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Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (Ka) for the LDH-rutin system was 2.692 ± 0.015 × 104 M-1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel ß-sheet, and ß-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin.
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L-Lactato Desidrogenase , Rutina , Rutina/química , Rutina/farmacologia , Rutina/metabolismo , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/química , Humanos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Simulação por Computador , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Magnetic resonance vessel wall imaging (MR-VWI) is an emerging imaging technology used to assess the progressive risk of unruptured intracranial aneurysms (UIAs). Unlike the standard evaluation model, MR-VWI is still debatable. This study aims to further define the potential relationship between aneurysm wall enhancement (AWE) and aneurysm stability. Using "intracranial aneurysm", "magnetic resonance", and "enhancement" as keywords, relevant studies were systematically searched in PubMed, Embase, and Cochrane, and the qualified studies were enrolled for further analysis. There were 13 case-control studies, 4 cohort studies, and 2,678 cases of intracranial aneurysms included in the meta-analysis. It was shown that AWE was correlated with intracranial aneurysm rupture (OR = 35.90, 95% CI: 15.58 to 82.75, p < 0.001), growth (OR = 6.69, 95% CI: 2.69 to 16.63, p < 0.001), and presence of symptoms (OR = 14.46, 95% CI: 9.07 to 23.05, p < 0.001). This finding had a high diagnostic value, but the correlation was probably not independent of aneurysm size. The pooled relative risks of the follow-up studies revealed that the risk of UIA progression was approximately 3.33 times higher with AWE than without AWE (RR = 3.33, 95% CI: 2.33 to 4.78, p < 0.001). In addition, the pooled results demonstrated that quantitative indices of VWI enhancement were equally linked with aneurysm stability (OR = 19.61, 95% CI: 10.63 to 36.17, p < 0.001). AWE is an effective imaging method to assess the stability of UIAs, and it can be a marker for the prophylactic treatment of small unruptured intracranial aneurysms in the future, which remains to be validated by prospective studies with large samples.
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Aneurisma Intracraniano , Estudos Observacionais como Assunto , Aneurisma Intracraniano/diagnóstico por imagem , Humanos , Aneurisma Roto/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Estrogen (E2) is the main contributor to the progression of endometrial cancer (EC). The long noncoding RNA HOX antisense intergenic RNA (HOTAIR) is emerging as a new regulator in several cancer types. This study aimed to investigate the role of HOTAIR in EC development and identify the underlying molecular mechanisms. METHODS: HOTAIR expression levels in human EC tissues and the corresponding adjacent tissues and human EC Ishikawa cells were determined by quantitative PCR. Ishikawa cells were treated with E2 or estrogen receptor (ER) inhibitor ICI182780, transfected with siHOTAIR oligo, or infected with lentivirus expressing shHOTAIR/shNC, alone or in combinations. The protein expression of polycomb repressive complex 2 (PRC2) was evaluated by western blotting, and cell migration was measured by transwell assays. A xenograft tumorigenic model was established by inoculating control or stable shHOTAIR-infected Ishikawa cells into nude mice and implanting 17ß-estradiol release pellets. RESULTS: HOTAIR expression was significantly elevated in human EC tissues. E2 exposure markedly increased HOTAIR levels in Ishikawa cells. Notably, E2 increased the protein expression of PRC2 and promoted EC cell migration, which were dependent on HOTAIR expression, as HOTAIR knockdown abolished these effects of E2. Similarly, E2 promoted the in vivo proliferation of grafted Ishikawa cells via upregulated HOTAIR expression in nude mice. CONCLUSIONS: Human EC tissues highly express HOTAIR, and E2-induced EC progression depends on HOTAIR expression. This work suggests that the E2-HOTAIR axis is a potential therapeutic target in EC therapy.
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Neoplasias do Endométrio , RNA Longo não Codificante , Animais , Feminino , Humanos , Camundongos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Estrogênios/farmacologia , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , RNA Longo não Codificante/genéticaRESUMO
Brain oscillations have gained great attention in neuroscience during recent decades as functional building blocks of cognitive-sensory processes. Research has shown that oscillations in "alpha," "beta," "gamma," "delta," and "theta" frequency windows are highly modified in brain pathology, including in patients with cognitive impairment like bipolar disorder (BD). The study of changes in brain oscillations can provide fundamental knowledge for exploring neurophysiological biomarkers in cognitive impairment. The present article reviews findings from the role and molecular basis of abnormal neural oscillation and synchronization in the symptoms of patients with BD. An overview of the results clearly demonstrates that, in cognitive-sensory processes, resting and evoked/event-related electroencephalogram (EEG) spectra in the delta, theta, alpha, beta, and gamma bands are abnormally changed in patients with BD showing psychotic features. Abnormal oscillations have been found to be associated with several neural dysfunctions and abnormalities contributing to BD, including abnormal GABAergic neurotransmission signaling, hippocampal cell discharge, abnormal hippocampal neurogenesis, impaired cadherin and synaptic contact-based cell adhesion processes, extended lateral ventricles, decreased prefrontal cortical gray matter, and decreased hippocampal volume. Mechanistically, impairment in calcium voltage-gated channel subunit alpha1 I, neurotrophic tyrosine receptor kinase proteins, genes involved in brain neurogenesis and synaptogenesis like WNT3 and ACTG2, genes involved in the cell adhesion process like CDH12 and DISC1, and gamma-aminobutyric acid (GABA) signaling have been reported as the main molecular contributors to the abnormalities in resting-state low-frequency oscillations in BD patients. Findings also showed the association of impaired synaptic connections and disrupted membrane potential with abnormal beta/gamma oscillatory activity in patients with BD. Of note, the synaptic GABA neurotransmitter has been found to be a fundamental requirement for the occurrence of long-distance synchronous gamma oscillations necessary for coordinating the activity of neural networks between various brain regions.
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Transtorno Bipolar , Biomarcadores , Encéfalo/patologia , Caderinas , Cálcio , Cognição , Eletroencefalografia , Humanos , Ácido gama-AminobutíricoRESUMO
A study was carried out on the effectiveness of bioretention systems to abate stormwater using computer simulation. The hydrologic performance was simulated for two bioretention cells using HYDRUS-1D, and the simulation results were verified by field data of nearly four years. Using the validated model, the optimization of design parameters of rainfall return period, filter media depth and type, and surface area was discussed. And the annual hydrologic performance of bioretention systems was further analyzed under the optimized parameters. The study reveals that bioretention systems with underdrains and impervious boundaries do have some detention capability, while their total water retention capability is extremely limited. Better detention capability is noted for smaller rainfall events, deeper filter media, and design storms with a return period smaller than 2 years, and a cost-effective filter media depth is recommended in bioretention design. Better hydrologic effectiveness is achieved with a higher hydraulic conductivity and ratio of the bioretention surface area to the catchment area, and filter media whose conductivity is between the conductivity of loamy sand and sandy loam, and a surface area of 10% of the catchment area is recommended. In the long-term simulation, both infiltration volume and evapotranspiration are critical for the total rainfall treatment in bioretention systems.
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Hidrologia/métodos , Modelos Teóricos , Chuva , Hidrologia/instrumentação , Desenvolvimento Vegetal , Solo , Ciclo HidrológicoRESUMO
INTRODUCTION: The incidence of stroke in working-age adults is increasing. Many patients face cognitive, emotional and physical impairments and their subsequent influences on returning to work. An increasing number of studies have been conducted on the transformation from unemployment to returning to work. The criteria for returning to work only used the 'working yes/no' as the primary outcome. Although some researchers have investigated the characteristics of patients with stroke who have returned to work, there is a paucity of evidence regarding the work situation. This scoping review aimed to examine and map the work situation of patients with stroke who have returned to work. METHODS AND ANALYSIS: This study will be based on the Joanna Briggs Institute Reviewers' Manual for scoping reviews. A systematic literature search will be conducted using related medical subject headings and keywords on the work situation of patients with stroke who have returned to work. Relevant publications will be searched using 17 data sources, including grey literature sources, published in English or Chinese between 1957 and 2022. None of the articles will have restrictions on the data sources or study designs. The study selection and search results will be reported and presented according to the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for scoping reviews flow diagram. The results will be presented in a table format based on the data extraction tool. ETHICS AND DISSEMINATION: This study is exempted from a medical ethical review. This scoping review addresses the knowledge gap by identifying and synthesising the work situation of patients with stroke who have returned to work, which will provide helpful information for various stakeholders. This scoping review will be submitted and published in a peer-reviewed scientific journal.
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Retorno ao Trabalho , Acidente Vascular Cerebral , Adulto , Humanos , Povo Asiático , Pacientes , Projetos de Pesquisa , Desemprego , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Although ALYREF has been demonstrated to have a role in a number of malignancies, its role in hepatocellular carcinoma (HCC) has received little attention. Our objective was to research at the prognostic value, biological role and relevance of ALYREF to the immune system in HCC. METHODS: The expression of ALYREF and its relationship with clinical parameters of HCC patients were analyzed by liver cancer cohort (LIHC) of The Cancer Genome Atlas. The expression and prognosis were verified by immunohistochemistry experiments. Gene transfection, CCK-8, scratch healing, transwell invasion and flow cytometry were used to assess the molecular function of ALYREF in vitro. The TIMER and TISIDB online data portals were used to assess the relevance of ALYREF to immunization. Stepwise regression analysis of ALYREF-related immune genes in the LIHC training set was used to construct a prognostic risk prediction model. Also, construct a nomogram to predict patient survival. The testing set for internal verification. RESULTS: Knockdown of ALYREF changed the biological phenotypes of HCC cells, such as proliferation, apoptosis, and invasion. In addition, the expression of ALYREF in HCC affected the level of immune cell infiltration and correlated with the overall survival time of patients. The constructed immune prognostic model allows for a valid assessment of patients. CONCLUSION: ALYREF is increased in HCC, has an impact on cellular function and the immune system, and might be used as a prognostic marker.
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BACKGROUND: The traditional face-to-face education methods have been altered to E-learning due to the outbreak, and the E-learning adaptability of nursing students will directly affect the effectiveness of online education. The professional identity of nursing students refers to the positive perception, evaluation, and emotional experience of the nursing profession and identity to be undertaken, which may affect the E-learning adaptability of nursing students during the coronavirus disease 2019 (COVID-19). This study aimed to explore the impact of professional identity on the E-learning adaptability of the Chinese nursing students during COVID-19. METHODS: This study was conducted in three medical schools in Yunnan Province, China from August to October 2020. Data collection consisted of three sections: participants' characteristics, learning adaptability, and professional identity. RESULTS: A total of 585 nursing students had a moderate level of E-learning adaptability. There was a positive correlation between E-learning adaptability and professional identity (r = 0.316~0.505, p < 0.001). In addition, the professional identity was associated with predictors of the E-learning adaptability among nursing students (p < 0.001). CONCLUSION: There was a moderate level of E-learning adaptability among the Chinese nursing students during the COVID-19 crisis. Enhancing the professional identity is critical in improving the E-learning adaptability among nursing students.
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COVID-19 , Instrução por Computador , Estudantes de Enfermagem , China , Humanos , SARS-CoV-2RESUMO
OBJECTIVE: To investigate the clinical application of microsurgery using the cerebellar medulla fissure approach in severe ventricular hemorrhage with casting of the fourth ventricle and its effect on neurological recovery. METHODS: A total of 80 patients with severe intraventricular hemorrhage accompanied by casting and dilation of the fourth ventricle who were admitted to the neurosurgery department between July 2019 and December 2020 were randomly divided into an observation group and a control group, with 40 patients in each group. The drainage tube extubation time and length of hospital stay of the two groups were compared. The 3-day hematoma clearance of the two groups was observed. Postoperative consciousness was evaluated by GCS, and the patients' recovery was evaluated by GOS at three months. The activities of daily living (ADL) scores of the two groups were compared to evaluate patients' postoperative self-care ability. The incidence of postoperative complications in the two groups was collected. Independent risk factors for poor prognosis were analyzed by logistics regression. RESULTS: The postoperative hospitalization time and the drainage tube extubation time in the observation group were significantly lower than those in the control group. The ratio of hematoma clearance ≥90% in the observation group was significantly higher than that of the control group. Postoperative GCS scores and GOS scores in the observation group were significantly higher than those of the control group. The rate of postoperative complications in the observation group was significantly lower than that of the control group. The rate of good ADL grading in the observation group was significantly higher than that in the control group. Age and surgical method were independent risk factors for poor prognosis. CONCLUSION: Microsurgery using the cerebellar medulla fissure approach can effectively improve the condition of severe ventricular hemorrhage with casting of the fourth ventricle and promote the recovery of patients' neurological function.
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Most solid tumours are hypoxic. Tumour cell proliferation and metabolism accelerate oxygen consumption. The low oxygen supply due to vascular abnormalisation and the high oxygen demand of tumour cells give rise to an imbalance, resulting in tumour hypoxia. Hypoxia alters cellular behaviour and is associated with extracellular matrix remodelling, enhanced tumour migration, and metastatic behaviour. In light of the foregoing, more research on the progressive and prognostic impacts of hypoxia on gliomas are crucial. In this study, we analysed the expression levels of 75 hypoxia-related genes in gliomas and found that a total of 26 genes were differentially expressed in The Cancer Genome Atlas (TCGA) database samples. We also constructed protein-protein interaction networks using the STRING database and Cytoscape. We obtained a total of 10 Hub genes using the MCC algorithm screening in the cytoHubba plugin. A prognostic risk model with seven gene signatures (PSMB6, PSMD9, UBB, PSMD12, PSMB10, PSMA5, and PSMD14) was constructed based on the 10 Hub genes using LASSO-Cox regression analysis. The model was verified to be highly accurate using subject work characteristic curves. The seven-gene signatures were then analysed by univariate and multivariate Cox. Notably, PSMB10, PSMD12, UBB, PSMA5, and PSMB6 were found to be independent prognostic predictive markers for glioma. In addition, PSMB6, PSMA5, UBB, and PSMD12 were lowly expressed, while PSMB10 was highly expressed, in the TCGA and GTEx integrated glioma samples and normal samples, which were verified through protein expression levels in the Human Protein Atlas database. This study found the prognostic predictive values of the hypoxia-related genes PSMB10, PSMD12, UBB, PSMA5, and PSMB6 for glioma and provided ideas and entry points for the progress of hypoxia-related glioma.
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Carotid-cavernous fistulas (CCFs) are abnormal arteriovenous anastamoses between the carotid artery and the cavernous sinus. These fistulas may be classified by cause (spontaneous or traumatic), flow velocity (high or low), or pathogenesis (direct or indirect). The most commonly adopted classification is that described by Barrow based on arterial supply. Traumatic CCFs are almost always direct shunts between the internal carotid artery (ICA) and the cavernous sinus. General features of CCFs, which may be apparent with any lesion, including bruit, headache, loss of vision, altered mental status and neurological deficits. Some fistulae may present primarily with hemorrhage before any evaluation can be performed. However, hemiparesis has been rarely observed. Only a literature review of Murata et al reported a case of hemiparesis caused by posttraumatic CCF, in which the fistula resulted in venous hypertension and subsequent brainstem congestion. While in our case, cerebral infarction was caused by total steal of the blood flow. The patient recovered after occlusion of the fistula with a detachable balloon.
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Oclusão com Balão/métodos , Fístula Carótido-Cavernosa/diagnóstico por imagem , Fístula Carótido-Cavernosa/terapia , Paresia/diagnóstico , Adulto , Fístula Carótido-Cavernosa/complicações , Angiografia Cerebral , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico , Seguimentos , Humanos , Masculino , Paresia/complicações , Recuperação de Função Fisiológica , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ferimentos não Penetrantes/complicaçõesRESUMO
The aim of this study was to assess the clinical efficacy and safety of mechanically assisted thrombolysis in the treatment of acute cerebral infarction. Mechanically assisted intra-arterial urokinase thrombolysis was conducted on 28 patients with acute cerebral infarction with a disease onset time of 90-450 min. The maximum level of urokinase was 1,150,000 units. Thrombus disruption with a microwire, retrieval with a microcatheter and stent-assisted revascularization were performed. The recanalization rate, bleeding complications and modified Rankin scale (mRS) score were observed within 3 months of surgery. Our results showed that mechanically assisted thrombolysis was successfully conducted on 23 patients, with a recanalization rate of 82.1% (23/28), average recanalization time of 65.22 min and mRS score ≤3.5. Five cases of recanalization were invalid, including 2 cases of mortality, 1 case with an mRS score of 4 and 2 cases with an mRS score ≤3. In the recanalization group, the mechanically assisted thrombolysis did not increase the number of bleeding complications. Our study demonstrated that the safety of mechanically assisted thrombolysis for the treatment of acute cerebral infarction is equivalent to that of simple intra-arterial thrombolysis, but that the former has a higher efficiency. Mechanically assisted thrombolysis is able to reduce the urokinase dosage and recanalization time, and increase the recanalization rate.
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This paper discussed the advance in ecological and environmental water requirement (EEWR) study, including its conception, classification, calculation methods, and others. At abroad, the EEWR study is concentrated on rivers, and a more applicable methodology has been established; while in China, it is focused on land and river in the interior river basins of the northwestern areas, the Yellow River Basin, the Haihe river basin and the Luanhe river basin, where the water shortage problem is serious. Many achievements of great significance in the EEWR study at home and abroad have been achieved, but there are still many other ambiguous and unknown issues to be further studied in the future, summarized as: (1) the studies on the EEWR theory (including its conception, classification, calculation methods, etc.) should be strengthened; (2) it is necessary to reinforce some aspects of the EEWR study, such as the internal and external affecting factors of EEWR, the engineering approaches or measures to meet EEWR, etc.; (3) it is urgent to expand the applied research of EEWR and to realize the optimized allocation of water resources.
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Ecossistema , Meio Ambiente , Rios , Abastecimento de Água , Conservação dos Recursos Naturais , Movimentos da ÁguaRESUMO
It is well known that the development of water-saving agriculture is a strategic choice for getting rid of the crisis of water shortage. In this paper, the crop photosynthesis, transpiration, stomatic behavior, and their affecting factors were studied in view of increasing the crop water use efficiency. The experimental results showed that there was a parabola relationship between photosynthesis and transpiration. The transpiration at the maximum photosynthesis was a critical value, above which, transpiration was the luxurious part. The luxurious transpiration could be controlled without affecting photosynthetic production. It is possible that the measures for increasing stomatic resistance and preventing transpiration could save water, and improve photosynthesis and yield as well. The photosynthesis rate increased with photosynthetic active radiation, and the light saturation point for photosynthesis existed. The light saturation point of dry treatment was much lower than that of wet treatment, and the relationship between transpiration and radiation was linear. When the photosynthetic active radiation was bigger than 1,000 mumol.m-2.s-1, some treatments could be carried out for decreasing transpiration and improving photosynthesis.