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BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.
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Laparoscopía , Levamisol/análogos & derivados , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Resultado del Tratamiento , Estudios de Cohortes , Neoplasias Gástricas/cirugía , Gastrectomía , Puntaje de Propensión , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugíaRESUMEN
OBJECTIVE: This study investigated the impacts of SIRT1 activation on rheumatoid arthritis (RA)-related angiogenesis. METHODS: HUVECs were cultured by different human serum. Intracellular metabolites were quantified by UPLC-MS. Next, HUVECs and rat vascular epithelial cells under different inflammatory conditions were treated by a SIRT1 agonist resveratrol (RSV). Cytokines and biochemical indicators were detected by corresponding kits. Protein and mRNA expression levels were assessed by immunoblotting and PCR methods, respectively. Angiogenesis capabilities were evaluated by migration, wound-healing and tube-formation experiments. To down-regulate certain signals, gene-specific siRNA were applied. RESULTS: Metabolomics study revealed the accelerated glycolysis in RA serum-treated HUVECs. It led to ATP accumulation, but did not affect GTP levels. RSV inhibited pro-angiogenesis cytokines production and glycolysis in both the cells, and impaired the angiogenesis potentials. These effects were mimicked by an energy metabolism interrupter bikini in lipopolysaccharide (LPS)-primed HUVECs, largely independent of HIF-1α. Both RSV and bikinin can inhibit the activation of the GTP-dependent pathway Rho/ROCK and reduce VEGF production. Abrogation of RhoA signaling reinforced HIF-1α silencing-brought changes in LPS-stimulated HUVECs, and overshadowed the anti-angiogenesis potentials of RSV. CONCLUSION: Glycolysis provides additional energy to sustain Rho/ROCK activation in RA subjects, which promotes VEGF-driven angiogenesis and can be inhibited by SIRT1 activation.
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Artritis Reumatoide , Neovascularización Patológica , Humanos , Ratas , Animales , Resveratrol/farmacología , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Lipopolisacáridos/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Citocinas/metabolismo , Glucólisis , Guanosina Trifosfato/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismoRESUMEN
OBJECTIVE: Atherosclerosis (AS) is an inflammatory disease and the formation of atherosclerotic plaque plays a critical role in AS progression. We aimed to investigate the effect of long non-coding RNA (lncRNA) activated by DNA damage (NORAD)/microRNA-495-3p (miR-495-3p)/Krüppel-like factor 5 (KLF5) axis on atherosclerotic plaque formation. METHODS: The ApoE-/- mice were fed a high-fat diet to construct AS mouse models and the modeled mice were treated with altered NORAD, miR-495-3p or KLF5. NORAD, miR-495-3p and KLF5 expression in mouse aorta tissues were evaluated, and the levels of inflammatory factors, oxidative stress factors, endothelial function indices and blood lipid in mice were all determined. The atherosclerotic plaque area, lipid deposition area, collagen fibers and CD68 expression in mouse aorta tissues were assessed. The regulatory relation between NORAD and miR-495-3p, and the target relation between miR-495-3p and KLF5 were confirmed. RESULTS: NORAD and KLF5 were increased whereas miR-495-3p was decreased in atherosclerotic mouse aortas. Inhibited NORAD or elevated miR-495-3p suppressed inflammation, oxidative stress, endothelial dysfunction, blood lipid level, atherosclerotic plaque area, collagen fibers and CD68 expression in atherosclerotic mouse aortas. Effects of elevated miR-495-3p on atherosclerotic mice could be reversed by up-regulation of KLF5. NORAD served as a sponge of miR-495-3p and miR-495-3p directly targeted KLF5. CONCLUSION: Silenced NORAD elevated miR-495-3p to suppress atherosclerotic plaque formation via reducing KLF5. Findings in our research may be helpful for exploring molecular mechanisms of AS.
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Apolipoproteínas E/genética , Aterosclerosis/genética , Factores de Transcripción de Tipo Kruppel/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Animales , Aterosclerosis/patología , Daño del ADN/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/genética , Humanos , Inflamación/genética , Inflamación/patología , Ratones , Ratones Noqueados , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologíaRESUMEN
Oxadiazole is a five-membered heterocyclic compound containing two nitrogen atoms and one oxygen atom. The 1,3,4-oxadiazole and 1,2,4-oxadiazole have favourable physical, chemical, and pharmacokinetic properties, which significantly increase their pharmacological activity via hydrogen bond interactions with biomacromolecules. In recent years, oxadiazole has been demonstrated to be the biologically active unit in a number of compounds. Oxadiazole derivatives exhibit antibacterial, anti-inflammatory, anti-tuberculous, anti-fungal, anti-diabetic and anticancer activities. In this paper, we report a series of compounds containing oxadiazole rings that have been published in the last three years only (2020-2022) as there was no report or their activities described in any article in 2019, which will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.
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Química Farmacéutica , Oxadiazoles , Antibacterianos/farmacología , Técnicas de Química Sintética , Oxadiazoles/química , Oxadiazoles/farmacologíaRESUMEN
Maggot extracts promote wound healing, but their bioactive part(s) and molecular effects on the regenerating tissues/cells remain largely unclear. These issues are addressed here by treating rat skin wounds, human keratinocyte line/HaCat and fibroblasts with maggot secretion/excretion, and the extracts of maggots without and with secretion/excretion. The wound closure rates, cell proliferation activities, and statuses of wound healing-related signaling pathways (STAT3, Notch1, Wnt2, NF-κB, and TGF-beta/Smad3) and their downstream gene expression (c-Myc, cyclin D1, and VEGF) are evaluated by multiple approaches. The results reveal that the maggot extracts, especially the one from the maggots without secretion/excretion, show the best wound healing-promoting effects in terms of quicker wound closure rates and more rapid growth of keratinocytes and fibroblasts. Of the five signaling pathways checked, the ones mediated by TGF-beta/Smad3, and STAT3 are activated in the untreated wounds and become further enhanced by the maggot extracts, accompanied with c-Myc, VEGF, and cyclin D1 up-regulation. Our results thus show (1) that both body extract and secretion/excretion of maggots contain favorable wound healing elements and (2) that the enhancement of TGF-beta/Smad3 and STAT3 signaling activities may be the main molecular effects of maggot extracts on the wound tissues.
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Proliferación Celular/fisiología , Fibroblastos/metabolismo , Proteínas de Insectos/aislamiento & purificación , Piel/patología , Cicatrización de Heridas/fisiología , Heridas y Lesiones/patología , Animales , Células Cultivadas , Dípteros/citología , Humanos , Larva , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Piel/lesionesRESUMEN
We aimed to describe the human resources and apparatuses of community health service (CHS) in Tongliao City of China and investigate the differences between CHS centers and stations. Field investigations and questionnaire-based surveys were conducted in 120 CHS organizations of Tongliao City, which were selected by a stratified multistage random cluster sampling method. Data were collected on the human resources, medical apparatuses, and satisfaction of covered residents. We found that the total number, educational background, and professional titles of staff were lower at stations than at centers. Although the categories of providing health services were comparable between centers and stations, stations provided fewer health services than centers did. In addition, stations owned fewer apparatuses compared with centers. The percentages of satisfaction on many items were lower among residents covered by stations than among those covered by centers. Desired health services provided by CHS organizations have been partially accomplished in Tongliao City. Attracting more highly educated professionals and purchasing more valuable apparatuses may be helpful to improve the unbalanced distribution in human resources and apparatuses between centers and stations. Appropriate modifications of corresponding policies should be taken into consideration by the local government in the future.
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Centros Comunitarios de Salud/estadística & datos numéricos , Servicios de Salud Comunitaria/estadística & datos numéricos , Equidad en Salud , Personal de Salud/estadística & datos numéricos , Satisfacción del Paciente , Calidad de la Atención de Salud , China , Necesidades y Demandas de Servicios de Salud , Humanos , Gobierno Local , Encuestas y CuestionariosRESUMEN
Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.
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Quimiocinas , Depresión , Ratas Sprague-Dawley , Animales , Masculino , Depresión/tratamiento farmacológico , Quimiocinas/metabolismo , Ratas , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento Molecular , Conducta Animal/efectos de los fármacos , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Hipocampo/metabolismo , Hipocampo/efectos de los fármacosRESUMEN
SCOPE: This study investigates the impacts of lard and related fatty acids intake on rheumatoid arthritis (RA) animal models. METHOD AND RESULTS: Collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) are induced in SD rats and C57 BL/6 mice respectively, which are fed by lard-rich diet (LRD) for 42 days with intake restriction or not. AIA SD rats are treated by representative fatty acids for 30 days. Body weight, arthritis score, and metabolic profile are periodically recorded. Monocyte distribution, cytokine/metabolites levels, gene expression, and tissue damages are investigated by flow cytometry, ELISA, colorimetry, PCR, and histological methods. After being treated by fatty acids in vitro, THP-1 monocytes and the corresponding medium are collected for ELISA, PCR, immunoblotting, and reporter gene assays. Irrespective of intake amounts, LRD decreases inflammatory cytokines and inhibits glycolysis in all rheumatic rodents. Furthermore, it alters monocyte distribution and promotes PPAR-γ expression in AIA mice. Overall evidences show that both saturated (SF) and unsaturated fatty acids (USF) from lard can attenuate inflammation by activating PPAR-γ. Silencing PPAR-γ abrogates their anti-inflammatory effects in vitro. Besides, SF can stimulate TLR4/NF-κB pathway. CONCLUSION: Lard consumption is beneficial for active inflammatory arthritis recovery. Even SF can activate PPAR-γ and consequently attenuate inflammation.
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Artritis Experimental , PPAR gamma , Ratas , Ratones , Animales , PPAR gamma/genética , PPAR gamma/metabolismo , Ácidos Grasos , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Ratas Sprague-Dawley , Citocinas/metabolismo , FN-kappa B/metabolismo , InflamaciónRESUMEN
Formononetin as a Bax agonist exhibits anticancer effects. To identify novel Bax agonist, 18 new structurally modified formononetin derivatives were synthesised and their anticancer activities were evaluated in the A549 and Beas-2b cell lines. The results indicated that 7a elicited the most potent inhibitory effect against the A549 cell line, with an IC50 value of 0.87 µM, and no obvious toxicity to Beas-2b cells. These results indicated that 7a was 40-fold and 6.94-fold more efficacious than Formononetin and Doxorubicin, respectively. Additionally, western blot and immunofluorescence assays demonstrated that 7a downregulated the protein expression of Bcl-2 and upregulated the expressions of Bax to promote A549 apoptosis, the obtained results also suggested that 7a had the potential to be developed into a lead compound that can be applied in the prevention and treatment of lung cancer.
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BACKGROUND: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. OBJECTIVE: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. METHOD: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), PM with aerodynamic diameter ≤10µm (PM10), sulfur dioxide (SO2), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. RESULTS: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of PM2.5, PM10, SO2 and CO were the 21th to 24th weeks of pregnancy. Every 10-µg/m3 increase in PM2.5 and PM10, 5-µg/m3 increase in SO2, and 0.1-mg/m3 increase in CO was associated with low maternal hemoglobin levels [-0.94g/L (95% confidence interval (CI): -1.15, -0.73), -1.31g/L (95% CI: -1.55, -1.07), -2.96g/L (95% CI: -3.32, -2.61), and -1.11g/L (95% CI: -1.31, -0.92), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. CONCLUSIONS: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.
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Contaminantes Atmosféricos , Contaminación del Aire , Efectos Tardíos de la Exposición Prenatal , Recién Nacido , Embarazo , Humanos , Femenino , Hierro/análisis , Estudios Prospectivos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , China , Hemoglobinas/análisis , Suplementos Dietéticos/análisis , Exposición MaternaRESUMEN
Background: Embryonic neural development is associated with intrauterine nutritional status. However, few cohort studies estimated the relationship between maternal dietary patterns during pregnancy and offspring's early neurodevelopment. Objective: To examine the impact of the Mediterranean diet (MD) during pregnancy on infant neurodevelopment, including the potential mediating role of cord blood metabolites. Methods: Among 1,471 mother-child pairs in a prospective birth cohort study in Hefei, China, we investigated the associations between maternal MD score [calculated based on a validated food frequency questionnaire (FFQ)] and child neurodevelopment at infancy [assessed using Ages and Stages Questionnaires, Third Edition (ASQ-3)]. The cord blood metabolic markers (including C-peptide, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) were measured. Results: The MD score was negatively associated with communication domain developmental delays in infants [relative risk (RR) with 95% CI: 0.34 (0.16, 0.72)]. Compared with girls, boys born from mothers with lower MD scores during pregnancy were inclined to the failure of the communication domain [RRs with 95% CI for boys: 0.34 (0.14, 0.84); for girls: 0.26 (0.06, 1.18)]. Mediation analysis showed that the association between the maternal MD score and failure of communication domain mediated by C-peptide was 19.4% in boys but not in girls. Conclusion: Adhering to the MD during pregnancy was associated with a decreased risk of poor neurodevelopment, possibly mediated by lower levels of cord blood C-peptide.
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Background: The relationship between vitamin D status and gestational cardiovascular health (CVH) is inconsistent in previous studies. Emerging evidence shows that sleep behaviors are related to vitamin D metabolism. However, no studies evaluate the interaction of vitamin D and sleep behaviors on gestational CVH. Objective: We aimed to estimate the relationship between 25-hydroxyvitamin D [25(OH)D] concentrations and gestational CVH, and whether the relationship was modified by sleep behaviors. Methods: The data of this study was from a multicenter birth cohort study. A total of 9,209 pregnant women at 16-23 weeks of gestation were included. 25(OH)D concentrations were measured from collected blood. Sleep patterns consisted of major sleep behaviors including duration, chronotype, insomnia, snoring, and excessive daytime sleepiness. Data on poor CVH was based on four "clinical" CVH metrics, including body mass index, blood pressure, total cholesterol, and glucose levels. Results: The proportion of women with poor CVH was 25.0%. The relative risk (RR) (95%CI) of poor CVH was 0.67 (0.58-0.76) in women with 25(OH)D ≥ 50 nmol/L after multivariate adjustments. Lower 25(OH)D concentrations were significantly associated with poor CVH. Such association was also evident in subgroups analysis. We found a significant interaction of 25(OH)D (P for interaction = 0.01) with sleep patterns on the risk of poor CVH. A negative dose-response relation was observed between 25(OH)D concentrations and poor CVH risk in healthy or intermediate sleep, not poor sleep. 25(OH)D concentrations were lower and the risk of poor CVH was higher in pregnant women with poor sleep patterns (P < 0.05). Conclusion: Our study suggests that sleep patterns modify the association of 25(OH)D concentrations with the CVH among pregnant women.
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Background: Pro-inflammatory diets play an important role in developing cardiovascular disease (CVD). Vitamin D has been demonstrated to have an anti-inflammatory effect and promote cardiovascular health (CVH). However, it is unclear whether adequate vitamin D during pregnancy protects against poor CVH caused by pro-inflammatory diets. Objective: To investigate the association of pro-inflammatory diets with the cardiovascular risk (CVR) among pregnant women and whether such association was modified by vitamin D status. Methods: The study was based on a prospective birth cohort that included 3,713 pregnant women between 16 and 23 gestational weeks. In total, 25(OH)D concentrations and high-sensitivity C-reactive protein (hs-CRP) were measured from the collected blood. The dietary inflammatory potential was evaluated using the empirical dietary inflammatory pattern (EDIP) score based on a validated food frequency questionnaire. Gestational CVR was evaluated using the CVR score based on five "clinical" CVR metrics, including body mass index, blood pressure, total cholesterol, glucose levels, and smoking status. Results: The proportion of women with a CVR score >0 was 54.3%. We observed a positive association between the EDIP score and CVR score. Compared with the lowest quartile, the CVR score (ß = -0.114, 95% CI, -0.217, -0.011) and hs-CRP levels (ß = -0.280, 95% CI, -0.495, -0.065) were lower in the highest quartile (P for trend <0.05). Increased CVR connected with high EDIP score was observed only in women with 25(OH)D concentrations <50 nmol/L (RR = 1.85; 95% CI: 1.35, 2.54). Mediation analysis revealed that the proportion of association between the EDIP score and CVR score mediated by 25(OH)D was 28.7%, and the proportion of the association between 25(OH)D and the CVR score mediated by hs-CRP was 21.9%. Conclusion: The higher dietary inflammatory potential was associated with an increased CVR during pregnancy by promoting inflammation. Adequate vitamin D could exert anti-inflammatory effects and modify such association.
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ETHNOPHARMACOLOGICAL RELEVANCE: Sugemule-3 decoction (SD-3) is a commonly used prescription in Mongolian medicine which composed of the herbs Baidoukou (the fruit of Amomum compactum Sol. ex Maton), Baijusheng (the fruit of Lactuca sativa L.) and Biba (Piper longum L.). SD-3 has remarkable effect on the cardiovascular diseases, but its pharmacological mechanism has not been elucidated. AIM OF THIS STUDY: To evaluate the cardioprotective effects and the potential mechanisms of the ethanol extracts of SD-3 against isoproterenol (ISO)-induced heart failure (HF) in rats. MATERIAL AND METHODS: The ethanol extracts of SD-3 were prepared and analyzed by LC-ESI-MS/MS. One hundred male Wistar rats were randomly divided into five groups: control, ISO (HF) and different doses of SD-3 (0.4, 0.2, 0.1 g/kg/d) groups. HF model rats were established by intraperitoneal injecting of ISO. The left ventricular function was evaluated by echocardiography. Myocardial injury and fibrosis were examined by hematoxylin-eosin (HE) and Masson staining. Western-blot analysis was performed to determine the protein expression of apoptosis and mitochondrial dynamics in all the groups. Moreover, the structural changes in the mitochondria of cardiomyocytes were also observed by transmission electron microscopy. RESULTS: Fifteen compounds were detected in the ethanol extracts of SD-3, include piperine, piperanine, etc. Rats administered with ISO showed a significant decline in the left ventricular function. The cardiac histopathological changes such as local necrosis, interstitial edema, and cardiac fibrosis were also observed in the ISO group. The treatment with SD-3 significantly inhibited these effects of ISO. ISO was found to increase the protein expression of Bax, cleaved-PARP and cleaved-caspase-3, -7 -9, destroy the balance between mitochondrial fusion and fission, and alter the mitochondrial morphology. The ethanol extracts of SD-3 could rebalance mitochondrial fusion and fission, and ameliorates the morphological abnormalities induced by ISO in mitochondria. CONCLUSION: The current study demonstrated that ethanol extracts of SD-3 improved isoprenaline-induced cardiac hypertrophy and fibrosis through inhibiting cardiomyocyte apoptosis and regulating the mitochondrial dynamics.
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Insuficiencia Cardíaca , Dinámicas Mitocondriales , Animales , Etanol/química , Fibrosis , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/prevención & control , Isoproterenol/toxicidad , Masculino , Miocardio/patología , Ratas , Ratas Wistar , Espectrometría de Masas en TándemRESUMEN
Understanding the microbial and chemical diversities, as well as what affects these diversities, is important for modern manufacturing of traditional fermented foods. In this work, Chinese dark teas (CDTs) that are traditional microbial fermented beverages with relatively high sample diversity were collected. Microbial DNA amplicon sequencing and mass spectrometry-based untargeted metabolomics show that the CDT microbial ß diversity, as well as the nonvolatile chemical α and ß diversities, is determined by the primary impact factors of geography and manufacturing procedures, in particular, latitude and pile fermentation after blending. A large number of metabolites sharing between CDTs and fungi were discovered by Feature-based Molecular Networking (FBMN) on the Global Natural Products Social Molecular Networking (GNPS) web platform. These molecules, such as prenylated cyclic dipeptides and B-vitamins, are functionally important for nutrition, biofunctions, and flavor. Molecular networking has revealed patterns in metabolite profiles on a chemical family level in addition to individual structures.
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Camellia sinensis , Alimentos Fermentados , China , Fermentación , Metabolómica/métodosRESUMEN
The regulatory function of global regulator NtrC on curdlan biosynthesis and nitrogen consumption under nitrogen-limited condition in Agrobacterium sp. ATCC 31749 was investigated. The ntrC mutant of Agrobacterium sp. was constructed by homologous recombination. The ability to utilize NH4Cl and KNO3 was impaired in the mutant. Other nitrogenous compounds, such as glutamic acid and glutamine, were utilized normally. Curdlan production capability was impaired severely in the mutant. Curdlan production was 5-fold lower than the wild type strain in batch fermentation with NH4Cl as the sole nitrogen source. However, up to 6.5 g l(-1) of a newly found alkali-insoluble biopolymer was produced by the ntrC mutant when glutamic acid was used as nitrogen source. The new biopolymer had glycosidic bond and hydroxyl group but no ß-configuration absorption peak on IR spectrum was found as different from curdlan. In addition, the mutant exhibited a rapid morphological change from the dot to rod form. These results deduced that the global regulator NtrC was involved in curdlan and other biopolymer biosynthesis in Agrobacterium sp. ATCC 31749 in response to nitrogen-limited condition.
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Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Mutación , Compuestos de Nitrógeno/metabolismo , Rhizobium/metabolismo , beta-Glucanos/metabolismo , Nitrógeno/metabolismo , Rhizobium/genéticaRESUMEN
To investigate the association between the single nucleotide polymorphisms (SNPs) in adiponectin gene promoter and essential hypertension (EH) in Chinese Korean and Han of Yanbian area, 220 EH patients and 268 normotensive control individuals were enrolled. PCR and direct DNA sequencing were used to determine the -11426A>G (rs16861194), -11391G>A (rs17300539), -11377C>G (rs62620185), -11156insCA (rs60806105), and -11043C>T (rs76786086) SNPs in the promoter region of adiponectin gene. Total cholesterol (TC), the triglyceride (TG), fasting plasma glucose (FPG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) levels were examined by oxi-dase method. The plasma adiponectin and insulin were measured by enzyme linked immunosorbent assay (ELISA). The results showed that: (1) SNPs of -11426A>G, -11377C>G, and -11156insCA were found and in Hardy-Weinberg equilib-rium (P>0.05), but not the case in -11391G>A and -11043C>T. (2) -11426A>G and -11156insCA were perfectly in link-age disequilibrium (D'=1; r2=1). (3) The allele G frequency of -11426A>G polymorphism in Chinese Korean (21.10%) was significantly higher than that in Chinese Han (12.50%), and also higher in EH group than in the control group of Chinese Han. The genotype and allele frequencies of -11377C>G showed no significant difference between the two groups ob-served. (4) The haplotype -11426G -11377C frequency in EH of Chinese Han was higher than in the control group (P<0.05). (5) The EH showed lower plasma adiponectin level compared with the control group (P<0.001) in both Chinese Korean and Han. Our results indicate that: (1) the perfect linkage disequilibrium of -11426A>G and -11156insCA is first reported, and the SNP of -11426A>G is associated with Chinese Han and Korean. (2) -11426 G and -11426G -11377C are risk factor and risk haplotype in Yanbian Chinese Han, but not in Chinese-Korean. (3) The lower hypoadiponectinemia is the important risk factors for EH in Chinese Korean and Han of Yanbian area. (4) There is no relationship between -11426A>G polymorphism and the plasma adiponectin level.
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Adiponectina/genética , Hipertensión/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Adiponectina/sangre , Adulto , Anciano , China/etnología , Frecuencia de los Genes , Genotipo , Humanos , Corea (Geográfico)/etnología , Desequilibrio de Ligamiento , Persona de Mediana EdadRESUMEN
Cigarette smoke- (CS-) induced oxidative stress and inflammation in the lung are serious health problems. Primary and reprocessed tea products contain multiple antioxidants that have been reported to protect the lung against CS-induced injury. However, the beneficial effects of Eurotium cristatum fermented loose dark tea (ECT) and Eurotium cristatum particle metabolites (ECP) on CS-induced lung injury and its potential hepatic metabolic detoxification are still unclear. Therefore, sixty mice were randomly divided into six equal groups. CS-exposed mice were prevented or treated with ECP or ECT infusions for 12 or 8 weeks to determine the antioxidative stress, anti-inflammatory and potential metabolic detoxification of ECT and ECP. Thirty-six mice were randomly divided into six equal groups to observe the effects on hepatic metabolic detoxification by replacing daily drinking water with ECT. Results showed that CS significantly decreased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and upregulated the expressions of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1ß in serum. These adverse effects were modulated by ECP and ECT. In addition, ECT upregulated the mRNA expression of pregnane X receptor (PXR) and cytochrome P450 (CYP450) in the liver on daily free drinking ECT mice group. Western blot analysis further revealed that in CS-exposed mice, ECP and ECT significantly decreased the phosphorylation of mitogen-activated protein kinase (MAPK) in the lung but upregulated the protein expressions of PXR and aryl hydrocarbon receptor (AhR) in the liver. Overall, our findings demonstrated that ECT and ECP protected against lung injury induced by CS via MAPK pathway and enhanced hepatic metabolic detoxification via PXR and AhR pathways. Therefore, daily intake of ECT and ECP can potentially protect against CS-induced oxidative and inflammatory injuries.
Asunto(s)
Aspergillus/clasificación , Fumar Cigarrillos/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Pulmón/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fase I de la Desintoxicación Metabólica , Extractos Vegetales/farmacología , Receptor X de Pregnano/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Fumar Cigarrillos/patología , Femenino , Pulmón/patología , Lesión Pulmonar/metabolismo , Ratones , Extractos Vegetales/químicaRESUMEN
BACKGROUND: Depression can seriously affect the quality of life of type 2 diabetes mellitus (T2DM) patients after stroke. However, there were still no objective methods to diagnose T2DM patients with poststroke depression (PSD). Therefore, we conducted this study to deal with this problem. METHODS: Gas chromatography-mass spectroscopy (GC-MS)-based metabolomics profiling method was used to profile the urinary metabolites from 83 nondepressed T2DM patients after stroke and 101 T2DM patients with PSD. The orthogonal partial least-squares discriminant analysis was conducted to explore the metabolic differences in T2DM patients with PSD. The logistic regression analysis was performed to identify the optimal and simplified biomarker panel for diagnosing T2DM patients with PSD. The receiver operating characteristic curve analysis was used to assess the diagnostic performance of this biomarker panel. RESULTS: In total, 23 differential metabolites (7 decreased and 16 increased in T2DM patients with PSD) were found. A panel consisting of pseudouridine, malic acid, hypoxanthine, 3,4-dihydroxybutyric acid, fructose and inositol was identified. This panel could effectively separate T2DM patients with PSD from nondepressed T2DM patients after stroke. The area under the curve was 0.965 in the training set and 0.909 in the validation set. Meanwhile, we found that the galactose metabolism was significantly affected in T2DM patients with PSD. CONCLUSION: Our results could be helpful for future development of an objective method to diagnose T2DM patients with PSD and provide novel ideas to study the pathogenesis of depression.