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The transporter protein ABC subfamily G member 2 (ABCG2) is implicated in epilepsy; however, its specific role remains unclear. In this study, we assessed changes in ABCG2 expression and its role in epilepsy both in vitro and in vivo. We observed an instantaneous increase in ABCG2 expression in epileptic animals and cells. Further, ABCG2 overexpression significantly suppressed the oxidative stress and apoptosis induced by glutamate, kainic acid (KA), and lipopolysaccharide (LPS) in neuronal and microglia cells. Furthermore, inhibiting ABCG2 activity offset this protective effect. ABCG2-deficient mice (ABCG2-/-) showed shorter survival times and decreased survival rates when administered with pentylenetetrazole (PTZ). We also noticed the accumulation of signal transducer and activator of transcription 1 (STAT1) and decreased phosphorylation of mammalian target of rapamycin kinase (mTOR) along with increased ISGylation in ABCG2-/- mice. ABCG2 overexpression directly interacted with STAT1 and mTOR, leading to a decrease in their ISGylation. Our findings indicate the rapid increase in ABCG2 expression acts as a shield in epileptogenesis, indicating ABCG2 may serve as a potential therapeutic target for epilepsy treatment.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Apoptose , Epilepsia , Estresse Oxidativo , Fator de Transcrição STAT1 , Serina-Treonina Quinases TOR , Animais , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética , Camundongos , Epilepsia/metabolismo , Epilepsia/genética , Serina-Treonina Quinases TOR/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Camundongos Knockout , Humanos , Ácido Caínico , Neurônios/metabolismo , Neurônios/patologia , Microglia/metabolismo , Masculino , Modelos Animais de Doenças , Transdução de SinaisRESUMO
Microplastics (MPs) pollution is a pressing environmental issue for aquatic ecosystems. Landfill leachate is an important contributor of MPs and antibiotic resistant genes (ARGs). However, there are few studies on the colonization of ARGs and pathogens on MPs in leachate. This study conducted incubation experiments with polyethylene terephthalate (PET) and polypropylene (PP) MPs in landfill leachate which were about 3-5 years old (PL) and 5-10 years old (AL). After incubation, the bacterial cells colonized and grew on the surface of MPs, inducing the increase of oxygenated oxygen functional groups (e.g., hydroxyl, carbonyl) on the MPs surface. Real-time PCR indicated that MPs selectively enriched ARGs, such as genes tetM, tetC, mcr-1, aac(6')-Ib-cr, blaTEM and blaSHV in leachate. The diversity of bacterial communities on MPs was significantly increased in AL leachate, but decreased in PL leachate. The differences in bacterial communities in MPs biofilms were related to the type of MPs. Compared with AL leachate, the abundance of Chloroflexi increased by 15.7% on the PET, and the abundance of Acidobacteriota increased by 6.23 fold on the PP. The abundance of Firmicutes increased from 20.7% in PL leachate to 65.8% and 60.7% on PET and PP, respectively. Additionally, pathogens were observed to be more abundant on MPs compared to leachate. In particular, pathogens (Staphylococcus, Streptococcus, Enterobacter and Rhodococcus) associated with sul1 and sul2 were generally present at higher levels on MPs than in the surrounding leachate. These results provide significant implications for understanding the health risk of MPs in the environment.
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Poluentes Químicos da Água , Poluentes Químicos da Água/toxicidade , Ecossistema , Microplásticos , Plásticos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Polietilenotereftalatos , PolipropilenosRESUMO
Wastewater treatment plants can be nanoplastics (NPs) and microplastics (MPs) sinks and sources. The effects of NPs and MPs on nitrogen removal and extracellular polymeric substances (EPS) during activated sludge process need further investigation. Results showed that polystyrene NPs (NPS) and 100 mg/L polystyrene MPs (MPS) decreased the specific nitrate reduction rate, resulting in nitrate accumulation. The negative effects on functional genes involved in denitrification (narG, napA, nirS and nosZ) were the main mechanism. NPS stimulated EPS secretion, but MPS inhibited it. NPS and MPS increased the ratio of protein to polysaccharide except for 10 mg/L MPS and changed the secondary structure of protein in EPS, affecting flocculation ability of activated sludge. The changes of microbial abundance in activated sludge could be the main factor to the alterations of EPS and nitrogen removal. These results may facilitate understanding the impacts of NPs and MPs on wastewater treatment processes.
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Microbiota , Esgotos , Esgotos/química , Microplásticos/análise , Microplásticos/farmacologia , Matriz Extracelular de Substâncias Poliméricas/química , Plásticos , Poliestirenos , Desnitrificação , Nitrogênio/análise , Nitratos/farmacologia , Reatores Biológicos , Eliminação de Resíduos LíquidosRESUMO
Epilepsy is one of the most common serious chronic neurological diseases affecting people of all ages globally. It is characterized by recurrent seizures. About 50 million people worldwide have epilepsy. Indubitably, people with epilepsy (PWE) may be without access to appropriate treatment. Many studies have examined the molecular mechanisms and clinical aspects of epilepsy; nonetheless, the treatment gap exists in some special areas. In the tropics, the specific geographical and ecological conditions and a lack of medical resources result in neglect or delay of diagnosis for PWE. Herein, we summarized the epidemiology of epilepsy in the tropics and discussed the disease burden and existing problems, aiming to offer a medical environment for patients in need and highlight the importance of reducing the epileptic disease burden in tropical countries.
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Epilepsia Generalizada , Epilepsia , Humanos , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Efeitos Psicossociais da Doença , Dano Encefálico CrônicoRESUMO
Microplastics (MPs) could serve as vectors of antibiotics and heavy metals through sorption and desorption. However, the combined adsorption process of antibiotics and heavy metals on aged MPs has rarely been studied. In this study, combined adsorption/desorption of tetracycline (TC) and Cd(II) on/from polystyrene (PS) and polyethylene terephthalate (PET) MPs, as well as ultraviolet (UV) and H2O2 aged MPs, was investigated. The specific surface areas of the MPs increased after UV and H2O2 aging. Adsorption experiments showed that the pseudo-second-order kinetic model and Freundlich model fitted adsorption of TC and Cd(II) on all of the MPs. The adsorption capacities of TC and Cd(II) were higher on aged MPs than on the pristine MPs, especially on H2O2 treated MPs. TC adsorption on the MPs was hardly affected by Cd(II), and Cd(II) adsorption was not significantly affected by TC when the solution pH value was below 8.0. Cd(II) slightly enhanced TC adsorption on the MPs at pH 8.0, especially on the aged MPs. The TC adsorption capacities increased with increasing pH, reaching a maximum at pH 5.0 or 6.0, and they then decreased, while the largest level of Cd(II) adsorption was at approximately pH 6.0. Adsorption of TC and Cd(II) on the pristine and aged MPs was thermodynamically favorable and spontaneous. The trend of the desorption rates of TC and Cd(II) from the MPs in different background solutions was ultrapure water < surface water < simulated gastric fluid. The desorption rates of TC and Cd(II) from the aged MPs were lower than those from the pristine MPs. The results revealed the mechanism of the TC and Cd(II) combined adsorption process on aged MPs, which will provide insight for understanding the aging process and its potential effects on sorption and desorption of antibiotics and heavy metals in the real environment.
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Compostos Heterocíclicos , Metais Pesados , Poluentes Químicos da Água , Antibacterianos/análise , Cádmio , Peróxido de Hidrogênio , Microplásticos , Plásticos , Polietilenotereftalatos , Poliestirenos , Tetraciclina/análise , Água , Poluentes Químicos da Água/análiseRESUMO
Ischemic stroke caused by atherosclerosis (AS) poses a serious threat to human life expectancy and quality. With the development of genome-wide association studies, the association of histone deacetylase 9 (HDAC9) expression of atheromatous plaques with ischemic stroke in large arteries has been revealed, but the molecular mechanisms behind this phenomenon have not been elucidated. In this study, we explored the effect of HDAC9 on the P38 mitogen activated protein kinase (P38 MAPK), a classic cellular inflammation-related pathway, by knocking down HDAC9 in vascular endothelial cells with short hairpin RNA (shRNA) and found that HDAC9 may mediate oxidized low density lipoprotein (ox-LDL)-induced inflammatory injury in vascular endothelial cells by regulating the phosphorylation level of P38 MAPK to lead to AS. It can be seen that HDAC9 may be a target to control the formation of atherosclerotic plaques. In follow-up experiments, it was verified that sodium valproate (SVA), as a HDAC9 inhibitor, can indeed antagonize the inflammatory damage of vascular endothelial cells, as well as SB203580, which is a P38 MAPK inhibitor. It proves that SVA may be a potential drug for the prevention and treatment of ischemic stroke.
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Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Histona Desacetilases/genética , Sistema de Sinalização das MAP Quinases , Proteínas Repressoras/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Biomarcadores , Células Cultivadas , Suscetibilidade a Doenças/patologia , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/patologia , Técnicas de Silenciamento de Genes , Histona Desacetilases/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Inibidores de Proteínas Quinases , RNA Interferente Pequeno , Proteínas Repressoras/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
OBJECTIVE: To explore the effects of a nurse-led hierarchical management model for managing the out-of-hospital asthma control and quality of life in children with bronchial asthma. METHODS: A prospective randomized controlled study was designed. Children with bronchial asthma treated in our hospital were recruited as the study cohort and randomly divided into a test group (n=60) and a control group (n=60). After their discharge from the hospital, the children with bronchial asthma in both groups underwent out-of-hospital management led by nurses. In addition to this management, the test group underwent hierarchical management according to the results of their social living ability and temperament type evaluations. The levels of control of the asthma within 6 months after discharge were compared between the two groups. The changes in the asthma control test (ACT) scores, the daily variation rates in the peak expiratory flows (PEF), the pulmonary functions, the changes in the airway inflammation indicators, and the two groups' quality of life were compared. In addition, univariate and multivariate logistic regressions were used to analyze the factors influencing the acute asthma attacks in children. RESULTS: Compared with the control group, the number of acute asthma attacks, the emergency medical treatment and hospitalization rates in children with acute asthma attacks within 6 months were significantly decreased in the test group (P<;0.05). After 3 and 6 months of the nursing, the test group had better ACT scores, better daily PEF variation rates, better pulmonary function, better serum inflammatory factors, better Medication Adherence Report Scale for Asthma (MARS-A) scores, and better pediatric asthma quality of life questionnaire (PAQLQ) scores than the control group (all P<;0.05). A multivariate logistic regression analysis showed that acute asthma attacks in childhood asthma were associated with the age of the first attack ≤f years (OR=3.635), a family history of rhinitis/asthma (OR=1.425), poor medication adherence (OR=1.855), the baseline IgE level (OR=1.305), and the hierarchical nursing management (OR=0.593). CONCLUSIONS: A nurse-led hierarchical management model can effectively improve the level of out-of-hospital asthma control in children with bronchial asthma and can improve their pulmonary function and quality of life as well.
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PURPOSE: To compare endovascular and drug therapies for efficacy and safety in patients with a progressive stroke caused by intracranial large vascular occlusion exceeding the time window of 24 hours. PATIENTS AND METHODS: A total of 58 patients with progressive stroke caused by large intracranial vascular occlusion exceeding the time window of 24 hours treated in the stroke center of our hospital for three years were retrospectively analyzed . According to the applied therapy, 58 patients were divided into the endovascular (n = 19) and drug (n = 39) therapy groups. Then, modified Rankin scale (mRS) scores, symptomatic intracranial hemorrhage rates, mortality rates and adverse events were assessed in both groups within 90 days. RESULTS: The 90-day good prognosis rate was significantly higher in the endovascular therapy group compared with the drug group (68.4% VS 38.5%, odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.09-0.92; P = 0.032). The 90-day NIHSS scores were lower in the endovascular therapy group compared with the drug group (3.3 ± 2.6 VS 5.2 ± 3.0, OR = -1.89; 95%CI, -3.50 to -0.27; P = 0.023). Meanwhile, the proportion of patients with a Barthel index of 90-100 was significantly higher in the endovascular therapy group compared with the drug group (53.0% VS 25.6%, OR = 0.31; 95%CI, 0.10-0.98; P = 0.042). Finally, both groups showed similar rates of adverse events. CONCLUSION: In patients with progressive stroke caused by large intracranial vascular occlusion exceeding 24 hours, endovascular therapy probably results in improved efficacy at 90 days compared with drug therapy, without increasing the rates of adverse effects.
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Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/cirurgia , Resultado do Tratamento , Anticoagulantes/uso terapêutico , Procedimentos Endovasculares/métodos , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , Tempo para o TratamentoRESUMO
OBJECTIVE: Epilepsy is a chronic neurological disease that is characterized by seizures. Seizure episodes, stigma, and high medical costs associated with this condition caused significant psychological distress. This study aimed to evaluate epidemiological characteristics and treatment status of epilepsy in individuals existing in the tropical rural areas of Hainan Province of China. METHODS: A household survey on epilepsy was conducted among the rural population of Chengmai County, Danzhou City, Baoting Autonomous County (Li and Miao nationalities), and Dingan County in Hainan Province, China. A screening questionnaire based on the standard screening questionnaires of the World Health Organization (WHO) was designed and a screening instrument of International Community-based Epilepsy Research Group was used. Individuals suspected or previously diagnosed with epilepsy were reexamined by an experienced neurologist. Further clinical data were collected from subjects with confirmed diagnosis of epilepsy. RESULTS: This study included 16 676 subjects with 8827 men (52.93%) and 7849 women (47.07%). Majority of the study subjects included were of Han Chinese (N = 13 145, 78.83%), and the remaining were of Li minority ethnicity. The incidence of epilepsy was 0.24 per 1000, and the total prevalence of active epilepsy was 2.33 per 1000. The prevalence of epilepsy in the Han and Li nationalities was 3.27 and 2.27 per 1000, respectively, which was shown to be higher in people aged ≥ 60. The initial onset of epilepsy tended to trigger among children aged between 0 and 9 years old. Initial assessment revealed that the treatment gap for active epilepsy was 58.97%, and stroke is shown as the most common cause of symptomatic epilepsy. SIGNIFICANCE: The prevalence and incidence of epilepsy in tropical rural areas of Hainan Province were close to those of the earlier findings that are reported in other regions of China and lower than those remaining in the tropical areas around the world. There exists a huge treatment gap for active epilepsy, which indicates an urgent need for a rational intervention strategy.
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Epilepsia , Idoso , Criança , Pré-Escolar , China/epidemiologia , Epilepsia/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , População Rural , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVE: Sphingosine-1-phosphate (S1P) receptors are extensively used in the treatment of multiple sclerosis (MS). However, the optimal therapeutic role of S1P in MS patients has still remained elusive. This network meta-analysis (NMA) systematically evaluated the efficacy and acceptability of S1P receptors, as disease-modifying drugs, in the treatment of patients with MS, so as to find out the most appropriate therapeutic strategy and provide a reliable basis for the prescription of S1P drugs for patients with MS. METHODS: We conducted a systematic review and NMA to compare the efficacy and acceptability of S1P receptors for treating MS patients. Randomized controlled trials (RCTs), which were published until May 2020, were retrieved from the PubMed, Cochrane Library, Embase, and ClinicalTrials.gov databases. The primary outcome in this study was the treatment efficacy for the S1P receptor for MS patients, in terms of decrease in annualized relapse rate. The secondary outcomes were adverse events leading to discontinuation of a study, such as an unfavorable or unintended sign/symptom. Outcomes were appraised using a random effects model expressed as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities for hierarchical clustering of interventions. RESULTS: A total of 13 RCTS were included, which enrolled 10,554 patients. The results of NMA showed that Fingolimod, Laquinimod, Siponimod, Ozanimod, Amiselimod, and Ponesimod were superior to placebo in terms of reducing the annualized relapse rate of MS patients. Regarding efficacy, the best and worst treatments were Amiselimod (0.4 mg; SUCRA 8.1%) and placebo (SUCRA 90.5%), respectively. As for acceptability, the best and worst interventions were Ozanimod (1 mg; SUCRA 20.4%) and Ponesimod (40 mg; SUCRA 96.0%), respectively. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed that there was no significant funnel plot asymmetry CONCLUSIONS: This NMA indicated that Amiselimod (0.4 mg) is the most effective treatment strategy as a S1P receptor for MS patients. However, the abovementioned findings need to be further confirmed in the next researches.
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Esclerose Múltipla , Recidiva Local de Neoplasia , Humanos , Esclerose Múltipla/tratamento farmacológico , Metanálise em Rede , Receptores de Esfingosina-1-Fosfato , Resultado do TratamentoRESUMO
BACKGROUND: Breast cancer (BC) is common cancer in female globally. Sevoflurane (SEV) has been reported to inhibit the metastasis of multiple cancers, including glioma, colorectal cancer, and hepatocellular carcinoma. However, the role of SEV in the metastasis of BC cells remains poorly understood. METHODS: Transwell migration and invasion assays were performed to detect the migration and invasion of BC cells. Western blot assay was carried out to measure epithelial-mesenchymal transition (EMT)-related proteins in BC cells, including E-cadherin, N-cadherin, and fibronectin. Quantitative real-time polymerase chain reaction was conducted to determine the enrichment of miR-139-5p and ADP-ribosylation factor 6 (ARF6) in BC tissues and cells. The protein expression of ARF6 in BC tissues and cells was measured by western blot assay. The target of miR-139-5p was predicted by starBase software, and the target relationship between miR-139-5p and ARF6 in BC cells was confirmed by dual-luciferase reporter assay. RESULTS: SEV suppressed the migration, invasion, and EMT of BC cells, especially in the high-concentration SEV group. The level of miR-139-5p was lower in BC tissues and cells than that in paired normal tissues and normal mammary epithelial cells MCF-10A. MiR-139-5p was upregulated in BC cells treated with SEV. ARF6 was upregulated in BC tissues and cells compared with that in corresponding normal tissues and normal mammary epithelial cells MCF-10A. SEV reduced the mRNA and protein expression of ARF6 in BC cells. The accumulation of ARF6 or the interference of miR-139-5p reversed the suppressive effects of SEV treatment on the migration, invasion, and EMT of BC cells. MiR-139-5p bound to ARF6 and inversely modulated the level of ARF6 in BC cells. The transfection of si-ARF6 attenuated the promoting effects of miR-139-5p depletion on the migration, invasion, and EMT of BC cells treated with SEV. CONCLUSIONS: SEV suppressed the migration, invasion, and EMT of BC cells through downregulating the abundance of ARF6 by upregulating miR-139-5p. The miR-139-5p/ARF6 axis might be a promising target for the treatment of BC.
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Anestésicos Inalatórios/farmacologia , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Sevoflurano/farmacologia , Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP/metabolismo , Avaliação Pré-Clínica de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , MicroRNAs/metabolismoRESUMO
Glioblastoma (GBM) is the most common malignant primary tumor in the human central nervous system. The present study aimed to explore the molecular mechanism by which microRNA (miR)-181a-5p targets the F-box protein 11 (FBXO11) in glioma cells to inhibit cell proliferation and invasion. Reverse transcription-quantitative (RT-q)PCR was performed to detect the expression levels of miR-181a-5p in U251TR cells, U251 cells, primary GBM tissues and relapsed GBM tissues in order to determine the association between miR-181a-5p and the chemoresistance of GBM cells. The expression levels of miR-181a-5p in GBM cells were modulated via transfecting miR-181a-5p mimics and inhibitors. Cell Counting Kit-8 assays were undertaken to assess the effects of miR-181a-5p on drug sensitivity and proliferation of GBM cells. Wound healing assays were performed to examine the effects of miR-181a-5p on the migratory ability of GBM cells. Furthermore, the effects of miR-181a-5p on the invasive ability of GBM cells were analyzed using an in vitro invasion assay. Flow cytometry analysis was carried out to determine whether overexpression of miR-181a-5p can promote the apoptotic rate of GBM cells. RT-qPCR and western blotting were employed to detect the effects of miR-181a-5p on mRNA and protein expression of FBX011. miR-181a-5p exhibited low expression in resistant GBM cell lines and recurrent tumor tissues. Dual-luciferase reporter assays were utilized to detect luciferase activity to verify the targeted regulatory association between miR-181a-5p and FBXO11. Upregulation of miR-181a-5p promoted the sensitivity of GBM cells to temozolomide (TMZ), increased the apoptotic rate of GBM cells and significantly inhibited the invasive and migratory capacities of GBM cells. In drug-resistant glioma cells, compared with the miR-negative control group and the blank group, the expression of miR-181a-5p was significantly upregulated (P<0.01), while the expression of FBXO11 protein was downregulated. miR-181a-5p increased the sensitivity of GBM cells to TMZ. miR-181a-5p significantly inhibited the migratory and invasive capacities of GBM cells. miR-181a-5p may become a novel effective target for the treatment of GBM. The results of dual-luciferase reporter assays indicated that miR-181a-5p could target the 3'-untranslated region of FBXO11. The underlying mechanism may be targeted inhibition of FBXO11 gene expression, or may be associated with apoptosis.
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SPARC (secreted protein acidic and rich in cysteine) family of proteins is a class of protein involved in tissue development and repair by regulating cell adhesion, proliferation, metastasis, and growth factor signaling to affect the extracellular matrix (ECM) and interactions between cells. Although being highly valued in non-nerve tissues, studies in both cell and animal models have been revealed that SPARC family proteins may also continue to play a vital role in central nervous system (CNS) diseases and development. These SPARC family proteins are widely expressed in the CNS of normal people, and significantly increased in brain tissue following disease or injury, such as SPARC, SPARCL-1, FSTL-1 and testican. In our review, we will pay attention to the functions of SPARC family proteins in autophagy, apoptosis, angiogenesis, adipogenesis, inflammatory response, and cerebral tissue development, injury and repair mainly including but not limited to axon regeneration, formation of glial scar, neural plasticity, regulation of nerve conduction related receptors and rewiring of neural circuitry.
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Doenças do Sistema Nervoso Central/metabolismo , Regeneração Nervosa/fisiologia , Osteonectina/metabolismo , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/patologia , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologiaRESUMO
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein involved in the extracellular matrix and interactions between cells during neural development of the central nervous system (CNS). Oxidative glutamate toxicity is involved in CNS diseases, including epilepsy, Alzheimer's disease, and ischemic stroke. However, the molecular mechanism of nerve injury is not fully understood in CNS diseases. Herein, the glutamate-induced nerve damage model was used to explore the molecular mechanisms affecting nerve damage. The levels of SPARC and autophagy were increased in glutamate-induced HT22 hippocampal nerve injury. In summary, the current study confirmed that SPARC regulates autophagy in HT22 hippocampal nerve cells, and its knockdown reduces the glutamate-induced HT22 hippocampal nerve injury by inhibiting autophagy. These findings suggested that SPARC plays a crucial role in nerve injury of CNS diseases.
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Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.
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The digital economy has substantially reduced market frictions but also posed new challenges for the efficient functioning of markets. In particular, the drastic reductions in the costs of search, entry, transportation, and reproduction have profound implications for the role of platforms, the value of innovation, and the balance between firms' data needs and consumer privacy. I review some recent economic research that sheds light on these issues, and discuss how well-designed policies on competition, regulation, IP protection, and consumer privacy can improve market performance in the digital economy.
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BACKGROUND: To evaluate the impacts of nurse-led clinic and nurse-led prescription on hemoglobin A1c (HbA1c) control in type 2 diabetes. METHODS: We searched relevant publications in English and Chinese database and conducted meta-analysis by Stata 12.0. We divided the case groups of included studies into 2 categories according to the role of nurse: nurse-led clinic and nurse-led prescription. Nurse-led clinic was implemented on the basis of standard diabetes care provided by doctor, and control group also receive the standard diabetes care but without nurse-led clinic. The doctor mentioned above might work alone or in a health care team. Nurse-led prescription was prescribed by nurse independently and compared with that of doctor. RESULTS: The meta-analysis shown that, compared with the standard diabetes care, nurse-led clinic significantly decreases HbA1c level (standard mean difference [SMD]â=â-0.767; 95% confidence interval [CI]: -1.062, -0.471; Pâ<â.001). In subgroup analysis, nurse-led clinic also had positive impacts on controlling HbA1c level, no matter in developed countries (SMDâ=â-0.353; 95% CI: -0.6, -0.106; Pâ=â.005) or developing countries (SMDâ=â-1.114; 95% CI: -1.498, -0.73; Pâ<â.001). Additionally, there was no significant difference between nurse-led prescription and doctor prescription in controlling HbA1c levels (SMDâ=â-0.203; 95% CI: -0.434, 0.029; Pâ=â.086). CONCLUSION: The nurse-led clinic had positive significance for HbA1c control. Meanwhile, the impact of nurse-led prescription on controlling HbA1c is comparable to that of doctor. It is valuable to provide nurse-led clinic on the basis of standard diabetes care provided by doctor to better control HbA1c, and nurse-led prescription should be provided when doctor-led service is limited.
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Diabetes Mellitus Tipo 2/enfermagem , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Padrões de Prática em Enfermagem/estatística & dados numéricos , Prescrições/enfermagem , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cervical cancer is one of the most aggressive human cancers with poor prognosis due to constant chemoresistance and repeated relapse. Tubeimoside I (TBM) has been identified as a potent antitumor agent that inhibits cancer cell proliferation by triggering apoptosis and inducing cell cycle arrest. Nevertheless, the detailed mechanism remains unclear and needs to be further elucidated, especially in cervical cancer. In this study, we found that TBM could induce proliferation inhibition and cell death in cervical cancer cells both in vitro and in vivo. Further results demonstrated that treatment with TBM could induce autophagosome accumulation, which was important to TBM against cervical cancer cells. Mechanism studies showed that TBM increased autophagosome by two pathways: First, TBM could initiate autophagy by activating AMPK that would lead to stabilization of the Beclin1-Vps34 complex via dissociating Bcl-2 from Beclin1; Second, TBM could impair lysosomal cathepsin activity and block autophagic flux, leading to accumulation of impaired autophagolysosomes. In line with this, inhibition of autophagy initiation attenuated TBM-induced cell death, whereas autophagic flux inhibition could exacerbated the cytotoxic activity of TBM in cervical cancer cells. Strikingly, as a novel lethal impaired autophagolysosome inducer, TBM might enhance the therapeutic effects of chemotherapeutic drugs towards cervical cancer, such as cisplatin and paclitaxel. Together, our study provides new insights into the molecular mechanisms of TBM in the antitumor therapy, and establishes potential applications of TBM for cervical cancer treatment in clinic.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Lisossomos/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Classe III de Fosfatidilinositol 3-Quinases/genética , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Células HeLa , Humanos , Lisossomos/metabolismo , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Atrial myxoma is the most common type of primary cardiac tumor and it is closely associated with stroke in adults. Early diagnosis and treatment of atrial myxomas is essential for the prevention of embolic events. The aim of the present study was to assess neurological complications associated with atrial myxoma. The neurological signs of atrial myxoma were retrospectively assessed in individuals who underwent treatment at West China Hospital (Chengdu, China) and The Affiliated Hospital of Hainan Medical University (Haikou, China), between March 2003 and February 2015. A total of 130 patients with atrial myxoma were included and 22 (17%) exhibited neurologic signs. These patients were aged 39.9±12.6 years (range, 13-78 years) and there were 13 female and 9 male patients. Ischemic cerebral infarct constituted the dominant clinical symptom (68.2%) and 3 patients exhibited concomitant cardiac manifestations. Atrial myxoma was diagnosed by echocardiography in all patients. Irregular surface of atrial myxomas was associated with a high risk of embolic events. The patients with myxoma successfully underwent surgery with no mortality recorded. In conclusion, atrial myxomas frequently manifest as cerebral infarction in individuals without cardiovascular risk factors. These tumors more commonly affect the middle cerebral artery. Irregular surface of myxomas appears to be associated with embolic events. Echocardiography may improve the diagnosis and early treatment of atrial myxomas.