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ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) is one of the main cardiovascular diseases (CVDs) leading to an increase in global mortality, and its key pathological features are lipid accumulation and oxidative stress. Huang-Lian-Jie-Du decoction (HLJDD), a representative formula for clearing heat and detoxifying, has been shown to reduce aortic lipid plaque and improve AS. However, multiple components and multiple targets of HLJDD pose a challenge in comprehending its comprehensive mechanism in the treatment of AS. AIM OF THE STUDY: This study was designed to illustrate the anti-AS mechanisms of HLJDD in an apolipoprotein E-deficient (ApoE-/-) mouse model from a metabolic perspective. MATERIALS AND METHODS: ApoE-/- mice were kept on a high-fat diet (HFD) to induce AS. Serum total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were determined to evaluate the influence of HLJDD on dyslipidemia. Oil red O was used to stain mouse aortic lipid plaques, and hematoxylin and eosin (HE) staining was used to assess the pathological changes in the aortic roots. Metabolomics and lipidomics combined with serum pharmacochemistry were performed to research the HLJDD mechanism of alleviating AS. RESULTS: In this study, HLJDD treatment improved serum biochemical levels and histopathological conditions in AS mice. A total of 6 metabolic pathways (arginine biosynthesis, glycerophospholipid, sphingolipid, arachidonic acid, linoleic acid, and glycerolipid metabolism) related to 25 metabolic biomarkers and 41 lipid biomarkers were clarified, and 22 prototype components migrating to blood were identified after oral administration of HLJDD. CONCLUSION: HLJDD improved AS induced by HFD in ApoE-/- mice. The effects of HLJDD were mainly attributed to regulating lipid metabolism by regulating the metabolic pathways of glycerophospholipids, sphingolipids, arachidonic acid, linoleic acid, and glycerolipids and reducing the levels of oxidative stress by upregulating arginine biosynthesis.
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Aterosclerose , Medicamentos de Ervas Chinesas , Camundongos , Animais , Lipidômica , Ácido Araquidônico , Ácido Linoleico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Aterosclerose/tratamento farmacológico , Apolipoproteínas E/genética , Biomarcadores , Colesterol , ArgininaRESUMO
Yak milk is essential to maintain the normal physiological functions of herders in Tibetan areas of China. However, the lipid components of yak colostrum (YC) and mature milk (YM) have not been systematically studied. We employed a quantitative lipidomics to comprehensively describe the alterations in the milk lipid profile of lactating yaks. Herein, totally 851 lipids from 28 lipid subclasses in YC and YM were identified and screened for 43 significantly different lipids (SDLs; variable importance in projection > 1, fold change < 0.5 or > 2 with P < 0.05), with cholesterol ester (CE, 16:0) and triacylglycerol (TAG, 54:6 (20:5), 50:1 (16:0), 56:6 (20:5)) were the potential lipid biomarkers. Fourteen SDLs were modulated downwards, and 29 SDLs were modulated upwards in YM. Moreover, by analyzing lipid metabolic pathways in these SDLs, glycerophospholipid metabolism was the most critical. Our results furnish integral lipid details for evaluating yak milk's nutritional quality.
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Colostro , Leite , Gravidez , Feminino , Animais , Bovinos , Colostro/metabolismo , Lactação/metabolismo , Lipidômica/métodos , Cromatografia Líquida de Alta Pressão , Triglicerídeos/metabolismoRESUMO
Objective: This study aimed to assess the relationship between glucocorticoid treatment and mortality among patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: We conducted a retrospective, hospital-based cohort study from 2019 to 2022, including 394 consecutively enrolled HBV-ACLF patients at the Third Affiliated Hospital of Chongqing Medical University. We recorded patient demographics, liver function, CD163 concentration, Model for End-Stage Liver Disease (MELD) score, and complications. The primary endpoint was 30-day mortality. Results: No significant differences were observed between the glucocorticoid-treated and non-glucocorticoid groups regarding sex, age, liver function, complications, or plasma CD163 concentration. After treatment, the median levels of total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), and HBV DNA were 322.9 (IQR 258.6-383.3) µmol/L, 354.4 (IQR 253.1-444.6) U/L, 258.4 (IQR 186.4-322.4) U/L, 2.3 (IQR 2.1-2.5), and 5.0 (IQR 4.0-6.0) log IU/mL, respectively. Changes in ALT, AST, sCD163, TBil, INR, and MELD score before and after treatment showed no statistical differences between the glucocorticoid and non-glucocorticoid groups (P > .05). However, the mortality rate was significantly lower in the glucocorticoid group compared to the non-glucocorticoid group (11.2% vs. 29.9%, respectively; P < .001). Multivariable analysis revealed that, after adjusting for confounders, non-glucocorticoid treatment was associated with a higher adjusted hazard ratio (HR) for mortality (HR = 3.7, 95% CI 2.2-6.2) compared to glucocorticoid treatment. Additionally, an interaction test indicated that the association between non-glucocorticoid treatment and mortality was more robust in the sCD163 ≥ 18.2 mg/L group (HR = 7.6, 95% CI 2.9-19.9) but weaker in the sCD163 < 18.2 mg/L group (HR = 2.2, 95% CI 1.2-4.3) (P for interaction < .05). Conclusions: These findings suggest that glucocorticoids are an effective treatment for reducing mortality in HBV-ACLF patients, with particular effectiveness observed in patients with high sCD163 concentrations.
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Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Humanos , Vírus da Hepatite B , Glucocorticoides/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Doença Hepática Terminal/complicações , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Insuficiência Hepática Crônica Agudizada/etiologia , Prognóstico , Índice de Gravidade de DoençaRESUMO
Kashin-Beck disease (KBD) is a nutrition-related osteoarthropathy, and selenium (Se) deficiency is an environmental risk factor for KBD. Notch/Hes1 signaling pathway plays a vital role in regulating cartilage, but its exact mechanisms in KBD remain unknown. The Se contents were determined using the hydride atomic fluorescence spectrometry assay technique, and the mRNA levels were detected via quantitative real-time PCR. The chondrocyte injury models were established by Se deficiency and tert-butyl hydroperoxide (tBHP), respectively; apoptosis and necrosis rates were detected using Hoechst 33,342/PI and Annexin V-FITC/PI. The results showed that the Se levels in the flour of KBD areas were lower than that of the non-KBD areas, and the Se levels in the plasma of KBD patients were lower than that of the controls. The expressions of Notch1, Jagged1, and Hes1 were higher in the whole blood of KBD patients than those of the controls, and Notch1 was negatively correlated with the expression of BCL2, while was positively correlated with BAX. In injury, chondrocytes induced by low Se and tBHP, the expression of Notch1, Jagged1, and Hes1 increased, apoptosis and necrosis rates increased in Se deficiency and tBHP groups, while Se supplementation reversed it. Decreased plasma Se in KBD patients may be related to low dietary Se. Se deficiency might be involved in the pathological process of KBD by activating the Notch/Hes1 signaling pathway to induce excessive apoptosis of chondrocytes, the activation of Notch/Hes1 promotes oxidative injury, and Se supplementation could reverse it. The importance of Notch/Hes1 signaling pathway in KBD development will provide a new potential target for KBD.
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Doença de Kashin-Bek , Selênio , Humanos , Cartilagem/metabolismo , Cartilagem/patologia , Doença de Kashin-Bek/metabolismo , Necrose , Selênio/deficiência , Selênio/metabolismo , Selênio/farmacologia , Transdução de Sinais , Fatores de Transcrição HES-1/metabolismo , Receptores NotchRESUMO
Protective autophagy can be activated by external stimuli such as chemotherapy (CT) and photothermal therapy (PTT), leading to tumour resistance. As a key subcellular for autophagy, lysosomal dysfunction is crucial for autophagy suppression. Furthermore, lysosomal drug sequestration enhances basic drug resistance such as doxorubicin (DOX), which is trapped away from its target site, namely, the nucleus. Moreover, most of nanodrug delivery systems are internalised to lysosome for degradation, which further leads to DOX resistance. Lysosome serves as an essential organelle in drug resistance mechanisms, whose acidification arrest provides a potential strategy to inhibit autophagy and lysosomal drug sequestration simultaneously. The chloride channel-3 (ClC-3) protein is known as an important Cl--H+ transporter to maintain lysosomal pH at low values of various human cells. Herein, a black phosphorus-based theranostic nanoplatform of BP-A-S@D is constructed, and HeLa cells are used as a model to verify the effect of ClC-3 on tumour lysosomal acidification and autophagy regulation. Consequently, ClC-3 silencing inhibits not only protective autophagy to sensitise chemo-photothermal therapy, but also DOX resistance by suppressing lysosomal acidification. Therefore, ClC-3 silencing could simultaneously inhibit autophagy and lysosomal drug sequestration to improve anti-tumour efficiency.
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Canais de Cloreto , Terapia Fototérmica , Humanos , Autofagia , Canais de Cloreto/genética , Doxorrubicina/farmacologia , Doxorrubicina/metabolismo , Células HeLa , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , FototerapiaRESUMO
Previous works imply that involving brainstem in neuropathological studies of Alzheimer's disease (AD) is of clinically significant. This work constructs a comprehensive neural mass model for cholinergic neuropathogenesis that involves brainstem, thalamus and cortex, wherein how acetylcholine deficiency in AD affects neural oscillation of the model output is systematically explored from the perspective of neurocomputation. By decreasing synapse connectivity parameters in direct cholinergic pathway from brainstem to thalamus or in indirect glutamatergic synapse pathway from cortex to brainstem to mimic the pathological condition of reduced acetylcholine release in patients with AD, the property of neural oscillation in this model is numerically investigated by means of power spectrum in frequency domain and amplitude distribution in time domain. Simulated results demonstrate that decreasing synapse connectivity whether in the direct cholinergic pathway or in the indirect glutamatergic synapse pathway can alter the neural oscillation significantly in three aspects: it induces an obvious decrease of dominant frequency; it leads to a degraded rhythmic activity in the alpha frequency band as well as an enhanced rhythmic activity in the theta frequency band; it results in reduced oscillation amplitude of the model output. These results are agreement with the characteristic of electrophysiological EEG measurement recorded in AD, especially support the hypothesis that cholinergic deficiency is a promising pathophysiological origin of EEG slowing in AD. Our analysis indicates that targeting the cholinergic system may have potential prospects in early diagnosis and treatment of AD.
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Doença de Alzheimer , Acetilcolina , Doença de Alzheimer/patologia , Tronco Encefálico/patologia , Colinérgicos , Eletroencefalografia , Humanos , Tálamo/fisiologiaRESUMO
Ecological ditches and bioretention ponds have received widespread attention and application due to their runoff pollution control capabilities and ecological benefits. However, a single ecological ditch or bioretention pond often has problems, such as unstable nitrogen and phosphorus removal and substrate clogging in rural runoff pollution control. Thus, we connected the two facilities in a series to construct a combined system, using the ecological ditch to pretreat, therefore reducing the pollution load of the bioretention pond and mitigating substrate clogging. At the same time, the submerged area was set and an external natural carrier carbon source was added in the bioretention pond to improve the nitrogen removal. The effects of the carrier carbon source, rainfall intensity, and alternating wet and dry conditions on the control of rural runoff pollution by the combined system were explored. The results showed that adding straw and sawdust as carrier carbon sources could increase the TN removal of the bioretention pond by 19.9% and 20.4%, respectively. When the simulated rainfall intensity increased from light rain to heavy rain, the removal efficiencies of COD, NH4+-N, TN, and TP in the combined system with external carbon source decreased by 17.0%, 16.8%, 20.4%, and 17.2% on average, respectively. The contribution of the ecological ditch to the removal of the four pollutants decreased by 16.3%, 13.0%, 24.2%, and 22.1% on average. Alternating dry and wet operation can improve the pollutant removal. Compared with continuous inflow, the average TN removal of the sawdust group increased by 12.3% after three weeks of drought. The results of microbial community analysis showed that the α-diversity of the bioretention pond in the sawdust group and the straw group was higher than that in control group. The abundance of Thiobacillus was significantly higher in the submerged area of bioretention ponds with carbon sources than that in the control group. These research results are expected to provide technical support for the practical application of the combined system.
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Lagoas , Chuva , Carbono , Nitrogênio , FósforoRESUMO
Objective: To research the molecular mechanism of compound Danshen tablets in the treatment of hepatic fibrosis through network pharmacology. Methods: Traditional Chinese medicine systems pharmacology (TCMSP) and online Mendelian inheritance in man (OMIM) databases were searched for compound Danshen tablets' active ingredients o and hepatic fibrosis-related genes. The network enrichment of the targets of "herb-compound-target" was visualized and analyzed using Cytoscape software. Then, the screened target genes were used to construct a protein-protein interaction network. The DAVID enrichment database (the database for annotation, visualization, and integrated discovery) was adopted for GO (Gene Ontology) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment of vital nodes. Results: The results yielded 234 targets of compound Danshen tablets; ten important targets (TNF, IL-10, TGF-ß1, EGF, CXCL16, CCL21, SERPINB5, SERPINA1, SOD2, and PPIG) for reversing hepatic fibrosis; and four core targets (TNF, IL-10, TGF-1, and EGF). In addition, KEGG enrichment analysis showed that compound Danshen tablets mainly involved FoxO and MAPK signaling pathways, as the key signaling pathways in the treatment of hepatic fibrosis. Conclusion: TNF, IL-10, TGF-1, and EGF and FOXO and MAPK signaling pathways play a key role in the pathogenesis of hepatic fibrosis. Based on the results of this study, the mechanism of action of compound Danshen tablets in the treatment of hepatic fibrosis may be associated with the regulation of FoxO and MAPK signaling pathways and inhibition of TNF, IL-10, TGF-1, and EGF.
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BACKGROUND: Little is known about how cyberbullying victimization may influence adolescent nonsuicidal self-injury (NSSI) and what conditions may buffer the detrimental effects of cyberbullying victimization. By integrating multiple theories, this study investigated emotion reactivity as an underlying mediator and mindfulness as a potential moderator to explain the link between cyberbullying victimization and NSSI among Chinese adolescents. METHOD: A total of 2,523 participants with an age range of 11 to 16 years old (Mage = 13.22, SD = 1.60, 48.4% girls) completed assessments. RESULTS: After controlling SES, age, gender, traditional bullying victimization, and child maltreatment, latent moderated structural equation modeling revealed that emotion reactivity mediated the association between cyberbullying victimization and NSSI. In addition, dispositional mindfulness was found to buffer the relation between cyberbullying victimization and NSSI, but not the relation between cyberbullying victimization and emotion reactivity. LIMITATIONS: This study was cross-sectional in nature and relied exclusively upon self-report measures. CONCLUSIONS: The findings provide researchers and practitioners with a deeper understanding of the relation between cyberbullying victimization and NSSI among adolescents and its underlying mechanism. Suggested intervention and prevention strategies include helping youth reduce emotion reactivity to break the cyberbullying victimization to NSSI cycle and to enhance youths' mindfulness to buffer against the ill effects of cyberbullying victimization.
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Bullying , Vítimas de Crime , Cyberbullying , Atenção Plena , Comportamento Autodestrutivo , Adolescente , Criança , Estudos Transversais , Emoções , Feminino , Humanos , MasculinoRESUMO
The present paper aimed to investigate the roles of quinones contained in wastewater and the enhanced effects on microbial fuel cells (MFCs) under different redox conditions. The feasibility of using wastewater rich in quinones to act as co-substrate and redox mediators (RMs) library to strengthen the synergistic removal of azo dye in MFCs was evaluated. The results demonstrated that quinones achieved enhanced effects on electricity generation and COD removal of MFC better at higher current intensity. The addition of pure quinone decreased electron transfer resistance (Rct) of MFCs from 4.76 Ω to 2.13 Ω under 1000 Ω resistance and 1.16 Ω-0.75 Ω under 50 Ω resistance. Meanwhile, higher coulombic efficiency was achieved. Compared with sodium acetate, using quinone-rich traditional Chinese medicine (TCM) wastewater as the co-substrate enhanced the synergistic removal of reactive red 2 (RR2) in MFCs from 79.58% to 92.45% during 24 h. RR2 was also degraded more thoroughly due to the accelerated electron transfer process mediated by RMs. Microbial community analysis demonstrated that the presence of quinone in TCM wastewater can enrich different exoelectrogens under varied redox conditions and thus influenced the enhanced effects on MFC. Metagenomic functional prediction results further indicated that the abundance of functional genes involved in carbohydrate metabolism, membrane transport metabolism, biofilm formation, and stress tolerance increased significantly in presence of RMs. Redundancy analyses revealed that RMs addition was the more important factor driving the variation of the microorganism community. This study revealed the potential effect of quinones as redox mediators on the bioelectrochemical system for pollutants removal.
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Fontes de Energia Bioelétrica , Compostos Azo , Eletricidade , Eletrodos , Oxirredução , Quinonas , Águas ResiduáriasRESUMO
Kashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy related to selenium (Se) deficiency. Se participates in the synthesis of selenoprotein in the form of selenocysteine. In total, 25 selenoproteins, encoded by 25 genes, are currently found in humans; however, the effects of selenoprotein genes on chondrocyte apoptosis, particularly in apoptosis-related genes, remain poorly elucidated. Therefore, in the current study, the expression of selenoprotein genes and apoptosis-related genes were determined by RT-qPCR in patients and chondrocytes and the correlations between them were analyzed using Pearson and Spearman's rank correlation, and the chondrocyte apoptosis rate was detected by Annexin V-FITC/PI. The results showed that the mRNA levels of 17 selenoprotein genes were downregulated, whereas two genes were upregulated in patients with KBD. The BAX/BCL2 ratio and the mRNA levels of BAX and P53 were increased, but the mRNA levels of BCL2 and NF-κB p65 were decreased in patients with KBD. The mRNA levels of GPX2, GPX3, DIO1, TXNRD1, TXNRD3, and SPS2 were most closely associated with apoptosis-related genes in patients with KBD. Moreover, in the Se deficiency group, the mRNA levels of GPX3, DIO1, and TXNRD1 were downregulated and GPX activity was decreased, but the late apoptosis rate, the mRNA levels of BAX and P53, and the BAX/BCL2 ratio were increased; the opposite trend was observed in the Se supplement group. Collectively, these results indicate that selenoprotein transcription profile is dysregulated in patients with KBD. Furthermore, the expression of GPX3, DIO1, and TXNRD1 genes might be involved in the development of chondrocyte apoptosis by affecting antioxidant capacity.
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Doença de Kashin-Bek , Selênio , Apoptose/genética , Condrócitos/metabolismo , Humanos , Doença de Kashin-Bek/genética , Doença de Kashin-Bek/metabolismo , Selênio/farmacologia , Selenoproteínas/genética , Selenoproteínas/metabolismoRESUMO
BACKGROUND: Tingli Dazao Xiefei decoction (TDXD) has been shown to have a therapeutic effect on heart failure (HF). Nevertheless, its molecular mechanism for treating HF is still unclear. MATERIALS AND METHODS: TDXD and HF targets were collected from the databases, and protein-protein interaction (PPI) analysis and enrichment analysis were performed on the overlapping targets. Then, AutoDock was employed for molecular docking. Finally, we used the left anterior descending coronary artery (LAD) ligation to induce HF model rats for in vivo experiments and verified the effect and mechanism of TDXD on HF. RESULTS: Network pharmacological analysis showed that the main active components of TDXD in treating HF were quercetin, kaempferol, beta-carotene, isorhamnetin, and beta-sitosterol, and the core targets were IL-6, VEGFA, TNF, AKT1, and MAPK1. Multiple gene functions and signaling pathways were obtained by enrichment analysis, among which inflammation-related, PI3K/Akt, and MAPK signaling pathways were closely related to HF. Furthermore, the molecular docking results showed that the core targets had good binding ability with the main active components. Animal experiments showed that TDXD could effectively improve left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS), decrease left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs), reduce the area of myocardial fibrosis, and decrease serum BNP, LDH, CK-MB, IL-6, IL-1ß, and TNF-α levels in HF rats. Meanwhile, TDXD could upregulate the expression of Bcl-2, downregulate the expression of Bax, and reduce cardiomyocyte apoptosis. At the same time, it was verified that TDXD could significantly decrease the expression of PI3K, P-Akt, and P-MAPK. Captopril showed similar effects. CONCLUSIONS: Combining network pharmacological analysis and experimental validation, this study verified that TDXD could improve cardiac function and protect against cardiac injury by inhibiting the activation of PI3K/Akt and MAPK signaling pathways.
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Background Exploring potential therapeutic target is of great significance for myocardial infarction (MI) and post-MI heart failure. Transcription factor Yin-Yang 1 (YY1) is an essential regulator of apoptosis and angiogenesis, but its role in MI is unclear. Methods and Results The expression of YY1 was assessed in the C57BL/6J mouse heart following MI. Overexpression or silencing of YY1 in the mouse heart was achieved by adeno-associated virus 9 injection. The survival, cardiac function, and scar size, as well as the apoptosis, angiogenesis, cardiac fibrosis, T helper 2 lymphocyte cytokine production, and macrophage polarization were assessed. The effects of YY1 on Akt phosphorylation and vascular endothelial growth factor production were also investigated. The expression of YY1 in heart was significantly stimulated by MI. The survival rate, cardiac function, scar size, and left ventricular volume of mice were improved by YY1 overexpression but worsened by YY1 silencing. YY1 alleviated cardiac apoptosis and fibrosis, promoted angiogenesis, T helper 2 cytokine production, and M2 macrophage polarization in the post-MI heart, it also enhanced the tube formation and migration ability of endothelial cells. Enhanced Akt phosphorylation, along with the increased vascular endothelial growth factor levels were observed in presence of YY1 overexpression. Conclusions YY1 ameliorates cardiac injury and remodeling after MI by repressing cardiomyocyte apoptosis and boosting angiogenesis, which might be ascribed to the enhancement of Akt phosphorylation and the subsequent vascular endothelial growth factor up-regulation. Increased T helper 2 cytokine production and M2 macrophage polarization may also be involved in YY1's cardioprotective effects. These findings supported YY1 as a potential target for therapeutic investigation of MI.
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Traumatismos Cardíacos , Infarto do Miocárdio , Animais , Apoptose , Cicatriz , Citocinas , Modelos Animais de Doenças , Células Endoteliais , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/prevenção & controle , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-akt , Fator A de Crescimento do Endotélio Vascular , Remodelação Ventricular , Yin-YangRESUMO
BACKGROUND: In patients with acute myocardial infarction (AMI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We performed a protocol for systematic review and meta-analysis to investigate the effect of systemic therapeutic hypothermia in patients with AMI receiving PCI. METHODS: This study will use the Cochrane Library, Web of Science, PubMed, Embase, Allied and Complementary Medicine Database, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and Ongoing Clinical Trials Database. The search terms were hypothermia, cooling, myocardial infarction, myocardial ischemia and acute coronary syndrome. Quality assessment of the included studies was evaluated using the Cochrane risk of bias assessment tool. Statistical analyses were performed using RevMan 5.4 software. RESULTS: The findings of this study will be submitted to peer-reviewed journals for publication. CONCLUSION: This systematic review will provide evidence to determine whether hypothermia therapy is an effective and safe intervention for patients with AMI receiving PCI.Registration number: 10.17605/OSF.IO/9XJSB.
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Hipotermia Induzida , Infarto do Miocárdio/terapia , Humanos , Metanálise como Assunto , Intervenção Coronária Percutânea , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Excessive activation of the nod-like receptor family pyrin domain containing 3(NLRP3) inflammasome plays a significant role in the progression of cardiac injury. In China, it has been well recognized that Chinese herbal medicine is markedly effective in treating cardiovascular diseases (CVDs). LuQi Formula (LQF) has been used clinically for more than 10 years and confirmed to be effective in improving cardiac function and inhibiting apoptosis. However, the specific mechanisms underlying its efficacy are mostly unknown. This study aimed to evaluate whether LQF could alleviate cardiac injury and apoptosis by regulating the NLRP3 inflammasome and the caspase-3/Bax pathway. PURPOSE: In this study, we investigated the effects of LQF on cardiac remodeling in a mouse model of myocardial infarction (MI) in vivo. METHODS: Forty male C57BL/6 mice were randomly divided into four groups: the sham group, the model group, the LQF group, and the perindopril group, with a sample size (n) of 10 mice in each group. Except the sham group, the other groups received left anterior descending (LAD) coronary artery ligation to induce MI and then treated with LQF, perindopril, or saline. Six weeks after MI, echocardiography was used to evaluate cardiac structure and function. Myocardial tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. Myocardial hypertrophy was observed by fluorescent wheat germ agglutinin (WGA) staining. The expressions of NLRP3, ASC, Cle-caspase-1, IL-1ß, TXNIP, Cle-caspase-3, Bcl-2, and Bax in heart tissues were assessed by western blot analysis. mRNA expressions of ANP and BNP in heart tissues were measured by RT-PCR. The expression of reactive oxygen species in myocardial tissue was detected by using a DCFH-DA probe. RESULTS: Echocardiographic analysis showed that compared with the model group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the LQF and perindopril group were increased (P < 0.05), left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end-systole (LVIDs) were reduced (P < 0.05), and H&E and Masson's trichrome staining of cardiac tissues showed that LQF and perindopril could partially reverse ventricular remodeling and alleviate myocardial fibrosis (P < 0.05). WGA fluorescence results showed that compared with the model group, myocardial hypertrophy was significantly reduced in the LQF and perindopril group. We also found that LQF and perindopril reduce the oxidative stress response in the heart of MI mice. The protein expression of NLRP3, ASC, Cle-caspase-1, IL-1ß, TXNIP, Cle-caspase-3, and Bax was downregulated in the LHF and perindopril treatment group, and Bcl-2 expression was upregulated. CONCLUSION: LQF and perindopril significantly attenuated cardiac injury and apoptosis in the MI model. In addition, we found that LQF effectively inhibited the activation of the NLRP3/ASC/caspase-1/IL-1ß cascade, decreased inflammatory infiltration, delayed ventricular remodeling, and downregulated caspase-3/Bax signaling, which can effectively reduce the apoptosis of cardiomyocytes. Perindopril showed the same mechanism.
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BACKGROUND: The effect of immunonutrition in patients undergoing hepatectomy remains unclear. This meta-analysis aimed to assess the impact of immunonutrition on postoperative clinical outcomes in patients undergoing hepatectomy. METHODS: A literature search of PubMed, Cochrane Library, Web of Science, and Embase databases was performed to identify all randomized controlled trials (RCTs) exploring the effect of perioperative immunonutrition in patients undergoing hepatectomy until the end of March 10, 2020. Quality assessment and data extraction of RCTs were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. RESULTS: Nine RCTs involving a total of 966 patients were finally included. This meta-analysis showed that immunonutrition significantly reduced the incidences of overall postoperative complications (OR = 0.57, 95% CI: 0.34-0.95; p = 0.03), overall postoperative infectious complications (OR = 0.53, 95% CI: 0.37-0.75; p = 0.0003), and incision infection (OR = 0.50, 95% CI: 0.28-0.89; p = 0.02), and it shortened the length of hospital stay (MD = -3.80, 95% CI: -6.59 to -1.02; p = 0.007). There were no significant differences in the incidences of pulmonary infection (OR = 0.60, 95% CI: 0.32-1.12; p = 0.11), urinary tract infection (OR = 1.30, 95% CI: 0.55-3.08; p = 0.55), liver failure (OR = 0.54, 95% CI: 0.23-1.24; p = 0.15), and postoperative mortality (OR = 0.69, 95% CI: 0.26-1.83; p = 0.46). CONCLUSION: Given its positive impact on postoperative complications and the tendency to shorten the length of hospital stay, perioperative immunonutrition should be encouraged in patients undergoing hepatectomy.
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Nutrição Enteral/métodos , Ácidos Graxos Ômega-3/administração & dosagem , Hepatectomia , Assistência Perioperatória/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do TratamentoRESUMO
To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Pandemias , Pneumonia Viral , Adolescente , Adulto , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Luhong formula (LHF)-a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd-is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. METHODS: Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-ß1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-ß1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. RESULTS: LHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression. CONCLUSION: LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.
RESUMO
Five new cytochalasans, diaporthichalasins D-H (1-5), along with five known cytochalasans (6-10) were isolated from solid cultures of the endophytic fungus Diaporthe sp. SC-J0138 isolated from the leaves of Cyclosorus parasiticus. Their structures were elucidated by analysis of spectroscopic data and theoretical calculations of electronic circular dichroism spectra. Compounds 1 and 5 showed noticeable cytotoxicity against human carcinoma A549, HeLa, and HepG2 cells. The structure-activity relationships in cytotoxicity were discussed for this group of compounds.
Assuntos
Antineoplásicos/farmacologia , Ascomicetos/química , Produtos Biológicos/farmacologia , Citocalasinas/farmacologia , Células A549 , Antineoplásicos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , China , Citocalasinas/isolamento & purificação , Endófitos/química , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Folhas de Planta/microbiologia , Relação Estrutura-Atividade , Traqueófitas/microbiologiaRESUMO
INTRODUCTION: Seborrheic alopecia (SA) has clinical manifestations, duration of disease, and priorities. In the current situation where there are many and complicated clinical treatments, Western medicine treatment can delay and control the development of the disease and promote hair regeneration. However, some patients may aggravate symptoms after taking the drug, and the condition is easy to repeat after stopping the drug. Acupuncture is an important method for non-surgical treatment of SA, and it has various methods, low side effects, high safety, and simple and economical. Therefore, we will use a clinical randomized controlled study to explore the effect of acupuncture on SA, and provide a new idea and reference for the treatment of this disease. METHODS/DESIGN: We will select 60 patients diagnosed with SA. They will be randomly divided into intervention group and control groups. The control group will be given conventional treatment measures. The intervention group will receive acupuncture. Efficacy will be evaluated by comparing the skin lesion score and dermatological quality of life index before and after treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with SA. TRIAL REGISTRATION NUMBER: CTR2000030430.