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Precipitation changes modify C, N, and P cycles, which regulate the functions and structure of terrestrial ecosystems. Although altered precipitation affects above- and belowground C:N:P stoichiometry, considerable uncertainties remain regarding plant-microbial nutrient allocation strategies under increased (IPPT) and decreased (DPPT) precipitation. We meta-analyzed 827 observations from 235 field studies to investigate the effects of IPPT and DPPT on the C:N:P stoichiometry of plants, soils, and microorganisms. DPPT reduced leaf C:N ratio, but increased the leaf and root N:P ratios reflecting stronger decrease of P compared with N mobility in soil under drought. IPPT increased microbial biomass C (+13%), N (+15%), P (26%), and the C:N ratio, whereas DPPT decreased microbial biomass N (-12%) and the N:P ratio. The C:N and N:P ratios of plant leaves were more sensitive to medium DPPT than to IPPT because drought increased plant N content, particularly in humid areas. The responses of plant and soil C:N:P stoichiometry to altered precipitation did not fit the double asymmetry model with a positive asymmetry under IPPT and a negative asymmetry under extreme DPPT. Soil microorganisms were more sensitive to IPPT than to DPPT, but they were more sensitive to extreme DPPT than extreme IPPT, consistent with the double asymmetry model. Soil microorganisms maintained stoichiometric homeostasis, whereas N:P ratios of plants follow that of the soils under altered precipitation. In conclusion, specific N allocation strategies of plants and microbial communities as well as N and P availability in soil critically mediate C:N:P stoichiometry by altered precipitation that need to be considered by prediction of ecosystem functions and C cycling under future climate change scenarios.
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Ecossistema , Solo , Solo/química , Nitrogênio/análise , Biomassa , Plantas , Microbiologia do SoloRESUMO
Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Camundongos , Animais , Isoniazida/efeitos adversos , Rifampina/efeitos adversos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Receptor 4 Toll-Like/metabolismo , Fígado , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
A clear understanding of the driving factors for different ecosystem services (ESs) is quite essential for sustainable ecosystem management. It is important to strengthen research in ESs and social sustainable development to identify the main driving factors of different ESs. This study assessed carbon sequestration (CS), water yield (WY) and soil conservation (SC) from 2000 to 2018 in the Loess Plateau using CASA (The Carnegie-AmesStanford Approach), InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) and RUSLE (Revised Universal Soil Loss Equation) models. The spatial heterogeneity, trade-offs and synergies and driving factors were explored in the whole Loess Plateau. The results showed that the WY, CS and SC had increased from 2000 to 2018. The spatial relationships between WY and SC, SC and CS, and WY and CS were mainly synergistic. Annual mean precipitation (MAP) was the dominant driving factor of WY, while normalized difference vegetation index (NDVI) and slope (SL) had the strongest explanatory power for CS and SC. The LU was the most critical factor affecting the ESs in the different climatic zones. These results could act as a reference for decision-makers on how to control various influencing factors of ESs to improve the local ecology under local conditions.
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Soil degradation is significantly increased driven by soil nutrient loss and soil erodibility, thus, hampering the sustainable development of the ecological environment and agricultural production. Vegetation restoration has been widely adopted to prevent soil degradation given its role in improving soil nutrients and soil erodibility. However, it is unclear which vegetation type has the best improving capacity from soil nutrient and soil erodibility perspectives. This study selected three vegetation restoration types of grasslands (GL), shrublands (SL), and forestlands (FL) along the five slope positions (i.e., top, upper, middle, lower, and foot slope), to investigate the effects of vegetation restoration types on soil nutrients and soil erodibility. All vegetation restoration types were restored for 20 years from croplands (CL). We used comprehensive soil nutrient index (CSNI) and comprehensive soil erodibility index (CSEI) formed by a weighted summation method to reflect the effect of vegetation restoration on the improving capacity of soil nutrient and erodibility. The results showed the vegetation types with the highest comprehensive soil quality index (CSQI) at the top, upper, middle, lower and foot slope were FL (1.92), FL (1.98), SL (2.15), FL (2.37) and GL (3.93), respectively. When only one vegetation type was considered on the entire slope, SL (0.59) and FL (0.59) had the highest CSNI, the SL had the lowest CSEI (0.34) and the highest CSQI (1.89). The CSNI was mainly influenced by soil structure stability index (SSSI), sand content, silt + clay particles, and CSEI was controlled by soil organic matter (SOM), macroaggregates and microaggregates. Moreover, the CSQI was influenced by pH, silt and clay content, and biome coverage (BC). The study suggested the SL were advised as the best vegetation restoration type on the whole slope from improving soil nutrients and soil erodibility.
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Florestas , Solo , Agricultura , China , Ecossistema , NutrientesRESUMO
Oxidative stress is widely involved in pathophysiological processes of cardiac remodeling. Molecules associated with antioxidant functions may be ideal targets for reversing cardiac remodeling. Sestrin2 is the important component of endogenous antioxidant defense, while there is little information on the pathophysiological roles of it in cardiac remodeling. The aim of this study was to investigate whether Sestrin2 is closely involved in cardiac remodeling, and whether the protective effect of pentamethylquercetin (PMQ) on cardiac remodeling is related to upregulation of the Sestrin2 endogenous antioxidant system. We generated a transverse aorta constriction (TAC)-induced pressure-overload cardiac-remodeling model in mice, and also established an isoproterenol (ISO)-induced neonatal rat cardiomyocyte (NRCM) hypertrophy model. The data showed Sestrin2 expression was downregulated significantly, and Nrf2 and HO-1 expression was also reduced in myocardial tissue or NRCM of model group, whereas keap1 expression was upregulated. PMQ significantly ameliorated cardiac remodeling and rectified the abnormal expression of Sestrin2/Nrf2/keap1. Sestrin2 small interfering RNA (SiRNA) reduced the protective effect of PMQ on NRCMs, as well as abolished its regulating effect on the Nrf2/keap1 pathway. In conclusion, Sestrin2 may be an important target in the anti-myocardial remodeling of PMQ.
Assuntos
Cardiotônicos/farmacologia , Peroxidases/metabolismo , Quercetina/análogos & derivados , Remodelação Ventricular/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Crescimento Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , RNA Interferente Pequeno/genética , Ratos , Remodelação Ventricular/fisiologiaRESUMO
Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies' response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus da Cinomose Canina , Cinomose , Vacinas Virais , Animais , Vírus da Cinomose Canina/imunologia , Cães , Camundongos , Cinomose/prevenção & controle , Cinomose/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Feminino , Imunoglobulina G/sangue , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , VacinaçãoRESUMO
Laser surface quenching (LSQ) is gaining popularity in engineering applications, but it generates non-negligible carbon emissions. However, existing research mostly focuses on quenching performance. Little attention has been paid to carbon emissions of LSQ process. In this study, we build an experimental platform including fiber laser system (IPG YLR-4 kW) and carbon emission measurement system for a synergistic study of environmental impacts and processing quality in LSQ. Based on the L16 (43) Taguchi matrix, LSQ experiments are conducted on the shield disc cutter. The influences of laser power, scanning speed, and defocusing distance on carbon emissions and hardening effects are studied. The carbon emission efficiency of LSQ is analyzed and compared with the competitive technology. The geometry and the maximum average hardness (MAH) of LSQ high-hardness zone (HHZ) are studied. A comprehensive evaluation considering carbon emissions and hardening effects is conducted. The results show that the maximum value of carbon emission is 1.4 times the minimum value. The maximum depth and width of HHZ are respectively 0.507 and 3.254 mm. The maximum MAH is 3.5 times the hardness of base metal. Compared to the average experimental responses, the experiment with the highest comprehensive score respectively increases by 26.4%, 17.1%, and 30.3% in depth, width, and MAH of HHZ, and reduces by 5.8% in carbon emissions.
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BACKGROUND: Polycystic ovary syndrome (PCOS) leads to persistent anovulation, hyperandrogenism, insulin resistance, and polycystic ovary, and is mainly characterized by menstrual disorders, and reproductive dysfunction. Angelica sinensis (Oliv.) Diels root has been used in many classical formulas of traditional Chinese medicine, and is commonly used to treat various gynecological diseases. PURPOSE: To investigate the protective effect of water extract of A. sinensis root (WEA) on PCOS rats, and the mechanism by RNA sequencing, and 16S rDNA sequencing. METHODS: The PCOS rat model was established by letrozole combined with high-fat diet (gavage; 2 months), and treated with WEA (gavage; 2 g/kg, 4 g/kg or 8 g/kg; 1 month). To evaluate the therapeutic effect of WEA on PCOS rats, vaginal smear, hematoxylin-eosin staining, and biochemical indicators detection were performed. The rat ovarian tissue was analyzed by RNA sequencing, and the results were verified by qRT-PCR, and Western blot. 16S rDNA sequencing was used to analyze the gut microbiota of rats. RESULTS: The results of the vaginal smear, and hematoxylin-eosin staining showed that WEA improved estrous cycle disorder, and ovarian tissue lesions. WEA (4 g/kg or 8 g/kg; 1 months) alleviated hormone disorders, insulin resistance, and dyslipidemia. RNA sequencing showed that WEA intervention significantly changed the expressions of 2756 genes, which were enriched in phosphatidylinositol3-kinase/phosphorylated protein kinase B (PI3K/AKT), peroxisome proliferator-activated receptor (PPAR), mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), and insulin signaling pathways. 16S rDNA sequencing found that WEA increased the species diversity of gut microbiota, and regulated the abundance of some microbiota (genus level: Dubosiella, Bifidobacterium, Coriobacteriaceae (UCG-002), and Treponema; species level: Bifidobacterium animalis, Lactobacillus murinus, and Lactobacillus johnsonii). CONCLUSION: WEA regulated hormone, and glycolipid metabolism disorders, thereby relieving the PCOS induced by letrozole combined with high-fat diet. The mechanism was related to the regulation of PI3K/AKT, PPAR, MAPK, AMPK, and insulin signaling pathways in ovarian tissues, and the maintenance of gut microbiota homeostasis. Clarifying the efficacy and mechanism of WEA in alleviating PCOS based on RNA sequencing and 16S rDNA sequencing will guide the more reasonable clinical use of WEA.
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Angelica sinensis , Resistência à Insulina , Insulinas , Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Ratos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP , Amarelo de Eosina-(YS) , Hematoxilina , Letrozol , Receptores Ativados por Proliferador de Peroxissomo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , DNA Ribossômico , Análise de Sequência de RNARESUMO
Irisin is an exercise-induced hormone that regulates lipid metabolism. The present study investigates whether the anti-obesity effect of the natural flavonoid pentamethylquercetin (PMQ) is related to irisin secretion from skeletal muscle in whole animals and cultured cells. Obese mice induced by monosodium glutamate were administered oral PMQ to determine blood irisin level and in vivo parameters of lipid metabolism, and cultured mouse C2C12 myoblasts and 3T3-L1 preadipocytes were employed to investigate the related molecular identities. PMQ increased circulating irisin and decreased bodyweight, insulin, and lipid levels accompanied with increasing brown-like adipocyte formation in obese mice. The brown adipocyte marker uncoupling protein 1 (UCP-1) and other brown-like adipocyte-specific genes and/or markers were increased in mouse white fat tissue, while PMQ treatment reversed the above changes. PMQ also dose-dependently increased the reduced levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and fibronectin type III domain-containing 5 (FNDC5) signal molecules in obese mice. Interestingly, the irisin level was increased in the culture medium of C2C12 cells treated with PMQ, and the conditioned medium stimulated the brown-like transition of 3T3-L1 preadipocytes with the increased expression of PGC-1α, FNDC5, UCP-1, and other brown-like adipocyte-specific genes. The effects of conditioned culture medium were abolished in C2C12 cells with silenced PGC-1α. On the other hand, PMQ-induced upregulation of PGC-1α and FNDC5 expression was reduced by AMPK inhibitor Compound C in C2C12 cells. Our results demonstrate the novel information that PMQ-induced irisin secretion from skeletal muscle involves the improvement of metabolic dysfunction in obese mice via activating the AMPK/PGC-1α/FNDC5 signal pathway, suggesting that PMQ modulates skeletal muscle-adipose tissue crosstalk and may be a promising drug candidate for treating obesity and obesity-related metabolic diseases.
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We numerically study turbulent Rayleigh-Bénard (RB) convection under spatial temperature modulation, where the bottom temperature varies sinusoidally around a mean value in space. Both two- and three-dimensional simulations are performed over the Rayleigh number range 10^{7}≤Ra≤10^{10} and the wave number range 1≤k≤120 at fixed Prandtl number Pr=0.7. It is demonstrated that spatial temperature modulation with small wave numbers can enhance the global heat transfer (characterized by the Nusselt number Nu) in the turbulent regime, while Nu is close to that in standard RB convection in the case of large wave numbers. Further, we propose two characteristic modulation length scales: one is the penetration depth δ_{k} above which spatial modulation is negligible, the other is the inversion depth δ_{k2} below which there exists a stable inverse temperature gradient. Based on the relative thickness of the thermal boundary layer (BL) δ_{th} compared with these two length scales, the underlying modulation mechanism is physically explained and three regimes are identified: (1) an unperturbed BL regime (δ_{k}<δ_{th}), in which the modulation effect does not penetrate through the thermal BL and Nu is nearly unchanged; (2) a partially modulated BL regime (δ_{k2}<δ_{th}<δ_{k}), in which hot spots trigger more plume emissions from the thermal BL, resulting in Nu enhancement; and (3) a fully modulated BL regime (δ_{th}<δ_{k2}), in which the stable temperature inversion over the cold phases begins to affect convective flows, which alters the trend of Nu enhancement.
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Scoparone (SCO) is known to have curative effect of alleviating liver injury. The purpose of this study was to observe the therapeutic effect and possible mechanism of SCO against high-fat diet (HFD) induced non-alcoholic liver disease (NAFLD) through in vivo experiments and RNA sequencing. Male Kunming mice were fed with HFD for 8 weeks to establish a mouse model of NAFLD, and SCO was used to treat NAFLD. Histopathology and biochemical indicators were used to evaluate the liver injury and the efficacy of SCO. RNA sequencing analysis was performed to elucidate the hepatoprotective mechanism of SCO. Finally, the differentially expressed genes of cholesterol synthesis and fatty acid (triglyceride) synthesis pathways were verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The histopathological results showed that HFD could lead to significant steatosis in mice, while SCO could alleviate liver steatosis remarkably in NAFLD mice. The determination of biochemical indicators showed that SCO could inhibit the increased serum transaminase activity and liver lipid level induced by HFD. RNA sequencing analysis of liver tissues found that 2742 and 3663 genes were significantly changed by HFD and SCO, respectively. SCO reversed the most of genes involved in cholesterol synthesis and fatty acid (triglyceride) metabolism induced by HFD. the results of the validation experiment were mostly consistent with the RNA sequencing. SCO alleviated liver injury and steatosis in NAFLD mice, which may be closely related to the regulation of cholesterol and fatty acid (triglyceride) metabolism.
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Hepatopatia Gordurosa não Alcoólica , Animais , Cumarínicos , Ácidos Graxos , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Análise de Sequência de RNA , Transaminases/uso terapêutico , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice. METHODS: We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson's staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining. RESULTS: We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation. CONCLUSION: Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway.
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Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Quercetina/análogos & derivados , Transdução de Sinais , Remodelação Ventricular/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Cardiomegalia/complicações , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Eletrocardiografia , Feminino , Fibrose , Masculino , Camundongos , Camundongos Obesos , Miocárdio/patologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Tamanho do Órgão/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Quercetina/farmacologia , Quercetina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Glutamato de SódioRESUMO
Browning white adipocytes may be a new target in anti-obesity therapy. Pentamethylquercetin (PMQ) has been shown to have anti-obesity effects in monosodium glutamate-induced obese mice. Here, we aimed to study the anti-obesity effects of PMQ in vitro and in vivo and to determine if adipose browning is involved in the mechanism underlying the anti-obesity effects of PMQ. We evaluated the effects of PMQ on cell proliferation, cell differentiation, glucose consumption, cellular lipid metabolism, and related brown gene expression in 3T3-L1 adipocytes. We also investigated the effects of PMQ in a mouse model of high-fat diet (HFD)-induced obesity. Our results demonstrated that PMQ increased the consumption of glucose, inhibited the accumulation of cellular triglycerides (TGs), and induced the expression of brown adipocyte-specific genes, such as uncoupling protein 1 (UCP-1), during the early stage of differentiation in 3T3-L1 adipocytes. In HFD mice, PMQ treatment reduced waist circumference, LEE index, white adipose tissue (WAT) weight and white adipocyte size and increased brown adipose tissue (BAT) weight. Moreover, PMQ treatment induced mitochondrial biogenesis and upregulated UCP-1 expression in WAT. These findings suggest that PMQ may induce browning of adipose tissue, a phenomenon that is at least partly related to its anti-obesity effects.
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Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Obesidade/tratamento farmacológico , Quercetina/análogos & derivados , Células 3T3-L1 , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dieta Hiperlipídica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Obesos , Quercetina/administração & dosagem , Quercetina/metabolismo , Resultado do Tratamento , Proteína Desacopladora 1/biossínteseRESUMO
Vascular dementia (VaD) is the second reason for the cognitive decline in aged people, but the effective therapy is still missing. The chronic cerebral hypoperfusion (CCH) had been widely found in VaD patients and is thought to be the key reason for cognitive impairment. Betaine is a natural product that had been implicated in many biological processes and had been used for the therapy of some neurodegenerative disease, such as Alzheimer's disease. In this study, we reported that betaine treatment could rescue the memory deficits induced by two-vessel occlusion (2-VO), a widely used CCH rat model. Betaine also restored the expression of PSD93, PSD95 and MAP2 to preserve the synaptic functions. Furthermore, betaine could reduce the oxidative stress by suppressing the MDA and ROS and enhancing the SOD and GSH. Overall, betaine treatment is able to rescue the memory deficits in CCH rats, which provide an experimental basis for the therapy of VaD.
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Betaína/uso terapêutico , Encéfalo/irrigação sanguínea , Demência Vascular/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Animais , Betaína/farmacologia , Doença Crônica , Demência Vascular/metabolismo , Demência Vascular/psicologia , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Transtornos da Memória/metabolismo , Transtornos da Memória/psicologia , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos , Sinapses/metabolismoRESUMO
Pentamethylquercetin (PMQ) has been shown to possess glucose-lowering properties, but its effect on renal fibrosis in diabetes is still unclear. This study was designed to investigate the effect of PMQ on renal fibrosis and the underlying mechanisms in spontaneous type II diabetic Goto-Kakizaki rats and mesangial cells in high glucose. We found that in Goto-Kakizaki rats, PMQ treatment attenuated glomerular volume, glycogen deposition, renal collagen and fibronectin accumulation, in addition to amelioration of diabetic symptoms, including reduction of urine volume and urine glucose levels. In mesangial cells, PMQ remarkably inhibited the cell proliferation and total collagen accumulation, and suppressed cell hypertrophy. Further experiments showed that PMQ treatment down-regulated the expression of TGF-ß1, up-regulated Smad7 and inhibited Smad2/3 activation in vivo and vitro. Our results demonstrated that PMQ ameliorated renal fibrosis in diabetes, which may be associated with suppressed TGF-ß/Smads signaling.
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Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Rim , Quercetina/análogos & derivados , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Regulação para Baixo , Fibrose , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , Quercetina/administração & dosagem , Quercetina/uso terapêutico , Ratos , Ratos Endogâmicos , Regulação para CimaRESUMO
Diabetic patients have a signifiantly higher risk of developing all forms of dementia. Pentamethylquercetin (PMQ) has been proven to have potential as an anti-diabetic agent. Nevertheless, whether PMQ can improve diabetes-induced cognitive dysfunction has not been investigated. To address this, we evaluated the effectiveness and underlying mechanisms of PMQ for ameliorating diabetes-related cognitive dysfunction in vivo and in vitro. Our results showed that Goto-Kakizaki (GK) rats displayed impairment in their learning abilities and memory capabilities. Furthermore, GK rats reflected cognitive dysfunction in proportion to the intensity of insulin resistance index. In addition, dendritic spine density and the % cell viability significantly decreased in hippocampus neurons. High glucose conditions induced hippocampal neurons damage, inflicted dendritic spine dysontogenesis, and reduced Akt/cAMP response element-binding protein activation. Treatment with PMQ in GK rats significantly ameliorated cognitive deficits and neuronal damage and increased dendritic spine density, at least in part, by improving insulin resistance and metabolic disorders. Furthermore, PMQ significantly activated the Akt/cAMP response element-binding protein pathway and increased the expression of memory-related proteins in the downstream part of the Akt/cAMP response element-binding protein pathway, such as synaptophysin and glutamate receptor 1. In addition, PMQ inhibited high glucose-induced cellular toxicity. LY294002 appeared to partly inhibit PMQ-mediated protective effects in hippocampal neurons. The results suggest that insulin resistance could predominantly reduce Akt/cAMP response element-binding protein activation in the brain, which is associated with a higher risk of cognitive dysfunction. PMQ could provide a new potential option for the prevention of cognitive dysfunction in diabetes.
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Transtornos Cognitivos/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Quercetina/uso terapêutico , Animais , Células Cultivadas , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Masculino , Quercetina/análogos & derivados , Ratos , Ratos WistarRESUMO
Pentamethylquercetin (PMQ), a methylated quercetin derivative, was screened for anti-diabetic effects in neonatally streptozotocin (STZ)-induced diabetic rats (n-STZ diabetic rats). Streptozotocin (90 mg/kg) was administered intraperitoneally to 2-day-old male pups to induce diabetes. PMQ was administered at doses of 2.5, 5, 10 and 20mg/kg/day orally when the rats were 6 weeks old and continued for 10 consecutive weeks. Body weights were followed. Fasting and fed glucose, triglyceride and insulin levels were monitored periodically at the 6th and 10th week after PMQ treatment. At the end of the study, oral glucose tolerance test was performed, and kidney and liver function parameters were assayed. It was found that PMQ intervention dose-dependently reduced postprandial glucose and triglyceride levels, prevented the onset of overt diabetes, ameliorated polydipsia symptom induced by diabetes, attenuated glucose intolerance, enhanced insulin sensitivity indices and decreased endogenous creatinine clearance rate, urinary albumin excretion rate and blood alanine aminotransferase levels of n-STZ diabetic rats in comparison to their diabetic counterparts. The results from the present study thus suggest that PMQ exhibits great potential as an antidiabetic agent by improving hyperglycemia and reducing the incidence of peripheral complications.