the control group (p < 0.001); while the mMRC, Borg score, the scores of CAT, SGRQ, HAMA, and HAMD were found significantly lower than those in the control group (p < 0.001). The self-made disseminating and descending breathing exercises can improve respiratory function and reduce symptoms of dyspnea in COPD patients, while enhancing exercise tolerance and relieving anxiety and depression, and are worthy of clinical application.
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Exercícios Respiratórios , Tolerância ao Exercício , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Exercícios Respiratórios/métodos , Idoso , Pessoa de Meia-Idade , Dispneia/etiologia , Dispneia/reabilitação , Força Muscular , Depressão , Ansiedade/etiologia , Músculos Respiratórios/fisiopatologia , Teste de Caminhada , Volume Expiratório ForçadoRESUMO
Phenethyl isothiocyanate (PEITC), a natural product, exists in biological activities, including anticancer activity in many human cancer cells. No information shows that PEITC affects DNA damage in human retinoblastoma (RB) cells in vitro. In this study, the aim of experiments was to determine whether PEITC decreased total viable cell number or not by inducing protein expressions involved in DNA damage and repair in Y79 RB cells in vitro. Total cell viability was measured by PI exclusion assay, and PEITC reduced the total Y79 viable cell numbers in a dose-dependent manner. DNA condensation and DNA impairment were conducted by DAPI staining and comet assays, respectively, in Y79 cells. The findings show that PEITC induced DNA condensation dose-dependently based on the brighter fluorescence of cell nuclei stained by DAPI staining. PEITC-induced DNA damage showed a more extended DNA migration smears than that of the control, which was performed by a comet assay. Western blotting was performed to measure the protein expressions involved in DNA damage and repair, which showed that PEITC at 2.5-10 µM increased NRF2, HO-1, SOD (Mn), and catalase; however, it decreased SOD (Cu/Zn) except 10 µM PEITC treatment, and decreased glutathione, which were associated with oxidative stress. Furthermore, PEITC increased DNA-PK, MDC1, H2A.XpSer139, ATMpSer1981, p53, p53pSer15, PARP, HSP70, and HSP90, but decreased TOPIIα, TOPIIß, and MDM2pSer166 that were associated with DNA damage and repair mechanism in Y79 cells. The examination from confocal laser microscopy shows that PEITC increased H2A.XpSer139 and p53pSer15, and decreased glutathione and TOPIIα in Y79 cells. In conclusion, the cytotoxic effects of PEITC on reducing the number of viable cells may be due to the induction of DNA damage and the alteration of DNA repair proteins in Y79 cells in vitro.
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BACKGROUND: The development of emergency department (ED) triage systems remains challenging in accurately differentiating patients with acute abdominal pain (AAP) who are critical and urgent for surgery due to subjectivity and limitations. We use machine learning models to predict emergency surgical abdominal pain patients in triage, and then compare their performance with conventional Logistic regression models. METHODS: Using 38 214 patients presenting with acute abdominal pain at Zhongnan Hospital of Wuhan University between March 1, 2014, and March 1, 2022, we identified all adult patients (aged ≥18 years). We utilized routinely available triage data in electronic medical records as predictors, including structured data (eg, triage vital signs, gender, and age) and unstructured data (chief complaints and physical examinations in free-text format). The primary outcome measure was whether emergency surgery was performed. The dataset was randomly sampled, with 80% assigned to the training set and 20% to the test set. We developed 5 machine learning models: Light Gradient Boosting Machine (Light GBM), eXtreme Gradient Boosting (XGBoost), Deep Neural Network (DNN), and Random Forest (RF). Logistic regression (LR) served as the reference model. Model performance was calculated for each model, including the area under the receiver-work characteristic curve (AUC) and net benefit (decision curve), as well as the confusion matrix. RESULTS: Of all the 38 214 acute abdominal pain patients, 4208 underwent emergency abdominal surgery while 34 006 received non-surgical treatment. In the surgery outcome prediction, all 4 machine learning models outperformed the reference model (eg, AUC, 0.899 [95%CI 0.891-0.903] in the Light GBM vs. 0.885 [95%CI 0.876-0.891] in the reference model), Similarly, most machine learning models exhibited significant improvements in net reclassification compared to the reference model (eg, NRIs of 0.0812[95%CI, 0.055-0.1105] in the XGBoost), with the exception of the RF model. Decision curve analysis shows that across the entire range of thresholds, the net benefits of the XGBoost and the Light GBM models were higher than the reference model. In particular, the Light GBM model performed well in predicting the need for emergency abdominal surgery with higher sensitivity, specificity, and accuracy. CONCLUSIONS: Machine learning models have demonstrated superior performance in predicting emergency abdominal pain surgery compared to traditional models. Modern machine learning improves clinical triage decisions and ensures that critically needy patients receive priority for emergency resources and timely, effective treatment.
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BACKGROUND AND PURPOSE: Cerebrovascular events during thrombolysis in cardiac arrest (CA) caused by pulmonary embolism (PE) is a life-threatening condition. However, the balance between cerebrovascular events and thrombolytic therapy in PE-induced CA remains a great challenge. METHODS: In this study, we reported three unique cases regarding main concerns surrounding cerebrovascular events in thrombolytic therapy in PE-induced CA. RESULTS: The patient in the case 1 treated with thrombolysis during CPR and finally discharged neurologically intact. The patient in the case 2 received delayed thrombolysis and died eventually. The patient in the case 3 was contraindicated to thrombolysis due to the complication of subarachioid hemorrahage and died within days. CONCLUSIONS: Our case series highlights three proposed approaches to consider before administering thrombolysis as a treatment option in PE-induced CA patients: (1) prolonging the resuscitation, (2) administering thrombolysis promptly, and (3) ruling out cerebrovascular events.
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Fibrinolíticos , Parada Cardíaca , Embolia Pulmonar , Terapia Trombolítica , Humanos , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Terapia Trombolítica/efeitos adversos , Masculino , Parada Cardíaca/diagnóstico , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Fibrinolíticos/efeitos adversos , Fibrinolíticos/administração & dosagem , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso , Evolução Fatal , Feminino , Reanimação Cardiopulmonar , Fatores de Risco , Tempo para o Tratamento , Fatores de Tempo , Tomada de Decisão ClínicaRESUMO
BACKGROUND: Lymphedema is a debilitating condition that significantly affects quality of life due to its chronic nature and visible symptoms. Lymphaticovenous anastomosis (LVA) has emerged as a promising surgical intervention, yet its effects on body image and spiritual health alongside physical symptoms have not been thoroughly examined. This study evaluates the efficacy of LVA in improving symptoms, quality of life (QOL), body image, and spiritual well-being in lymphedema patients. METHODS: A prospective cohort study was conducted at Kaohsiung Chang Gung Memorial Hospital, Taiwan, involving 44 patients with lymphedema undergoing LVA surgery. Evaluations were made pre-surgery, one month post-surgery, and six months post-surgery using the 36-Item Short Form Health Survey (SF-36), Multidimensional Body-Self Relations Questionnaire-Appearance Scales (MBSRQ-AS), and a spiritual health scale. Statistical analysis was performed using one-way repeated measures ANOVA. RESULTS: Significant improvements were observed in lymphedema symptoms and QOL measures at six months post-operation. SF-36 results showed enhanced scores in nearly all domains, particularly in physical functioning and role-physical. The appearance orientation scores from the MBSRQ-AS significantly increased, indicating improved perceptions in some dimensions of body image. CONCLUSIONS: LVA surgery significantly enhances physical and psychological outcomes in patients with lymphedema, with marked improvements in symptoms, QOL, and body image perceptions. The findings suggest that while LVA is effective in addressing the physical and psychological aspects of lymphedema, it does not impact spiritual dimensions. This underscores the need for holistic approaches in the management of lymphedema to address all facets of patient well-being.
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Transition metals are promising catalysts for environmental remediation. However, their low reactivity, poor stability and weak reusability largely limit practical applications. Herein, we report that the electron-rich dissolved black carbon (DBC) incorporated into the nanoscale zero-valent copper (nZVCu) can boost intrinsic reactivity, structural stability and cyclic reusability for superior peroxymonosulfate (PMS) activation and pollutant degradation. A series of refractory pollutants can be effectively removed on the DBC/nZVCu, in comparison with the nZVCu reference. Hydroxyl radical (â§OH) is identified as the dominant reactive oxygen species by electron spin resonance (ESR) and chemical quenching tests, mediated by the metastable Cu(III) as the key reactive intermediate. The electron-rich DBC protects nanoscale Cu from oxidative corrosion to slow down the surface formation of inert CuO layer, rendered by the thermodynamically and dynamically capacitive regulation of corrosive electron transfer from metallic core. By this refining way, the conducive DBC improves the neighboring utilization of reactive electron during metal corrosion, oxidant activation, radical generation and pollutant degradation in Fenton-like catalysis. Our findings suggest that the ubiquitous DBC can be an efficient chelating agent to refine transition metals by serving as the surface deactivator and electron mediator, and take new insights into their environmental and agricultural geochemistry.
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CLEC6A, (C-type lectin domain family 6, member A), plays a prominent role in regulating innate immunity and adaptive immunity. CLEC6A has shown great potential as a target for cancer immunotherapy. This study aims to explore the prognostic value of CLEC6A, and analyze the relationship associated with the common hematological parameters in breast cancer patients. We performed a retrospective analysis on 183 breast cancer patients data in hospital information system from January 2013 to December 2015. The expression of CLEC6A was recorded via semiquantitative immunohistochemistry in breast cancer. The association between expression of CLEC6A and relative parameters were performed by Chi-square test and Fisher's exact test. Kaplan-Meier assay and Log-rank test were performed to evaluate the survival time. The Cox proportional hazards regression analysis was applied to identify prognostic factors. Nomograms were conducted to predict 1-, 3-, and 5-year disease free survival (DFS) and overall survival (OS) for breast cancer, which could be a good reference in clinical practice. The nomogram model was estimated by calibration curve analysis for its function of discrimination. The accuracy and benefit of the nomogram model were appraised by comparing it to only CLEC6A via decision curve analysis (DCA). The prediction accuracy of CLEC6A was also determined by time-dependent receiver operating characteristics (TDROC) curves, and the area under the curve (AUC) for different survival time. There were 94 cases in the CLEC6A low-expression group and 89 cases in CLEC6A high-expression group. Compared to CLEC6A low-expression group, the CLEC6A high-expression group had better survival (DFS: 56.95 vs. 70.81 months, P = 0.0078 and OS: 67.98 vs. 79.05 months, P = 0.0089). The CLEC6A was a potential prognostic factor in multivariate analysis (DFS: P = 0.023, hazard ratio (HR): 0.454, 95 % confidence interval (CI): 0.229-0.898; OS: P = 0.020, HR: 0.504, 95 %CI: 0.284-0.897). The nomogram in accordance with these potential prognostic factors was constructed to predict survival and the calibration curve analysis had indicated that the predicted line was well-matched with reference line in 1-, 3-, and 5-year DFS and OS category. The 1-, 3-, and 5-year DCA curves have revealed that nomogram model yielded larger net benefits than CLEC6A alone. Finally, the TDROC curve indicated that CLEC6A could better predict 1-year DFS and OS than others. Furthermore, we combined these potential independent prognostic factors to analyze the relationship among these hematologic index and oxidative stress indicators, and indicated that higher CLEC6A level, higher CO2 level or low CHOL level or high HDL-CHO level would have survived longer and better prognosis. In breast cancer, high expression of CLEC6A can independently predict better survival. Our nomogram consisted of CLEC6A and other indicators has good predictive performance and can facilitate clinical decision-making.
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Biomarcadores Tumorais , Neoplasias da Mama , Lectinas Tipo C , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Neoplasias da Mama/imunologia , Pessoa de Meia-Idade , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Prognóstico , Estudos Retrospectivos , Adulto , Idoso , Nomogramas , Estimativa de Kaplan-Meier , Intervalo Livre de DoençaRESUMO
Thymol has efficient bactericidal activity against a variety of pathogenic bacteria, but the bactericidal mechanism against Vibrio parahemolyticus (V. parahemolyticus) has rarely been reported. In the current study, we investigated the bactericidal mechanism of thymol against V. parahemolyticus. The Results revealed that 150 µg/mL of thymol had 99.9% bactericidal activity on V. parahemolyticus. Intracellular bursts of reactive oxygen species (ROS), Fe2+accumulation, lipid peroxidation, and DNA breakage were checked by cell staining. The exogenous addition of H2O2 and catalase promoted and alleviated thymol-induced cell death to a certain extent, respectively, and the addition of the ferroptosis inhibitor Liproxstatin-1 also alleviated thymol-induced cell death, confirming that thymol induced Fenton-reaction-dependent ferroptosis in V. parahemolyticus. Proteomic analysis revealed that relevant proteins involved in ROS production, lipid peroxidation accumulation, and DNA repair were significantly upregulated after thymol treatment. Molecular docking revealed two potential binding sites (amino acids 46H and 42F) between thymol and ferritin, and thymol could promote the release of Fe2+ from ferritin proteins through in vitro interactions analyzed. Therefore, we hypothesized that ferritin as a potential target may mediate thymol-induced ferroptosis in V. parahemolyticus. This study provides new ideas for the development of natural inhibitors for controlling V. parahemolyticus in aquatic products.
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Antibacterianos , Ferroptose , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Timol , Vibrio parahaemolyticus , Ferroptose/efeitos dos fármacos , Timol/farmacologia , Timol/química , Espécies Reativas de Oxigênio/metabolismo , Vibrio parahaemolyticus/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Ferro/metabolismo , Simulação de Acoplamento Molecular , Ferritinas/genética , Ferritinas/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genéticaRESUMO
Electroencephalographic (EEG) source imaging (ESI) is a powerful method for studying brain functions and surgical resection of epileptic foci. However, accurately estimating the location and extent of brain sources remains challenging due to noise and background interference in EEG signals. To reconstruct extended brain sources, we propose a new ESI method called Variation Sparse Source Imaging based on Generalized Gaussian Distribution (VSSI-GGD). VSSI-GGD uses the generalized Gaussian prior as a sparse constraint on the spatial variation domain and embeds it into the Bayesian framework for source estimation. Using a variational technique, we approximate the intractable true posterior with a Gaussian density. Through convex analysis, the Bayesian inference problem is transformed entirely into a series of regularized L2p -norm ( ) optimization problems, which are efficiently solved with the ADMM algorithm. Imaging results of numerical simulations and human experimental dataset analysis reveal the superior performance of VSSI-GGD, which provides higher spatial resolution with clear boundaries compared to benchmark algorithms. VSSI-GGD can potentially serve as an effective and robust spatiotemporal EEG source imaging method. The source code of VSSI-GGD is available at https://github.com/Mashirops/VSSI-GGD.git.
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Encéfalo , Eletroencefalografia , Humanos , Teorema de Bayes , Distribuição Normal , Eletroencefalografia/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Algoritmos , Magnetoencefalografia/métodosRESUMO
This study aimed to investigate the characteristic choroidal changes in patients with diabetic retinopathy and identify factors affecting choroidal thickness (CTh), choroidal vascular index (CVI), and choriocapillaris flow. We retrospectively analyzed 79 eyes of 48 patients with diabetes between August 2021 and February 2022. We collected laboratory data, including HbA1c, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) levels. Optical coherence tomography images of the foveal avascular zone, retinal vascular density, choroidal flow, retinal thickness, CTh, and CVI were analyzed. Possible determining factors affecting CTh, CVI, and choriocapillaris flow were analyzed using nonparametric multivariate analysis. LDL (p < 0.001) positively correlated with CTh, whereas CVI (p = 0.007) was negatively correlated with CTh in diabetic patients with diabetes. We also identified a negative correlation between choriocapillaris flow and deep parafoveal retinal vessel density in patients with low-grade diabetic retinopathy (DR), which diminished in those with more advanced DR. Our study provides further information on the changes in choroidal structure and blood flow in patients with diabetes.
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In this study, the ecological risk assessment of PAHs pollution, the existing S-T model was improved and applied to this PAHs pollution assessment in surface sediment in Lake Chaohu. The potential sources and contributions of PAHs in the surface sediment were estimated by molecular diagnostic ratio (MDR) and positive matrix factorization (PMF). The results showed that the average concentration of 16 priority PAHs in the surface sediment was 718.16 ng/g in 2009 and 334.67 ng/g in 2020. In 2020, PAHs concentration has decreased compared to 2009 and the dominant composition has changed from high- to low-molecular-weight PAHs. The estimated PAHs mass inventory of the top 2 cm surface sediment was 2712 tons in 2009 and 1263 tons in 2020. Ecosystem risk assessment by improved S-T models suggested that the overall ecosystem risk of the studied regions was acceptable.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Ecossistema , Monitoramento Ambiental , Lagos/análise , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Medição de Risco , ChinaRESUMO
Dynamic gravity field measurement based on the cold atom absolute gravity measurement system has important applications in geological exploration, gravity field mapping and other fields. The inertial stabilized platform is the key component of the dynamic cold atom absolute gravity measurement system, which can isolate the interference of carrier angle motion and keep the atomic gravimeter probe in the horizontal attitude during the measurement process. In this paper, according to the dynamic measurement requirements of atomic gravimeter, a high-precision two-axis inertial stabilized platform system is designed. The relationship between attitude angle and gravity measurement error is analyzed, and the stability of the system is enhanced by lead-lag method. Then the static vertical vibration power spectrum of the platform is measured to consider its influence on dynamic gravity measurement. Finally, a dynamic gravity test experiment was conducted in the Yellow Sea to verify the attitude control accuracy of the platform, and the attitude data of the platform under different heading were evaluated. The attitude standard deviation of the platform was better than 4 × 10-5 rad, and the absolute gravity standard deviation of the linear round-trip measurement reached 1.49 mGal. The experimental data show that the inertial stabilized platform can meet the dynamic measurement requirements of the cold atom gravimeter.
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Irinotecan (IRI), an anticancer drug to treat colon cancer patients, causes cytotoxic effects on normal cells. Phenethyl isothiocyanate (PEITC), rich in common cruciferous plants, has anticancer activities (induction of cell apoptosis) in many human cancer cells, including colon cancer cells. However, the anticancer effects of IRI combined with PEITC on human colon cancer cells in vitro were unavailable. Herein, the aim of this study is to focus on the apoptotic effects of the combination of IRI and PEITC on human colon cancer HCT 116 cells in vitro. Propidium iodide (PI) exclusion and Annexin V/PI staining assays showed that IRI combined with PEITC decreased viable cell number and induced higher cell apoptosis than that of IRI or PEITC only in HCT 116 cells. Moreover, combined treatment induced higher levels of reactive oxygen species (ROS) and Ca2+ than that of IRI or PEITC only. Cells pre-treated with N-acetyl-l-cysteine (scavenger of ROS) and then treated with IRI, PEITC, or IRI combined with PEITC showed increased viable cell numbers than that of IRI or PEITC only. IRI combined with PEITC increased higher caspase-3, -8, and -9 activities than that of IRI or PEITC only by flow cytometer assay. IRI combined with PEITC induced higher levels of ER stress-, mitochondria-, and caspase-associated proteins than that of IRI or PEITC treatment only in HCT 116 cells. Based on these observations, PEITC potentiates IRI anticancer activity by promoting cell apoptosis in the human colon HCT 116 cells. Thus, PEITC may be a potential enhancer for IRI in humans as an anticolon cancer drug in the future.
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Apoptose , Neoplasias do Colo , Humanos , Irinotecano/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células HCT116 , Linhagem Celular Tumoral , Isotiocianatos/farmacologia , Neoplasias do Colo/tratamento farmacológicoRESUMO
Nanodrug delivery systems have demonstrated a great potential for tumor therapy with the development of nanotechnology. Nonetheless, traditional drug delivery systems are faced with issues such as complex synthetic procedures, low reproducibility, nonspecific distribution, impenetrability of biological barrier, systemic toxicity, etc. In recent years, phage-based nanoplatforms have attracted increasing attention in tumor treatment for their regular structure, fantastic carrying property, high transduction efficiency and biosafety. Notably, therapeutic or targeting peptides can be expressed on the surface of the phages through phage display technology, enabling the phage vectors to possess multifunctions. As a result, the drug delivery efficiency on tumor will be vastly improved, thereby enhancing the therapeutic efficacy while reducing the side effects on normal tissues. Moreover, phages can overcome the hindrance of biofilm barrier to elicit antitumor effects, which exhibit great advantages compared with traditional synthetic drug delivery systems. Herein, this review not only summarizes the structure and biology of the phages, but also presents their potential as prominent nanoplatforms against tumor in different pathways to inspire the development of effective nanomedicine.
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Bacteriófagos , Neoplasias , Humanos , Reprodutibilidade dos Testes , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Peptídeos/químicaRESUMO
Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair-associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC-induced cytotoxic effects on human gastric cancer in AGS and SNU-1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU-1 cells in a dose-dependently. AITC induced DNA condensation and damage in a dose-dependently which based on the cell nuclei was stained by 4', 6-diamidino-2-phenylindole present in AGS and SNU-1 cells. DNA damage and repair associated proteins expression in AGS and SNU-1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU-1 cells are increased HO-1. AITC increased DNA-dependent protein kinase (DNA-PK), phosphorylation of gamma H2A histone family member X on Ser139 (γH2AXpSer139 ), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA-PK, mediator of DNA damage checkpoint protein 1 (MDC1), γH2AXpSer139 , topoisomerase II alpha (TOPIIα), topoisomerase II beta (TOPIIß), HSP90, and heat shock protein 70 (HSP70) in SNU-1 cells. AITC increased p53, p53pSer15 , and p21 but decreased murine double minute 2 (MDM2)pSer166 and O6 -methylguanine-DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad3 -related protein (ATR)pSer428 , checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU-1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro.
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Neoplasias Gástricas , Proteína Supressora de Tumor p53 , Humanos , Animais , Camundongos , Proteína Supressora de Tumor p53/genética , Dano ao DNA , Isotiocianatos/farmacologia , Reparo do DNA , DNA , Linhagem Celular TumoralRESUMO
SLC7A11 is a unit of the glutamate cystine antiporter Xc- system. It functions to import cystine for glutathione biosynthesis and maintains the redox balance in cells. Sorafenib inhibits the transporter activity of SLC7A11. The use of sorafenib has been approved in the treatment of multiple cancers. However, at present, our understanding of the mechanism of SLC7A11 and sorafenib in nasopharyngeal carcinoma (NPC) remains limited. We found that the expression of SLC7A11 was upregulated in NPC. A high SLC7A11 expression was associated with poor prognosis, metastasis, and an advanced T stage, which can be used as an independent prognostic indicator of NPC. In vitro, we observed that NPC cells relied on cystine for survival. Targeting SLC7A11 resulted in glutathione biosynthesis limitation, intracellular reactive oxygen species accumulation, lipid peroxides, ferroptosis, and apoptosis. Meanwhile, it altered mitogen activated protein kinase pathway, including p38 activation but ERK inhibition in NPC. This limited the proliferation of NPC cells. Sorafenib inhibited the proliferation and induced the death of NPC cells in vivo. In conclusion, SLC7A11 plays an important role in the occurrence and progression of NPC and may be a novel target for NPC treatment.
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Ferroptose , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Sorafenibe/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Cistina/metabolismo , Apoptose , Glutationa/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismoRESUMO
Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine 4 (CXCR4) have been demonstrated to play critical roles in diabetic retinopathy (DR). This study investigated whether single-nucleotide polymorphisms (SNPs) of SDF-1 and its receptor CXCR4 are correlated with diabetic retinopathy (DR). Three SDF-1 SNPs, namely, rs1801157 (G/A), rs2297630 (G/A), and rs266085 (T/C), and two CXCR4 SNPs, namely, rs2228014 (C/T) and rs6430612 (C/T), were chosen and genotyped via the TaqMan allelic discrimination for 454 non-DR subjects and 276 DR individuals. Our results revealed that subjects carrying SDF-1 SNP rs2297630 GA (AOR: 2.962, 95% CI: 1.279-6.861, p = 0.011) and SDF-1 SNP rs2297630 GA + AA (AOR: 3.095, 95% CI: 1.394-6.872, p = 0.006) had significantly higher risk in the non-proliferative diabetic retinopathy (NPDR) groups than in the non-DR group. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal revealed that SDF-1 SNP rs2297630 GA and AA genotypic variants have higher SDF-1 expression than the GG wild-type alleles (p = 0.000016). In conclusion, our findings revealed that SDF-1 SNP rs2297630 was associated with NPDR.
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BACKGROUND: With the withdrawal of paraquat from the market, diquat is widely used, so the treatment of diquat poisoning has become one of the focuses of emergency poisoning diagnosis and treatment. CASE SUMMARY: We studied the case of a 17-year-old male patient who drank 200 mL (20 g/100 mL) of diquat solution two hours before arriving at the hospital. Despite the use of treatments such as gastric lavage, hemoperfusion, continuous hemodialysis, glucocorticoids, and organ support, the patient's condition rapidly progressed to multiorgan failure, and he died 23.5 h after admission. CONCLUSION: We summarized the clinical characteristics and treatment strategies of diquat poisoning through this case and performed a literature review to provide a basis and direction for clinical treatment.
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The glucagon-like peptide 1 (GLP-1) agonist showed anti-hyperglycemic and anti-inflammatory effects, which may retard the risk of external eye disease. The protective effect of GLP-1 agonist and dry eye disease (DED) was found, while the relationship between GLP-1 agonist and other corneal diseases was not clear. Herein, we aim to evaluate the association between the usage of GLP-1 agonists and the development of the following external eye disease in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan was conducted. The T2DM patients were divided into those with GLP-1 treatment and those without GLP-1 treatment and matched with a 1:2 ratio. The main outcomes were the development of dry eye disease (DED), superficial keratitis, and infectious keratitis. The Cox proportional hazard regression was adopted to produce the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) of external eye diseases between groups. There were 115, 54, and 11 episodes of DED, superficial keratitis, and infectious keratitis in the GLP-1 group. Another 280, 168, and 31 events of DED, superficial keratitis, and infectious keratitis were recorded in the control group. The GLP-1 group demonstrated a significantly lower incidence of DED (aHR: 0.853, 95% CI: 0.668-0.989, p = 0.0356) and superficial keratitis (aHR: 0.670, 95% CI: 0.475-0.945, p = 0.0107) compared to the control group. In the subgroup analyses, the correlation of GLP-1 agonist and DED development was more prominent in patients younger than 60 years old (p = 0.0018). In conclusion, the GLP-1 agonist treatments are significantly associated with a lower incidence of subsequent DED and superficial keratitis, while the relationship was not significant between GLP-1 agonist usage and infectious keratitis.
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OBJECTIVES: Our objective is to develop a prediction tool to predict the death after in-hospital cardiac arrest (IHCA). DESIGN: We conducted a retrospective double-centre observational study of IHCA patients from January 2015 to December 2021. Data including prearrest diagnosis, clinical features of the IHCA and laboratory results after admission were collected and analysed. Logistic regression analysis was used for multivariate analyses to identify the risk factors for death. A nomogram was formulated and internally evaluated by the boot validation and the area under the curve (AUC). Performance of the nomogram was further accessed by Kaplan-Meier survival curves for patients who survived the initial IHCA. SETTING: Intensive care unit, Tongji Hospital, China. PARTICIPANTS: Adult patients (≥18 years) with IHCA after admission. Pregnant women, patients with 'do not resuscitation' order and patients treated with extracorporeal membrane oxygenation were excluded. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the death after IHCA. RESULTS: Patients (n=561) were divided into two groups: non-sustained return of spontaneous circulation (ROSC) group (n=241) and sustained ROSC group (n=320). Significant differences were found in sex (p=0.006), cardiopulmonary resuscitation (CPR) duration (p<0.001), total duration of CPR (p=0.014), rearrest (p<0.001) and length of stay (p=0.004) between two groups. Multivariate analysis identified that rearrest, duration of CPR and length of stay were independently associated with death. The nomogram including these three factors was well validated using boot calibration plot and exhibited excellent discriminative ability (AUC 0.88, 95% CI 0.83 to 0.93). The tertiles of patients in sustained ROSC group stratified by anticipated probability of death revealed significantly different survival rate (p<0.001). CONCLUSIONS: Our proposed nomogram based on these three factors is a simple, robust prediction model to accurately predict the death after IHCA.