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Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.
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Epilepsia do Lobo Temporal , Serpinas , Animais , Camundongos , Astrócitos/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Ácido Caínico/toxicidade , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Convulsões/induzido quimicamente , Convulsões/metabolismo , Transdução de Sinais , Serpinas/metabolismoRESUMO
OBJECTIVES: We aimed to observe the relationship between serum 25-hydroxyvitamin D (25-[OH] D) and different cognitive domains, and to evaluate the predictive value of 25-(OH) D level for cognitive impairment in patients with white matter lesions (WML). METHODS: The differences in clinical data including 25-(OH) D were analyzed between cognitive normality (n = 87) and impairment (n = 139) groups, and variant cognitive domains were analyzed between groups of different levels of serum 25-(OH) D. Risk factors for cognitive impairments were evaluated with multivariate logistic regression analysis; a receiver operating characteristic (ROC) curve of 25-(OH) D levels was used to examine the association between 25-(OH) D and WML with cognitive dysfunction. RESULTS: As the severity of WML increased, the proportion of patients with a low level of serum 25-(OH) D increased (p < 0.05). The total MoCA (Montreal Cognitive Assessment) scores and all domain scores except naming were significantly lower in patients with low levels of serum 25-(OH) D than in patients with high levels of serum 25-(OH) D (p < 0.05). Multivariate logistic regression analyses showed that serum 25-(OH) D levels were independently correlated with cognitive impairment. In the ROC analysis, the optimal cut-off value for 25-(OH) D was 17.53 with 76% sensitivity and 70% specificity (AUC =0.751, 95% CI: 0.674-0.819, p < 0.05). CONCLUSION: We observed that vitamin D deficiency is associated with multiple areas of cognitive impairment and that it is an independent risk factor for cognitive impairment in WML.
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Disfunção Cognitiva/epidemiologia , Leucoencefalopatias/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Estudos Transversais , Feminino , Humanos , Leucoencefalopatias/sangue , Leucoencefalopatias/complicações , Modelos Logísticos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Vitamina D/sangue , Substância Branca/patologiaRESUMO
BACKGROUND: Astrocyte and microglia activation are well-known features of temporal lobe epilepsy that may contribute to epileptogenesis. However, the mechanisms underlying glia activation are not well understood. Long non-coding RNA (lncRNA) H19 has diverse functions depending on physiological or pathological state, and its role in epilepsy is unknown. We previously demonstrated that H19 was significantly upregulated in the latent period of epilepsy and may be associated with cell proliferation and immune and inflammatory responses. We therefore speculated that H19 is involved in the hippocampal glial cell activation during epileptogenesis. METHODS: H19 was overexpressed or knocked down using an adeno-associated viral vector delivery system. A rat status epilepticus model was induced by intra-amygdala kainic acid injection. Astrocyte and microglia activation were assessed by immunofluorescence and western blot analyses. Expression of proinflammatory cytokines and components of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were evaluated with western blotting. RESULTS: H19 overexpression induced the activation of astrocytes and microglia and the release of proinflammatory cytokines (interleukin-1ß and interleukin-6 and tumor necrosis factor-α) in the hippocampus, whereas H19 knockdown inhibited status epilepticus-induced glial cell activation. Moreover, H19 activated JAK/STAT signaling by promoting the expression of Stat3 and c-Myc, which is thought to be involved in astrocyte activation. CONCLUSIONS: LncRNA H19 contributes to hippocampal glial cell activation via modulation of the JAK/STAT pathway and could be a therapeutic tool to prevent the development of epilepsy.
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Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neuroglia/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/fisiologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/induzido quimicamente , Regulação da Expressão Gênica/genética , Janus Quinases/metabolismo , Ácido Caínico/toxicidade , Masculino , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Transdução GenéticaRESUMO
Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown. In the present study, high-throughput microarray analysis was used to explore the influence of H19 on gene expression in an epileptic rat model. A large number of genes were differentially expressed at the transcriptional level when H19 was overexpressed or knocked down. Series test of cluster analysis further distinguished genes associated with H19. Function and pathway analyses demonstrated that H19 has diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis, and activation of MAPK. This study implicates H19 in a broad spectrum of epileptogenic processes, thereby providing a range of targets for further mechanistic investigations.
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Epilepsia/genética , Sequenciamento de Nucleotídeos em Larga Escala , RNA Longo não Codificante/genética , Animais , Análise por Conglomerados , Modelos Animais de Doenças , Masculino , RNA Longo não Codificante/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Through collecting and collating the development process of traditional Chinese medicine dispensing, the development of modern Chinese medicine dispensing on the basis of experience could be promoted. "Heyaofenji", "Hehe", " Heji" in ancient Chinese medicine, herbal medicine literature and law were collected, and then things were sorted out according to traditional Chinese medicine dispensing theory, skills and legal norms. Firstly, "Tang Ye Jing Fa" is the earliest book which marks the rudiment of traditional Chinese medicine dispensing. Secondly, traditional Chinese medicine dispensing theory formed in "Shen Nong's herbal classic". Thirdly, Zhang Zhongjing's "Treatise on Febrile Diseases" marked the formation of Chinese medicine dispensing skills. Lastly, Provisions in Tang Dynasty law marks the development of traditional Chinese medicine dispensing.
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Química Farmacêutica/história , Composição de Medicamentos/história , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa/história , Química Farmacêutica/educação , Química Farmacêutica/legislação & jurisprudência , Química Farmacêutica/métodos , China , Formas de Dosagem , Composição de Medicamentos/métodos , Controle de Medicamentos e Entorpecentes/história , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , História Antiga , Medicina na Literatura , Medicina Tradicional Chinesa/métodosRESUMO
OBJECTIVE: To analyze the associated factors with stimulation-induced seizures (SIS) and the relevant factors in predicting surgical outcomes. METHODS: We analyzed 80 consecutive epilepsy patients explored by stereo-electroencephalography with routine electrical stimulation mapping (ESM). If seizures induced by ESM, patients were classified as SIS-positive (SIS-P); otherwise, SIS-negative (SIS-N). Patients received radical surgery were further classified as favorable (Engel I) and unfavorable (Engel II-IV) groups. RESULTS: Of the 80 patients included, we identified 44 (55.0%) and 36(45.0%) patients in the SIS-P and SIS-N groups, respectively. Multivariate analysis revealed that the seizure onset pattern (SOP) of preceding repetitive epileptiform discharges following LVFA (PREDâLVFA) (OR 3.319, 95% CI 1.200-9.183, P = 0.021) and pathology of focal cortical dysplasia (FCD) type II (OR 3.943, 95% CI 1.093-14.226, P = 0.036) were independent factors influencing whether the electrical stimulation can induce a seizure. Among the patients received radical surgery, there were 55 and 15 patients in the favorable and unfavorable groups separately. Multivariate analysis revealed that the SOP of PREDâLVFA induced seizures by stimulation (OR 11.409, 95% CI 1.182-110.161, P = 0.035) and bilateral implantation (OR 0.048, 95% CI 0.005-0.497, P = 0.011) were independent factors affecting surgical outcomes. The previous epilepsy surgery had a trend to be a negative factor with SIS (OR 0.156, 95% CI 0.028-0.880, P = 0.035) and surgical outcomes (OR 0.253, 95% CI 0.053-1.219, P = 0.087). CONCLUSION: ESM is a highly valuable method for localizing the seizure onset zone. The SOP of PREDâLVFA and FCD type II were associated with elicitation of SIS by ESM, whereas a previous epilepsy surgery showed a negative association. Furthermore, the SOP of PREDâLVFA together with SIS in the same patient predicted favorable surgical outcomes, whereas bilateral electrode implantation predicted unfavorable outcomes.
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Líquidos Corporais , Convulsões , Humanos , Convulsões/cirurgia , Estimulação Elétrica , Resultado do TratamentoRESUMO
Objective: We aimed to evaluate the effect of vitamin D supplementation in post-stroke fatigue (PSF) patients with vitamin D deficiency on fatigue symptoms and outcomes. Methods: Patients with primary acute ischemic stroke (AIS) were recruited consecutively from July 2016 to June 2018. Post-stroke fatigue patients were screened out with the Fatigue Severity Scale (FSS) questionnaire, serum concentrations of 25-hydroxyvitamin D [25-(OH)-D] were assessed with enzyme-linked immunosorbent assay (ELISA), and neurological function was evaluated with FSS and modified Rankin Scale (mRS) scoring criteria. Post-stroke fatigue patients with vitamin D deficiency were divided into two groups: a study group in which patients received vitamin D supplementation (cholecalciferol, 600 IU/day) along with usual care, and a control group in which patients received usual care alone. At the end of 1 and 3 months after treatment, all PSE patients accepted re-measurement of serum vitamin D and re-evaluation of fatigue and neurological function. Results: A total of 532 AIS patients were consecutively recruited to participate in this study. Patients without PSF, non-vitamin D deficiency, pre-stroke fatigue, or vitamin D supplementation were excluded from the study. In addition, patients who were lost to follow-up were also excluded. Finally, 139 out of 532 (26.1%) patients with PSF and vitamin D deficiency received vitamin D supplementation treatment. Fatigue Severity Scale score was significantly lower in the study group than in the control group at 1 month (t = -4.731, p < 0.01) and 3 months (t = -7.937, p < 0.01) after treatment. One month after treatment, mRS score in the study group was lower than that in the control group without statistical difference (t = -0.660, p > 0.05), whereas mRS was significantly higher in the study group than in the control group at 3 months after treatment (t = -4.715, p < 0.01). Conclusions: Our results indicated that vitamin D supplementation could improve fatigue symptoms and neurological outcomes in PSF patients with vitamin D deficiency. Subject to replication in other settings, a randomized controlled trial (RCT) might be undertaken to validate the potential beneficial impact of vitamin D supplementation in post-stroke patients found to be vitamin D deficient.
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In January 2012, a serious accident polluted the Longjiang River with high concentrations of cadmium (Cd) and other concomitant metals and metalloids in the water. After emergency treatment (i.e., the addition of coagulants), these metals and metalloids were transferred from the water into the sediment through precipitation of the flocculent materials produced. In this study, the long-term distribution of six metals and metalloids in the sediment of the Longjiang River was investigated and their ecological risks were assessed. Approximately 1 year after the accident (i.e., late 2012), the average Cd content in the sediment of the affected sites decreased to 25.6 ± 19.5 mg/kg, which was 8 times higher than that of 3.16 ± 3.18 mg/kg in the upstream reference sites. In 2016 and 2017, the average Cd content in the sediment of the affected sites further decreased to 4.91 ± 2.23 and 6.27 ± 4.27 mg/kg, respectively. Compared with late 2012, the amounts of Zn, Pb, and Cu obviously decreased in 2016 and 2017, whereas there were no obvious differences in the As and Hg amounts during 3 years considered. Among metals and metalloids, the average contribution of Cd to the potential ecological risk index (RI) was 90%, 69%, and 70% in the affected areas in 2012, 2016, and 2017, respectively, suggesting that Cd was the most important factor affecting the ecological risk of metals in the Longjiang River. It should be noted that the average contribution of Hg to RI in the affected areas increased from 8% in 2012 to 25% and 23% in 2016 and 2017, respectively. The sequence of contribution of six elements was Cd > Hg > As>Pb > Cu ≈ Zn. A high ecological risk of metals and metalloids was found in the sediments of two reservoirs, probably owing to the barrier effect of the dam. This study will be useful for the environmental management of rivers affected by accidental pollution of metals and metalloids.
Assuntos
Metaloides , Metais Pesados , Poluentes Químicos da Água , Acidentes , China , Monitoramento Ambiental , Sedimentos Geológicos , Metaloides/análise , Metais Pesados/análise , Medição de Risco , Rios , Poluentes Químicos da Água/análiseRESUMO
PURPOSE: The aim of this study was to compare the neuronal firing rate and oscillatory activity of the subthalamic nucleus (STN) between the more affected (MA) and the less affected (LA) hemispheres in Parkinson's disease (PD). PATIENTS AND METHODS: We recorded and analyzed the intra-operative microelectrode recordings (MER) from the STN of 24 PD subjects. Lateralized Unified Parkinson's Disease Rating Scale (UPDRS) III sub-scores (item 20-26) were calculated. The STN corresponding to the MA side was designated as the MA STN while the other side as the LA STN. Single unit characteristics including interspike intervals were identified and spectral analyses were assessed. Further, the mean spontaneous firing rate (MSFR) of neurons was calculated. The correlations between clinical symptoms and neuronal activity were analyzed. RESULTS: The firing rate in the MA and LA sides were 43.18 ± 0.74 Hz and 36.94 ± 1.32 Hz, respectively, with an increase of 16.9% in the MA group. The number of neurons that oscillated in the Tremor-Frequency Band (TFB), ß-Frequency Band (ßFB), and the non-oscillatory cells in the MA group were 43, 115, and 62 versus 78, 68, and 54 in the LA group, respectively. The proportions of the three types of neurons were different between both groups. The firing rate of the STN neurons and the UPDRS III sub-scores were positively correlated. Additionally, we observed a positive correlation between the percentage of ßFB oscillatory neurons and bradykinesia score. CONCLUSION: The firing rate of the STN in the MA hemisphere is higher than in the LA side, following disease progression and there seems to be an increase in firing rate. The ßFB oscillatory neurons are at a larger proportion in the MA group while there were larger percentage of TFB oscillatory cells in the LA group. The proportion of ßFB oscillatory neurons is selectively correlated with the severity of bradykinesia.
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The molecular mechanisms underlying the development of epilepsy, i.e., epileptogenesis, are due to altered expression of a series of genes. Global expression profiling of temporal lobe epilepsy is confounded by a number of factors, including the variability among animal species, animal models, and tissue sampling time-points. In this study, we pooled two microarray datasets of the most used pilocarpine and kainic acid epilepsy models from the Gene Expression Omnibus database. A total of 567 known and novel genes were commonly differentially expressed across the two models. Pathway analyses demonstrated that the dysregulated genes were involved in 46 pathways. Real-time PCR and western blot analysis confirmed the activation of extracellular matrix (ECM)/integrin signaling pathways. Moreover, targeting ECM/integrin signaling inhibits astrocyte activation and promotes neuron injury in the hippocampus of epileptic mice. This study may provide a "gene/pathway database" that with further investigation can determine the mechanisms underlining epileptogenesis and the possible targets for neuron protection in the hippocampus after status epilepticus.
Assuntos
Epilepsia do Lobo Temporal/genética , Proteínas da Matriz Extracelular/genética , Perfilação da Expressão Gênica , Integrinas/genética , Transdução de Sinais/genética , Animais , Bases de Dados Genéticas/estatística & dados numéricos , Epilepsia do Lobo Temporal/induzido quimicamente , Redes Reguladoras de Genes , Hipocampo/metabolismo , Humanos , Ácido Caínico , Masculino , Metanálise como Assunto , Camundongos , Análise em Microsséries , Pilocarpina , RatosRESUMO
Emergent cadmium pollution can cause water quality deterioration in rivers, which destroys the aquatic eco-environment and poses threats to human health. Fish species in these aquatic systems are prone to such pollution incidents and act as important indicators of the pollution level. Because cadmium enters the systematic circulation of fish and is non-biodegradable, the investigation of cadmium accumulation in fish bodies provides insights into the detrimental effects of cadmium pollution on the aquatic biological system. This research aims to validate the eco-environmental risks associated with emergent cadmium pollution incidents based on the investigation of the different tissues and organs of diverse fish species. The investigation was conducted six times along the Longjiang River using sampling methods during which all fish species were also classified and analyzed based on the water layer they reside in and their feeding habits. The results show that the cadmium concentration in the fish tissues is significantly higher in the former three investigations compared with that of the latter three analyses. For herbivorous, carnivorous, and omnivorous fish species, the cadmium concentration of their different tissues and organs follows the order:kidney > liver > gut > gill > egg > scale ≈ muscle. The cadmium concentration in the kidney is significantly higher (P<0.05) than that in any other organs of the fish species. This agrees with the fact that the kidney intensively metabolizes and accumulates heavy metals. The cadmium concentration in the same tissues or organs of the fish species living in different water layers follows the trend:demersal fish species > middle lower-layer species > middle upper-layer species. The sequence of the cadmium bioaccumulation factors in the muscles of different fish species is omnivore > carnivorous > herbivorous, that is, 8.32, 6.33, and 5.15, respectively, while the bioaccumulation factors in the muscles of the fish species in different water layers decrease in the following sequence:demersal fish species (8.18) > middle bottom-layer fish species (7.70) > middle upper-layer fish species (4.99). These experimental results indicate the biomagnification effects in heavy metal-polluted aquatic environments, where the bioaccumulation of heavy metals by fish is related to both the overall pollution level and local residential environment.
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Cádmio/análise , Peixes , Rios , Poluentes Químicos da Água/análise , Animais , China , Monitoramento Ambiental , Metais PesadosRESUMO
RATIONALE: Autonomic symptoms are not uncommon in chronic inflammatory demyelinating polyneuropathy (CIDP), but they are mostly mild and transient and are overshadowed by somatic manifestations. Here, we report a very unusual case of CIDP with severe autonomic symptom, intestinal obstruction, as initial and persistent symptom which responded well to high-dose glucocorticoid and intravenous immunoglobulin treatment. PATIENT CONCERNS: We described a patient with CIDP with precedent and long-lasting incomplete intestinal obstruction. Clinical manifestations were precedent and chronic abdominal pain, distension and constipation, and later numbness and weakness of lower and upper limbs. Radiograph showed incomplete intestinal obstruction, cerebrospinal fluid (CSF) showed albuminocytological dissociation and electromyography indicated neurogenic lesion. DIAGNOSES: CIDP with incomplete intestinal obstruction was diagnosed based on the history, related symptoms, typical abdominal radiograph, CSF albuminocytological dissociation, and electromyographic findings. INTERVENTIONS: The patient was treated with intravenous methylprednisolone and immunoglobulin. OUTCOMES: After treatment, the intestinal obstruction disappeared and the somato-symptoms improved greatly and gradually. LESSONS: This case highlights the need for diagnostic vigilance in cases of incomplete intestinal obstruction of unknown cause. We recommend CSF and electromyography examination in view of rare but possibility of CIDP.
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Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Obstrução Intestinal/terapia , Pessoa de Meia-Idade , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapiaRESUMO
During typhoon "Mujigae" in October 2015, water samples and surface sediments were collected from Gaozhou Reservoir, a drinking water reservoir, for simulation and analysis of the kinetics of suspended solids adsorption to nitrogen and phosphorus and the adsorption isotherms of suspended solids with different particle sizes and different concentrations. The results showed no obvious nitrogen adsorption of suspended solids of Gaozhou Reservoir. However, the adsorption effect to phosphorus by suspended solids was significant and the equilibrium time of phosphorus adsorption was 10 hours. The adsorption capacity of phosphorus increased with the decrease of sediment particle size when particle sizes were less than 0.25 mm, whereas it increased with the increase of suspended solids concentration when the concentration was in the range of 0.2-2.0 kg·m-3. The adsorption isotherm of suspended solids to phosphorus conformed to the Langmuir and Freundlich models, and the maximum adsorption capacity increased with the decrease of suspended solids particle sizes, which increased with the increase of suspended solids concentrations. The maximum adsorption capacity of suspended solids to phosphorus was 0.073-1.776 mg·g-1. These results indicated that the increase of suspended solids concentration due to the heavy rainfall of the typhoon promoted the adsorption of suspended solids to phosphorus, which reduced eutrophication in Gaozhou Reservoir.
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Água Potável/química , Nitrogênio/química , Fósforo/química , Poluentes Químicos da Água/química , Adsorção , China , Tempestades Ciclônicas , Sedimentos Geológicos , ChuvaRESUMO
In early January 2012, the Longjiang River was subjected to a serious cadmium (Cd) pollution accident, which led to negatively environmental and social impacts. A series of measures of emergency treatment were subsequently taken to reduce water Cd level. However, little information was available about the change of Cd level in environmental matrices and long-term effect of this pollution accident to aquatic ecosystem. Thus, this study investigated the distribution of Cd in water and sediment of this river for two years since pollution accident, as well as assessed its ecological risk to aquatic ecosystem of Longjiang River. The results showed that it was efficient for taking emergency treatment measures to decrease water Cd concentration to below the threshold value of national drinking water quality standard of China. There was high risk (HQ > 1) to aquatic ecosystem in some of reaches between February and July 2012, but low or no risk (HQ < 1) between December 2012 to December 2013. Cd concentration in sediment in polluted reaches increased after pollution accident and emergency treatments in 2012, but decreased in 2013. During flood period, the sediment containing high concentration of Cd in Longjiang River was migrated to downstream Liujiang River. Cd content in sediment was reduced to background level after two years of the pollution accident occurrence. The study provides basic information about Cd levels in different media after pollution accident, which is helpful in evaluating the effectiveness of emergency treatments and the variation of ecological risk, as well as in conducting water management and conservation.
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Cádmio/análise , Sedimentos Geológicos/química , Rios/química , Poluentes Químicos da Água/análise , Qualidade da Água , Acidentes , China , Ecossistema , Monitoramento Ambiental , Metais Pesados/análise , Medição de RiscoRESUMO
Temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy, characterized by hippocampal neuron damage and hippocampal sclerosis. Long noncoding RNAs (lncRNAs) have been increasingly recognized as posttranscriptional regulators. However, their expression levels and functions in TLE remain largely unknown. In the present study, TLE rat model is used to explore the expression profiles of lncRNAs in the hippocampus of epileptic rats using microarray analysis. Our results demonstrate that H19 is the most pronouncedly differentiated lncRNA, significantly upregulated in the latent period of TLE. Moreover, the in vivo studies using gain- and loss-of-function approaches reveal that the overexpression of H19 aggravates SE-induced neuron apoptosis in the hippocampus, while inhibition of H19 protects the rats from SE-induced cellular injury. Finally, we show that H19 might function as a competing endogenous RNA to sponge microRNA let-7b in the regulation of cellular apoptosis. Overall, our study reveals a novel lncRNA H19-mediated mechanism in seizure-induced neural damage and provides a new target in developing lncRNA-based strategies to reduce seizure-induced brain injury.
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Apoptose/genética , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neurônios/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Sequência de Bases , Modelos Animais de Doenças , Regulação da Expressão Gênica , Masculino , MicroRNAs , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Estado Epiléptico/genética , Estado Epiléptico/patologiaRESUMO
INTRODUCTION/AIM: To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). METHODS: Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis. RESULTS: Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36-0.57, p < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64-0.82, p < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] -1.13; 95% CI -1.68 to -0.58, p < 0.0001; BMI: MD -0.42; 95% CI -0.71 to -0.14, p = 0.004; fasting insulin: MD -2.44; 95% CI -3.79 to -1.09, p = 0.0004; and 2 h insulin: MD -8.26; 95% CI -8.47 to -8.05, p < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42-0.69, p < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41-0.73, p < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD -1.45; 95% CI -2.11 to -0.79, p < 0.0001) and BMI levels (MD -1.12; 95% CI -2.00 to -0.24, p < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. CONCLUSIONS: The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312.
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Medicamentos de Ervas Chinesas/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
BACKGROUND: Diabetic kidney disease (DKD) is a serious complication associated with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) is widely used in China to treat DKD, and in particular microalbuminuria and macroalbuminuria. This study will address the efficacy and safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients with macroalbuminuria. METHODS/DESIGN: This study is a 24-week, randomized, multi-center, double-blinded, double-dummy, controlled, clinical trial that will include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24-h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) ≤ 133 µmol/L (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to week 24 will represent the primary endpoint with secondary endpoints including SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin excretion rate (UAER), etc. Safety assessments will also be evaluated. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of SZF relative to irbesartan in the treatment of DKD patients with macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311 . Registered on 15 April 2015.
Assuntos
Albuminúria/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Irbesartana/uso terapêutico , Rim/efeitos dos fármacos , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Albuminúria/urina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Biomarcadores/sangue , China , Creatinina/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/urina , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Irbesartana/efeitos adversos , Rim/fisiopatologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Early interventions in prediabetes can prevent or delay the incidence of type 2 diabetes mellitus (T2DM). The aim of this review was to assess the efficacy and safety of traditional Chinese patent medicine (TCPM) on the prevention of T2DM. METHODS: Seven electronic databases were searched to identify eligible trials published until June 1, 2016. Randomized controlled trials (RCTs) that compared TCPM plus lifestyle modification (LM) versus LM alone were included for in the. RCTs that used TCPM plus LM compared with placebo plus LM were also included. Methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. A random- or fixed-effect model was used to analyze outcomes that were expressed as risk ratios (RRs) or mean differences (MD), and the I2 statistic was used to assess heterogeneity. RESULTS: Twenty-six trials with a total of 4169 participants met the inclusion criteria. Subgroup analysis confirmed that, compared with LM alone, TCPM and LM together were significantly better at reducing diabetes (RR, 0.47; 95% CI, 0.38-0.59) and normalizing blood glucose (RR, 0.76; 95% CI, 0.69-0.85). They also caused a greater reduction in fasting plasma glucose (FBG) (MD, -0.37; 95% CI, -0.62 to -0.13), 2-h plasma glucose (2h PG) (MD, -0.91; 95% CI, -1.35 to -0.47) and body mass index (BMI) (MD, -0.45; 95% CI, -0.76 to -0.14). Compared with placebo plus LM, TCPM plus LM was superior at reducing diabetes (RR, 0.55; 95% CI, 0.45-0.68) and normalizing blood glucose (RR, 0.62; 95% CI, 0.50-0.76). The interventions were also associated with a decline in FBG levels (MD, -0.68; 95% CI, -1.25 to -0.11) and 2h PG levels (MD, -1.07; 95% CI, -1.85 to -0.29). There were no significant differences in adverse events in either group. Subgroup and sensitivity analyses found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. Generally, the quality of evidence was low for the effect of TCPM on the incidence of diabetes and normalization of blood glucose, and was very low for the effects of TCPM on FBG, 2h PG, and BMI. CONCLUSIONS: Based on this systematic review, TCPM may reduce the risk of progression to T2DM and increase the possibility of regression toward normoglycemia. As a result of the methodological drawbacks of the included studies, more rigorously designed RCTs are required to more reliably assess the efficacy of TCPM and long-term follow-up is needed before TCPM can be recommended for prediabetic patients.
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Medicina Tradicional Chinesa/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , HumanosRESUMO
Large-scale cyanobacteria bloom occurred in the summer of 2014 in the Guishi Reservoir that is an important drinking water source for Hezhou City. The dynamic change regularity, external pollution sources, and the phytoplankton community characteristics during the bloom were investigated to evaluate the eutrophication in the reservoir and to present effective prevention and control measures. The results showed that nitrogen and phosphorus concentrations increased year by year; water quality on some sites has been out of class â ¡ of national water quality standards; and the main pollution source was the agricultural non-point sources. Phytoplankton cell density was in the range of 8.60×106-5.36×108 cells·L-1 and chlorophyll a concentrations reached 74.48 µg·L-1 during the bloom. The dominant species was Microcystis wesenbergii whose density reached 5.36×108 cells·L-1. The cell density decreased over time and concentrated on the surface and at the depth of 2 m underwater. The total phytoplankton cell density was strongly correlated to total phosphorus, total nitrogen, nitrate nitrogen, and the permanganate index, and was inversely correlated to transparency. The water in the Guishi Reservoir was not polluted by microcystic toxins. Moreover, Guishi Reservoir is in a meso-eutrophic state; therefore, the prevention and control of the cyanobacteria bloom should focus on weather conditions and on reducing the input of nitrogen and phosphorus to keep the nutrient levels low.
Assuntos
Cianobactérias/crescimento & desenvolvimento , Água Potável/microbiologia , Eutrofização , Fitoplâncton/crescimento & desenvolvimento , China , Clorofila A/análise , Nitrogênio/análise , Fósforo/análise , Estações do AnoRESUMO
To study the distribution of phytoplankton and water quality of Beijiang River, the community structure of phytoplankton was investigated and analyzed in wet and dry seasons. The results showed that a total of 74 species belonging to six phyla, 29 family and 48 genera of phytoplankton were identified, including 58 species of five phyla, 23 family and 41 genera in wet season and 59 species of six phyla, 26 family and 40 genera in dry season. Phytoplankton community structure in Beijiang River was represented by Bacillariophyta, Chlorophyta and Cyanophyta. Bacillariophyta dominanted the phytoplankton, and the dominant species were Aulacoseira granulate, Fragilaria virescens, Surirella biseriata, Nitzschia amphibia, Navicula simplex, Cyclotella meneghiniana, Synedra ulna, Gomphonema angustatum and Cymbella tumida. There was little difference in phytoplankton density between both seasons with the mean values being 3.54 x 10(5) and 4.87 x 10(5) cells L(-1) in dry and wet seasons, respectively. Based on the RDA results, DO, permanganate index, nitrogen and phosphorus were the important environmental factors affecting the distribution of phytoplankton in Beijiang River. The water quality of Beijiang River was classified as oligo-mesotrophic level even if this river was subjected to nitrogen and phosphorus pollution mainly from agricultural non-point source.