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BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is commonly observed in cases of extensive hepatic resection and involves complex mechanisms. Cell senescence has been recognized as a factor in liver injury including HIRI, where it presents as a pro-inflammatory phenotype called senescence-associated secretory phenotype (SASP). Radix Rehmanniae Praeparata (RRP) is a commonly utilized traditional Chinese medicine known for its hepatoprotective, anti-aging and antioxidant qualities. Despite its recognized benefits, the specific mechanisms by which RRP may impede the progression of HIRI through the regulation of cell senescence and the identification of the most potent anti-aging extracts from RRP remain unclear. MATERIALS AND METHODS: Here, we first applied different chemical analysis methods to identify the RRP aqueous extract (RRPAE) and active fractions of RRP. Next, we constructed a surgically established mouse model and a hypoxia-reoxygenation (HR)-stimulated liver sinusoidal endothelial cells (LSECs) model to explore the underlying mechanism of RRP against HIRI through transcriptomics and multiple molecular biology experiments. RESULTS: After identifying active ingredients in RRP, we observed that RRP and its factions effectively restored LSECs fenestration and improved inflammation, cellular swelling and vascular continuity in the hepatic sinusoidal region during HIRI. Transcriptomic results revealed that RRP might reverse HIRI-induced senescence through the NOTCH signaling pathway and cell categorization further showed that the senescent cell population in HIRI liver was primarily LSECs rather than other cell types. Different RRPAE, especially RRP glucoside (RRPGLY), improved LSECs senescence and suppressed the expression of pro-inflammatory SASP genes either induced by HR insult or NOTCH1 activator, which was accompanied with the inhibition of LRP1-NOTCH1-C/EBPß pathways. Additionally, the specific inhibition of NOTCH1 by siRNA synergistically enhanced the hepatoprotective effect of RRPGLY. The ChIP-qPCR results further showed that C/EBPß was enriched at the promoter of a representative SASP, Il-1ß, in hypoxic LSECs but was significantly inhibited by RRPGLY. CONCLUSION: Our study not only clarified the potential mechanism of RRP active extractions in alleviating HIRI, but also highlighted RRPGLY was the main component of RRP that exerted anti-aging and anti-HIRI effects, providing a fresh perspective on the use of RRP to improve HIRI.
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ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a generic fibrous scarring event resulting from accumulation of extracellular matrix (ECM) proteins, easily progressing to end-stage liver diseases. Tao-Hong-Si-Wu-Tang (THSWT) is a traditional Chinese medicine formula applied in clinics to treat gynecological and chronic liver diseases. However, the role of THSWT on thioacetamide (TAA)-induced hepatic fibrosis and the specific mechanisms remains unclear. AIM OF THE STUDY: To investigate the improving effects of THSWT on TAA-insulted hepatic fibrosis and the underlying mechanisms. MATERIALS AND METHODS: UHPLC-MS/MS was performed to explore the chemical characterization of THSWT. Mice were orally administered with THSWT once daily for 6 weeks along with TAA challenge. Liver function was reflected through serum biomarkers and histopathological staining. RNA sequencing, non-targeted metabolomics and molecular biology experiments were applied to investigate the underlying mechanisms. RESULTS: THSWT profoundly repaired lipid metabolism dysfunction and blocked collagen accumulation both in TAA-stimulated mice and in hepatocytes. Results of RNA sequencing and non-targeted metabolomics revealed that the anti-fibrotic effects of THSWT mostly relied on lipid metabolism repairment by increasing levels of acetyl-CoA, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine, and decreasing relative abundances of acyl-CoA, total cholesterol, diacylglycerol, triacylglycerol and phosphatidylinositol. Mechanically, long-chain acyl-CoA synthetases 4 (ACSL4) was a key profibrotic target both in human and mice by disrupting lipid oxidation and metabolism in hepatic mitochondria. THSWT effectively blocked ACSL4 and promoted mitophagy to reverse above outcomes, which was verified by mitophagy depletion. CONCLUSION: THSWT may be a promising therapeutic option for treating hepatic fibrosis and its complications by modulating lipid metabolism and promoting mitophagy in livers.
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Medicamentos Herbarios Chinos , Metabolismo de los Lípidos , Cirrosis Hepática , Mitofagia , Tioacetamida , Animales , Mitofagia/efectos de los fármacos , Tioacetamida/toxicidad , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Masculino , Ratones Endogámicos C57BL , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Coenzima A LigasasRESUMEN
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear. METHODS: First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients. RESULTS: Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA ß-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD. CONCLUSION: In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.
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Background: In some MMD patients, the digital subtraction angiography (DSA) examination found, occlusion in the ipsilateral internal carotid artery or middle cerebral artery, accompanied by the formation of numerous moyamoya vessels. Conversely, the contralateral internal carotid artery or middle cerebral artery shows signs of stenosis without the presence of moyamoya vessels. Notably, cerebral perfusion studies reveal a similar or even more severe reduction in perfusion on the occluded side compared to the stenotic side. Importantly, clinical symptoms in these patients are typically attributed to ischemia caused by the stenotic side. This condition is referred to as unstable moyamoya disease (uMMD). Objective: This clinical research focuses on evaluating risk factors related to MMD and developing strategies to minimize postoperative complications. The study aims to analyze vascular characteristics and identify potential risk factors in patients with uMMD. Methods: The authors reviewed consecutive cases with complete clinical and radiological documentation of patients who underwent surgery between January 2018 and June 2023. Univariate analysis and multivariate logistic regression analysis were employed to understand the risk factors and prognosis of postoperative complications in uMMD. Results: Postoperative complications were retrospectively analyzed in 1481 patients (aged 14 to 65). Among them, 1,429 patients were assigned to the conventional treatment group, while 52 were in the unstable moyamoya disease group. The uMMD treatment group showed a significantly higher incidence of early postoperative complications such as RIND, cerebral infarction, and cerebral hemorrhage (p < 0.05). Univariate and multivariate logistic regression analyses were conducted on the postoperative complications of 52 uMMD patients. Initial symptoms of stenosis ≤50% (univariate: p = 0.008, multivariate: p = 0.015; OR [95% CI] =23.149 [1.853-289.217]) and choosing occluded side surgery (univariate: p = 0.043, multivariate: p = 0.018; OR [95% CI] =0.059 [0.006-0.617]) were identified as significant risk factors for postoperative neurological complications. Conclusion: Compared to the conventional treatment group, uMMD has higher complication rates, with vascular stenosis degree and surgical side selection identified as significant risk factors. A comprehensive understanding of preoperative clinical symptoms and vascular characteristics in moyamoya disease patients, coupled with the formulation of rational surgical plans, contributes positively to decreasing postoperative mortality and disability rates in uMMD.
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INTRODUCTION: Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) often coexist and increase risk for developing liver fibrosis and diabetes complications if no effective measures are taken. Dietary intervention is known to be able to achieve diabetes remission, while evidence regarding the long-term effect on liver fat is limited for comorbidity management of type 2 diabetes and NAFLD. This study aims to investigate the long-term effect of a Chinese Medical Nutrition Therapy (CMNT) diet accompanied by intermittent energy restriction on reducing liver fat and glycated haemoglobin (HbA1c) in patients with type 2 diabetes and NAFLD. METHODS AND ANALYSIS: This is a multicentre two-armed parallel randomised controlled trial study. 120 participants with type 2 diabetes and NAFLD will be recruited from the physical examination centres of multiple hospitals in China. Participants will be randomly allocated 1:1 to either the CMNT group or the usual care group. The CMNT group will be instructed to consume the provided specific meal replacement Chinese medicinal foods consisting of 6 cycles of 5 consecutive days followed by 10 days of regular food intake. The usual care group will be given standard dietary advice. Primary outcomes are changes in the controlled attenuation parameter value by transient elastography and HbA1c level. Secondary outcomes include differences in anthropometrics, clinical blood markers, questionnaires, gut microbiota and metabolomics. Further follow-up will be performed at 6 months, 1 year and 2 years. ETHICS AND DISSEMINATION: The study protocol was approved by the Biomedical Research Ethics Committee of Hunan Agricultural University (BRECHAU20200235).The results will be disseminated via relevant peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05439226.
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Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Enfermedad del Hígado Graso no Alcohólico/terapia , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/terapia , Hemoglobina Glucada/metabolismo , China , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia Nutricional/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Hígado/metabolismo , Estudios Multicéntricos como Asunto , Diagnóstico por Imagen de ElasticidadRESUMEN
Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
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Medicamentos Herbarios Chinos , MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Hígado/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Matriz Extracelular/metabolismoRESUMEN
Idiopathic pulmonary fibrosis (IPF), as the most common idiopathic interstitial pneumonia, is caused by a complex interaction of pathological mechanisms. Interestingly, IPF frequently occurs in the middle-aged and elderly populations but rarely affects young people. Salvianolic acid B (SAB) exerts antioxidant, antiinflammatory, and antifibrotic bioactivities and is considered a promising drug for pulmonary disease treatment. However, the pharmacological effects and mechanisms of SAB on cellular senescence of lung cells and IPF development remain unclear. We used bleomycin (BLM)-induced pulmonary fibrosis mice and different lung cells to investigate the antisenescence impact of SAB and explain its underlying mechanism by network pharmacology and the Human Protein Atlas database. Here, we found that SAB significantly prevented pulmonary fibrosis and cellular senescence in mice, and reversed the senescence trend and typical senescence-associated secretory phenotype (SASP) factors released from lung macrophages and alveolar type II (AT2) epithelial cells, which further reduced lung fibroblasts activation. Additionally, SAB alleviated the epithelial-mesenchymal transition process of AT2 cells induced by transforming growth factor beta. By predicting potential targets of SAB that were then confirmed by chromatin immunoprecipitation-qPCR technology, we determined that SAB directly hampered the binding of transcription factor stimulating protein 1 to the promoters of SASPs (P21 and P16), thus halting lung cell senescence. We demonstrated that SAB reduced BLM-induced AT2 and macrophage senescence, and the subsequent release of SASP factors that activated lung fibroblasts, thereby dual-relieving IPF. This study provides a new scientific foundation and perspective for pulmonary fibrosis therapy.
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Benzofuranos , Depsidos , Fibrosis Pulmonar Idiopática , Pulmón , Persona de Mediana Edad , Anciano , Humanos , Ratones , Animales , Adolescente , Pulmón/patología , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/genética , Senescencia Celular/fisiología , Macrófagos Alveolares , Bleomicina/efectos adversosRESUMEN
Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CXAE, CXAL, CXPA and CXPHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-ß (TGF-ß)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CXAE, CXAL and CXPHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CXAE and CXPHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-ß. CXPHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CXPHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CXPHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.
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BACKGROUND: Ambient air pollution was linked to elevated risks of adverse cardiovascular events, and alterations in electrophysiological properties of the heart might be potential pathways. However, there is still lacking research exploring the associations between PM1 exposure and cardiac conduction parameters. Additionally, the interactive effects of PM1 and residential greenness on cardiac conduction parameters in resource-limited areas remain unknown. METHODS: A total of 27483 individuals were enrolled from the Henan Rural Cohort study. Cardiac conduction parameters were tested by 12-lead electrocardiograms. Concentrations of PM1 were evaluated by satellite-based spatiotemporal models. Levels of residential greenness were assessed using Enhanced Vegetation Index (EVI) and Normalized difference vegetation index (NDVI). Logistic regression models and restricted cubic splines were fitted to explore the associations of PM1 and residential greenness exposure with cardiac conduction abnormalities risk, and the interaction plot method was performed to visualize their interaction effects. RESULTS: The 3-year median concentration of PM1 was 56.47 (2.55) µg/m3, the adjusted odds rate (ORs) and 95% confidence intervals (CIs) for abnormal HR, PR, QRS, and QTc interval risk in response to 1 µg/m3 increase in PM1 were 1.064 (1.044, 1.085), 1.037 (1.002, 1.074), 1.061 (1.044, 1.077) and 1.046 (1.028, 1.065), respectively. Participants exposure to higher levels of PM1 had increased risks of abnormal HR (OR = 1.221, 95%CI: 1.144, 1.303), PR (OR = 1.061, 95%CI: 0.940, 1.196), QRS (OR = 1.225, 95%CI: 1.161, 1.294) and QTc interval (OR = 1.193, 95%CI: 1.121, 1.271) compared with lower levels of PM1. Negative interactive effects of exposure to PM1 and residential greenness on abnormal HR, QRS, and QTc intervals were observed (Pfor interaction < 0.05). CONCLUSION: Long-term PM1 exposure was associated with elevated cardiac conduction abnormalities risks, and this adverse association might be mitigated by residential greenness to some extent. These findings emphasize that controlling PM1 pollution and increasing greenness levels might be effective strategies to reduce cardiovascular disease burdens in resource-limited areas.
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INTRODUCTION: The toxicity of fine particulate matter (PM2.5) is determined by its components, while the evidence regarding associations of PM2.5 components with blood pressure (BP) is limited, especially in rural areas. OBJECTIVES: This study aimed to explore the associations of PM2.5 and its chemical components with systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), mean artery pressure (MAP) levels and hypertension prevalence, and to identify key components in Chinese rural areas. METHODS: 39,211 adults from the Henan Rural Cohort were included during 2015-2017. Different periods of PM2.5 and chemical components were estimated by hybrid satellite model. The single-pollutant, component-PM2.5 model, component-residual model and component-proportion model were applied to explore the associations of pollutants with BP levels and hypertension prevalence. Exposure-response (E-R) relationships, stratified analyses and sensitivity analyses were used to explore these associations further. RESULTS: 12,826 (32.71%) were identified with hypertension. For each 1 µg/m3 increase of pollutants, the adjusted odds ratio (OR) for hypertension prevalence was 1.03 for PM2.5 mass, 1.40 for BC, 1.16 for NH4+, 1.08 for NO3-, 1.17 for OM, 1.12 for SO42- and 1.25 for SOIL in the single-pollutant model. BC and SOIL were statistically significant in the component-PM2.5 model, component-residual model and component-proportion model. Similarly, associations of these pollutants with elevated BP levels were also found in aforementioned four models. These pollutants produced a stronger association with SBP than DBP, PP and MAP. Most of associations were non-linear in E-R relationships. The groups of older, the men, with lower per capita monthly income, lower educational level and higher BMI were more vulnerable to these pollutants in stratified analyses. The results remained stable in sensitivity analyses. CONCLUSION: Long-term exposure to PM2.5 and its components, especially BC and SOIL, was associated with elevated BP and hypertension prevalence in rural adults, and decreasing pollutants may provide additional benefits.
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BACKGROUND: Previous studies indicated the beneficial influence of residential greenness on cardiovascular disease (CVD), however, the association of residential greenness with cardiac conduction performance remains unclear. This study aims to examine the epidemiological associations between residential greenness and cardiac conduction abnormalities in rural residents, simultaneously exploring the role of residential greenness for cardiac health in an explainable machine learning modeling study. METHODS: A total of 27,294 participants were derived from the Henan Rural Cohort. Two satellite-based indices, the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI), were used to estimate residential greenness. Independent and combined associations of residential greenness indices and physical activities with electrocardiogram (ECG) parameter abnormalities were evaluated using the logistic regression model and generalized linear model. The Gradient Boosting Machine (GBM) and the SHapely Additive exPlanations (SHAP) were employed in the modeling study. RESULTS: The odds ratios (OR) and 95% confidence interval (CI) for QRS interval, heart rate (HR), QTc interval, and PR interval abnormalities with per interquartile range in NDVI were 0.896 (0.873-0.920), 0.955 (0.926-0.986), 1.015 (0.984-1.047), and 0.986 (0.929-1.045), respectively. Furthermore, the participants with higher physical activities plus residential greenness (assessed by EVI) were related to a 1.049-fold (1.017-1.081) and 1.298-fold (1.245-1.354) decreased risk for abnormal QRS interval and HR. Similar results were also observed in the sensitivity analysis. The NDVI ranked fifth (SHAP mean value 0.116) in the analysis for QRS interval abnormality risk in the modeling study. CONCLUSION: A higher level of residential greenness was significantly associated with cardiac conduction abnormalities. This effect might be strengthened in residents with more physical activities. This study indicated the cruciality of environmental greenness to cardiac functions and also contributed to refining preventive medicine and greenness design strategies.
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Enfermedades Cardiovasculares , Humanos , Corazón , China/epidemiologíaRESUMEN
Objective: To analyze the safety and efficacy of regular aspirin use after combined cerebral revascularization in patients with ischemic moyamoya disease. Methods: From December 2020 to October 2021, a total of 326 patients diagnosed with ischemic moyamoya disease by global cerebral angiography and undergoing first-time combined cerebral revascularization at the Moyamoya Disease Diagnosis and Treatment Research Center of our hospital were selected. Combined cerebral revascularization: superficial temporal artery-middle cerebral artery (STA-MCA) +encephalo-duro-myo-synangiosis (EDMS).Patients were screened by 2 senior physicians according to established inclusion/exclusion criteria. Patients were divided into aspirin and non-aspirin groups based on whether they received regular oral aspirin after surgery. A total of 133 patients were enrolled in the aspirin group. A total of 71 patients (204 cases) were enrolled in the non-aspirin group. Related data were collected before and 1 year after surgery and statistically analyzed to assess the prognosis of both groups. Results: In the two groups, the mRS Score was significantly different after one year (P = 0.023). TIA occurred in 26 patients (19.5%) in the aspirin group and 27 patients (38.0%) in the non-aspirin group within one year after surgery, and the difference between the two groups was statistically significant (P = 0.004). There was no significant difference in cerebral perfusion stage, the improvement rate of cerebral perfusion, Matsushima grading, bypass patency, and other complications within one year after the operation (P > 0.05). Conclusions: In patients with ischemic moyamoya disease who underwent combined cerebral revascularization, postoperative administration of aspirin can reduce the incidence of TIA without increasing the risk of bleeding, but it can not significantly improve the cerebral perfusion of the operation side, Matsushima grading, and bypass patency.
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Moslae herba is considered to be a functional food ingredient or nutraceutical due to its rich bioactive components. The present research was carried out to investigate the effects of different temperatures (40 °C, 50 °C and 60 °C) on the drying characteristics, textural properties, bioactive compounds, flavor changes and final quality attributes of Moslae herba during the hot air-drying process. The results showed that the Midilli model could effectively simulate the drying process of Moslae herba. The effective moisture diffusivity ranged from 3.14 × 10-5 m2/s to 7.39 × 10-5 m2/s, and the activation energy was estimated to be 37.29 kJ/mol. Additionally, scanning electron microscopy (SEM) images of Moslae herba samples showed the shrinkage of the underlying epidermal layers and glandular trichomes. In total, 23 volatile compounds were detected in Moslae herba. Among them, the content of thymol increased from 28.29% in fresh samples to 56.75%, 55.86% and 55.62% in samples dried at temperatures of 40 °C, 50 °C and 60 °C, respectively, while the other two components, p-cymene and γ-terpinene, decreased with an increase in the temperature. Furthermore, both radar fingerprinting and principal component analysis (PCA) of the electronic nose (E-nose) showed that the flavor substances significantly altered during the drying process. Eventually, drying Moslae herba at 60 °C positively affected the retention of total phenolics, total flavonoids and the antioxidant capacity as compared with drying at 40 °C and 50 °C. The overall results elucidated that drying Moslae herba at the temperature of 60 °C efficiently enhanced the final quality by significantly reducing the drying time and maintaining the bioactive compounds.
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Antioxidantes , Desecación , Cinética , Desecación/métodos , Antioxidantes/farmacología , Temperatura , Fenoles/análisisRESUMEN
Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.
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Tejido Adiposo Pardo , PPAR alfa , Ratones , Animales , Tejido Adiposo Pardo/metabolismo , PPAR alfa/metabolismo , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Mitocondrias/metabolismo , Metabolismo Energético , Tejido Adiposo Blanco/metabolismo , Termogénesis , Ratones Endogámicos C57BLRESUMEN
Objectives: We aimed to explore the results of OA-PICA-protected bypass grafting in patients with severe stenosis of the vertebral artery combined with PICA. Methods: Three patients with vertebral artery stenosis involving the posterior inferior cerebellar artery, treated by the Department of Neurosurgery of Henan Provincial People's Hospital from January 2018 to December 2021, were retrospectively analyzed. All the patients underwent Occipital Artery-Posterior Inferior Cerebellar Artery (OA-PICA) bypass surgery followed by elective vertebral artery stenting. Intraoperative indocyanine green fluorescence angiography (ICGA) showed patency of the bridge-vessel anastomosis. Postoperatively, the ANSYS software was used to assess the flow pressure changes and vascular shear in combination with the reviewed DSA angiogram. CTA or DSA was reviewed 1-2 years postoperatively, and the prognosis was evaluated by the modified Rankin Scale (mRS) one year postoperatively. Results: OA-PICA bypass surgery was completed in all patients, with intraoperative ICGA showing a patent bridge anastomosis, followed by stenting of the vertebral artery, and a review of the DSA angiogram. We also employed ANSYS software evaluation of the bypass vessel, which showed stable pressure and low turnover angle, suggesting a low rate of long-term occlusion of the vessel. All patients had no procedure-related complications during their hospitalization, and were followed up for a mean of 24 months postoperatively, with a good prognosis (mRS score of 1) at 1 year postoperatively. Conclusion: OA-PICA-protected bypass grafting is an effective treatment for patients with severe stenosis of the vertebral artery combined with PICA.
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CONTEXT: The 2021 consensus report on the definition and interpretation of remission of type 2 diabetes (T2D) has been released. Although intermittent fasting diets (IF) are becoming very popular, no studies have investigated their benefit in diabetes remission. OBJECTIVE: The present study examined the effectiveness of IF in diabetes remission and potential remission durability. METHODS: Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (< 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission. RESULTS: On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32; 95% CI, 2.39-121.07; P < 0.0001). The mean body weight of participants in the CMNT group was reduced by 5.93 kg (SD 2.47) compared to 0.27 kg (1.43) in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33% (SD 0.87). The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month). CONCLUSION: This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year.
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Diabetes Mellitus Tipo 2 , Humanos , Masculino , Femenino , Hemoglobina Glucada , Glucemia , Calidad de Vida , Hipoglucemiantes/uso terapéutico , DietaRESUMEN
BACKGROUND: Evidence on the associations of fine particulate matter (PM2.5) constituents and glucose metabolism is limited in resource-limited areas. This study aimed to explore the associations of PM2.5 constituents with glucose metabolism in rural areas, and to further specify the most responsible constituent. METHODS: A total of 38,442 adults were recruited from the Henan Rural Cohort Study during 2015-2017. Three-year averaged concentrations of PM2.5 mass and its constituents (black carbon (BC), ammonium (NH4+), nitrate (NO3-), organic matter (OM), inorganic sulfate (SO42-), soil particles (SOIL) and sea salt (SS)) were estimated by a hybrid satellite-based model. Generalized linear model was applied to explore the associations of PM2.5 mass and its constituents with type 2 diabetes mellitus (T2DM), fasting blood glucose (FBG), insulin, and HOMA-ß. Proportion and residual analyses were employed to specify the most responsible constituent. RESULTS: The adjusted odds ratio (OR) for T2DM associated with 1 µg/m3 increase was 1.02 for PM2.5 mass, 1.28 for BC, 1.15 for NH4+, 1.08 for NO3-, 1.10 for OM, 1.11 for SO42-, and 1.12 for SOIL. Significant associations of PM2.5 mass and its constituents with elevated FBG, decreased insulin and HOMA-ß were also observed. Proportion and residual analyses indicated that BC was the most responsible constituent, in which 1 percentage increment in the proportion of BC in PM2.5 corresponded with 1.51-fold risk for T2DM, 0.17 mmol/L increase in FBG, 2.18 µU/mL decrease in insulin, and 38.26 % decrease in HOMA-ß; and 1 µg/m3 increment in the PM2.5-adjusted BC corresponded with 1.59-fold risk for T2DM, 0.53 mmol/L increase in FBG, 4.79 µU/mL decrease in insulin, and 91.32 % decrease in HOMA-ß. CONCLUSIONS: PM2.5 mass and its constituents (BC, NH4+, NO3-, OM, SO42-, SOIL) were associated with T2DM, increased FBG, decreased insulin and HOMA-ß, of which BC was most responsible for these associations. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375.
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Contaminantes Atmosféricos , Contaminación del Aire , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Población Rural , Pueblos del Este de Asia , Material Particulado/análisis , Hollín/análisis , Insulina , Glucosa/análisis , Contaminación del Aire/análisis , China/epidemiologíaRESUMEN
Medicine food homologous (MFH) plants and wholegrains have gained increasing attention for prevention and treatment of type 2 diabetes (T2D). Substantial evidence supports the effectiveness of intermittent energy restriction (IER) in T2D management. However, there are few studies that report intermittent use of a low-calorie pre-prepared food including MFH plants and wholegrains in T2D. The aim of this study was to investigate the effects of Chinese Medical Nutrition Therapy (CMNT), a MFH plants and wholegrains diet accompanied by IER, on glycemic control and potential mechanism. Ten-week-old diabetic db/db mice were randomly divided into CMNT group (feeding low-calorie mouse CMNT diet in day 1-4 and ad libitum regular chow for up to 7 days per cycle) and control group (ad libitum access to regular chow). The results showed that CMNT reduced fasting blood glucose, improved glucose tolerance with higher insulin secretion, attenuated macrophage infiltration, promoted ß-cell proliferation of pancreatic islets, and increased diabetes-improving microbiota (Bacteroides, Rikenellaceae_RC9_gut_group and Coprococcus_1) in db/db mice. Additionally, we performed a pilot study evaluating CMNT in thirty-nine T2D patients without obesity. Participants with T2D randomly assigned to two groups: CMNT group (receiving a consecutive 5-day low-calorie human CMNT diet with 10 days of habitual eating per cycle for 90 days) and control group (continuing on a normal diet). We observed an improvement in glycemic control in CMNT group with significant reduction in HbA1c, fasting glucose, 2 h postprandial blood glucose but control group were not affected. After CMNT intervention, the abundance of the phylum Bacteroidetes, and genus Bacteroides, Parabacteroides and Roseburia were significantly higher than baseline in T2D patient, which were closely associated with glycemic control. These findings suggested that CMNT is a promising nutritional intervention approach in diabetes management.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Islotes Pancreáticos , Animales , Glucemia , Restricción Calórica , China , Diabetes Mellitus Tipo 2/terapia , Dieta , Hemoglobina Glucada , Humanos , Ratones , Proyectos PilotoRESUMEN
Moyamoya disease is a medical condition that shows the typical characteristics like continuous and chronic thickening of the walls and the contraction of the internal carotid artery; as a result, the internal diameter of the artery gets narrowed. There are six phases of the disease ranging from I to VI (moyamoya vessels completely disappear, followed by the complete blockage of the arteries). Surgery is a commonly recommended treatment for the moyamoya disease. Our research study identifies the effect of autologous bone marrow stem cell therapy (ABMSCT) on the levels of inflammatory factors and Conexin43 (Cx43) protein in patients suffering from moyamoya. In our study, we have selected 52 moyamoya patients admitted to our hospital from 30 July 2019 to 10 February 2020. The control group (CG) was treated with superficial temporal artery to a middle cerebral artery (STA-MCA) bypass + encephalo-duro-myosinangiosis (EDMS). The experimental group (Exp. Grp) was treated with ABMSC. The cerebral vascular tissue of the patients was treated with hematoxylin-eosin (HE) staining. Immunohistochemical staining was used to identify the levels of Cx43 protein. The concentrations of vascular endothelial growth factor (VEGF), inflammatory factor interleukin-6 (IL6), interleukin-1ß (IL1ß), tumor necrosis factor (TNFα), and anti-inflammatory factor interleukin-1ß (IL1ß) were determined by enzyme-linked immunosorbent assay (ELISA). We have found that after treatment of the expression of Cx43 protein, the proportions of grade IV (7.7%), grade III (311.5%), and grade II (3.8%) patients in the Exp. Grp were lower than those in the CG. The proportion of grade I patients in the Exp. Grp (77%) was higher than that in the CG (38.5%). After treatment, the inflammatory factors IL6 (0.97 ± 0.82 pg/mL), IL1ß (8.33 ± 1.21 pg/mL), and TNFα (1.73 ± 0.71 pg/mL) in the Exp. Grp were lower than those in the CG. The anti-inflammatory factor IL1ß (15.09 ± 4.72 pg/mL) increased in the Exp. Grp compared with the CG (11.25 ± 3.48 pg/mL) post treatment. Intracranial infection, hydrocephalus, hemiplegia, and transient neurological dysfunction in the Exp. Grp were lower than those in the CG, with statistical differences (P < 0.05). Our study suggests that the treatment of autologous bone marrow stem cells (ABMSC) was beneficial to balance the inflammatory response of disorders, reduce the damage of vascular tissue in the brain, and regulate tissue repair by co-acting with various inflammatory factors as compared to traditional surgery. We conclude that the involvement of Cx43 in the occurrence and development of moyamoya. We also have found that the risk factors of intracranial infection after ABMSCT were less as compared to those after conventional surgery.
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Revascularización Cerebral , Enfermedad de Moyamoya , Médula Ósea/patología , Médula Ósea/cirugía , Células de la Médula Ósea/patología , Conexina 43 , Humanos , Interleucina-1beta , Interleucina-6 , Enfermedad de Moyamoya/patología , Enfermedad de Moyamoya/terapia , Factor de Necrosis Tumoral alfa , Factor A de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Moyamoya disease is essentially an ischemic cerebrovascular disease. Here, we describe a case of acute recurrent cerebral infarction caused by moyamoya disease with concurrent adenomyosis which, to our knowledge, is the first in the literature. A literature review is also presented. CASE SUMMARY: A 38-year-old female presented to the Research and Treatment Center of Moyamoya Disease in our hospital with "left limb weakness" as the main symptom. She was diagnosed with acute cerebral infarction and moyamoya disease through magnetic resonance imaging and digital subtraction angiography. Prior to this, she had experienced a prolonged menstrual period of one-month duration. This was investigated and adenomyosis was diagnosed. After passing the acute cerebral infarction phase, the patient underwent surgery for adenomyosis followed by combined cerebral revascularization. During the postoperative follow-up, improvements of the perfusion imaging stage and modified Rankin Scale were observed. A review of the literature showed only 16 reported cases of gynecological diseases complicated with stroke. The clinical characteristics, pathogenesis, therapeutic effects, and long-term prognosis of these cases have been studied and discussed. CONCLUSION: In patients with moyamoya disease, early management of gynecological-related bleeding disorders is essential to prevent the complications of cerebral events.