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1.
Virol J ; 21(1): 116, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783310

RESUMO

OBJECTIVE: Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics. METHODS: In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract. RESULTS: Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families. CONCLUSION: The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies.


Assuntos
Doenças do Cão , Equinococose , Echinococcus , Fezes , Microbioma Gastrointestinal , Animais , Cães , Equinococose/veterinária , Doenças do Cão/parasitologia , Doenças do Cão/microbiologia , Doenças do Cão/virologia , China , Fezes/parasitologia , Fezes/microbiologia , Fezes/virologia , Echinococcus/genética , Echinococcus/isolamento & purificação , Genoma Viral , Vírus/classificação , Vírus/isolamento & purificação , Vírus/genética
2.
J Sci Food Agric ; 104(7): 4331-4341, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38299439

RESUMO

BACKGROUND: Human milk fat analog emulsion (HMFAE) is an emulsion that mimics the composition and structure of human milk (HM) fat globules. The application of HMFAE in infant formula requires a series of milk powder processing steps, such as pasteurization and spray drying. However, the effect of milk powder processing on fat digestion of HMFAE is still unclear. In this study, the influence of pasteurization and spray drying on the lipolysis behavior of HMFAE was studied and compared with HM using a simulated infant in vitro digestion model. RESULTS: Pasteurization and spray drying increased the flocculation and aggregation of lipid droplets in HMFAE during digestion. Spray drying destroyed the lipid droplet structure of HMFAE, and partial milk fat globule membrane-covered lipid droplets turned into protein-covered lipid droplets, which aggravated lipid-protein aggregation during gastric digestion and hindered fat digestion in the small intestine. The final lipolysis degree was in the order HM (64.55%) > HMFAE (63.41%) > pasteurized HMFAE (61.75%) > spray-dried HMFAE (60.57%). After complete gastrointestinal digestion, there were no significant differences in free fatty acid and sn-2 monoacylglycerol profile among the HMFAE, pasteurized HMFAE, and spray-dried HMFAE. CONCLUSION: Milk powder processing can reduce lipolysis by altering the lipid droplet structure of HMFAE and the degree of lipid droplet aggregation during digestion. © 2024 Society of Chemical Industry.


Assuntos
Leite Humano , Pasteurização , Lactente , Humanos , Leite Humano/química , Emulsões/análise , Secagem por Atomização , Pós/análise , Digestão
3.
J Cardiovasc Pharmacol ; 80(5): 718-724, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35881908

RESUMO

ABSTRACT: There is no clear consensus on the safety of renin-angiotensin-aldosterone system inhibitors in patients with contrast media exposure. We aimed to assess the safety of renin-angiotensin-aldosterone system inhibitors in patients exposed to contrast media at 1-year follow-up. Patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) were recruited and randomly divided into 2 groups (1:1 ratio): with ACEI/ARB group (ACEI/ARB continued throughout the study period) and without ACEI/ARB group (ACEI/ARB stopped 24 hours before and continued 48 hours after the procedure). The primary endpoint was contrast-induced acute kidney injury (CI-AKI) and secondary endpoints were major adverse cardiovascular events (MACEs), and the need for renal replacement therapy during hospitalization and at 1-year follow-up. The occurrence rates of CI-AKI were not comparable in the ACEI/ARB group and the without ACEI/ARB group (2.92% and 2.62%, respectively; P = 0.866). No significant between-group differences were found with respect to the frequency of MACEs or renal replacement therapy during hospitalization and at 1-year follow-up. On subgroup analysis, among patients with estimated glomerular filtration rate (eGFR) < 45 mL/min, the incidence of CI-AKI was significantly higher in the ACEI/ARB group [17.95% (14/78) vs. 6.02% (5/83), P = 0.029]. Among patients with eGFR ≥ 45 mL/min, the incidence of CI-AKI was comparable in the 2 groups [0.87% (5/572) vs. 2.12% (12/567), P = 0.094]. The incidence of MACEs and renal replacement therapy was not comparable in the 2 groups, during hospitalization and at 1-year follow-up. ACEI or ARB treatment can safely be continued after exposure to contrast media, but not in patients with eGFR < 45 mL/min.


Assuntos
Injúria Renal Aguda , Inibidores da Enzima Conversora de Angiotensina , Humanos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Sistema Renina-Angiotensina , Meios de Contraste/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia
4.
Biol Chem ; 402(7): 795-803, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33544461

RESUMO

Multiple studies have showed that berberine protects against heart diseases, including obesity-associated cardiomyopathy. However, it is not fully disclosed the potential molecular mechanisms of berberine on controlling cardiac remodeling. Kruppel-like factor (KLF) 4, identified as a critical transcriptional factor, participates in multiple cardiac injuries. The present study was to explore whether KLF4 determined the cardioprotective benefits of berberine in dietary-induced obese mice. High fat diet-induced obese mice were treated with berberine with or without lentivirus encoding Klf4 siRNA, and cardiac parameters were analyzed by multiple biological approaches. In dietary-induced obese mouse model, administration of berberine obviously increased cardiac level of KLF4, which closely correlated with improvement of cardiac functional parameters. Co-treatment of lentivirus encoding Klf4 siRNA abolished cardioprotective benefits of berberine, including induction of cardiac hypertrophy, fibrosis, functional disorders, inflammatory response and oxidative stress. Mechanistically, we found berberine improved cardiac mitochondrial biogenesis and activities, whereas silencing Klf4 decreased berberine-upregulated mitochondrial quality, ATP production and oxygen consumption. Our present study demonstrated that berberine protected against dietary-induced cardiac structural disorders and mitochondrial dysfunction dependent on cardiac KLF4 signaling. Cardiac KLF4 was one of potential therapeutic targets for obesity-induced cardiac injuries.


Assuntos
Berberina/farmacologia , Fatores de Transcrição Kruppel-Like/metabolismo , Mitocôndrias/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Suplementos Nutricionais/efeitos adversos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo
5.
J Cell Mol Med ; 24(9): 5205-5212, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32220004

RESUMO

Atherosclerosis is one of leading phenotypes of cardiovascular diseases, featured with increased vascular intima-media thickness (IMT) and unstable plaques. The interaction between gastrointestinal system and cardiovascular homeostasis is emerging as a hot topic. Therefore, the present study aimed to explore the role of an intestinal protein, intestinal fatty acid-binding protein (I-FABP/FABP2) in the atherosclerotic progress. In western diet-fed ApoE-/- mice, FABP2 was highly expressed in intestine. Silence of intestinal Fabp2 attenuated western diet-induced atherosclerotic phenotypes, including decreasing toxic lipid accumulation, vascular fibrosis and inflammatory response. Mechanistically, intestinal Fabp2 knockdown improved intestinal permeability through increasing the expression of tight junction proteins. Meanwhile, intestinal Fabp2 knockdown mice exhibited down-regulation of intestinal inflammation in western diet-fed ApoE-/- mice. In clinical patients, the circulating level of FABP2 was obviously increased in patients with cardiovascular disease and positively correlated with the value of carotid intima-media thickness, total cholesterol and triglyceride. In conclusion, FABP2-induced intestinal permeability could address a potential role of gastrointestinal system in the development of atherosclerosis, and targeting on intestinal FABP2 might provide a therapeutic approach to protect against atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Aterosclerose/patologia , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/metabolismo , Inflamação/patologia , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/complicações , Colesterol , Dieta Hiperlipídica , Proteínas de Ligação a Ácido Graxo/sangue , Técnicas de Silenciamento de Genes , Inflamação/complicações , Masculino , Camundongos Knockout , Permeabilidade
6.
J Cell Mol Med ; 24(23): 13727-13738, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33108705

RESUMO

Vascular complications from diabetes often result in poor outcomes for patients, even after optimized interventions. Forkhead box protein O1 (FoxO1) is a key regulator of cellular metabolism and plays an important role in vessel formation and maturation. Alterations of FoxO1 occur in the cardiovascular system in diabetes, yet the role of FoxO1 in diabetic vascular complications is poorly understood. In Streptozotocin (STZ)-induced type 1 diabetic rats, FoxO1 expression was up-regulated in carotid arteries at 8 weeks of diabetes that was accompanied with adverse vascular remodelling characterized as increased wall thickness, carotid medial cross-sectional area, media-to-lumen ratio and decreased carotid artery lumen area. This adverse vascular remodelling induced by hyperglycaemia in diabetic rats required FoxO1 activation as pharmacological inhibition of FoxO1 with 50mg/kg AS1842856 (AS) reversed vascular remodelling in type 1 diabetic rats. The adverse vascular remodelling in type 1 diabetes mellitus (T1DM) occurred concomitantly with increases in pro-inflammatory factors, adhesion factors, apoptosis, NOD-like receptor family protein-3 inflammasome activation and the phenotypic switch of arterial smooth muscle cells, which were all reversed by AS. In addition, FoxO1 inhibition counteracted the down-regulation of its upstream mediator PDK1 in T1DM. PDK1 activator reduced FoxO1 nuclear translocation, which serves as the basis for subsequent transcriptional regulation during hyperglycaemia. Taken together, our data suggest that FoxO1 is a critical trigger for type 1 diabetes-induced vascular remodelling in rats, and inhibition of FoxO1 thus offers a potential therapeutic option for diabetes-associated cardiovascular diseases.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Proteínas do Tecido Nervoso/genética , Remodelação Vascular/genética , Animais , Apoptose/genética , Biomarcadores , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Diabetes Mellitus Experimental , Angiopatias Diabéticas/metabolismo , Modelos Animais de Doenças , Imunofluorescência , Humanos , Imuno-Histoquímica , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Modelos Biológicos , Miócitos de Músculo Liso/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Ratos
7.
BMC Infect Dis ; 20(1): 414, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539714

RESUMO

BACKGROUND: Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis larval tapeworm infections in humans that severely impairs the health of affected patients in the northern hemisphere. METHODS: The expression levels of 20 cytokines associated with AE infection were measured by enzyme-linked immunosorbent assay, and the correlations between these cytokines were analysed in the R programming language. RESULTS: Serum cytokine levels differed among individuals in both the AE patient and healthy control groups. The results of the correlations among the cytokines showed obvious differences between the two groups. In the AE patients group, Th1 and Th2 cytokines formed a more complicated network than that in the healthy control group. CONCLUSIONS: The altered correlations between Th1 and Th2 cytokines may be closely associated with AE infection, which may provide a new explanation for the essential differences between AE patients and healthy individuals.


Assuntos
Equinococose/imunologia , Equilíbrio Th1-Th2 , Adulto , Animais , Citocinas/sangue , Equinococose/sangue , Echinococcus multilocularis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
J Integr Plant Biol ; 62(7): 912-926, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31490027

RESUMO

Adventitious root (AR) formation from leafy stem cuttings is critical for breeding of many forest and horticultural species. In addition to the plant hormone auxin, wound-induced signaling caused by the cutting excision is also essential for AR initiation. Here we found that reactive oxygen species (ROS) are rapidly generated at the excision site as a wound-induced signal and propagated throughout the hypocotyl cutting after excision of the Arabidopsis (Arabidopsis thaliana) primary root. ROS propagation was not observed in the presence of an NADPH oxidase inhibitor (diphenylene iodonium chloride) or in a knockout mutant of the NADPH oxidase gene respiratory burst oxidase homolog protein D (RBOHD). Respiratory burst oxidase homolog protein D was specifically upregulated in hypocotyl cuttings at 0.5 h post excision (hpe). Together, these data suggest that RBOHD mediates ROS propagation in hypocotyl cuttings. We also found that auxin levels increased significantly in the shoot apex at 5 hpe and at the base of the cutting at 6 hpe; these effects were blocked by treatment with ROS scavengers. Consistent with this, transcript levels of auxin biosynthesis and polar-transport genes generally increased between 1 to 6 hpe. Collectively, our results suggest that wound-induced ROS participate in AR induction through regulation of auxin biosynthesis and transport.


Assuntos
Arabidopsis/metabolismo , Hipocótilo/metabolismo , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico/genética , Vias Biossintéticas/genética , Parede Celular/enzimologia , Fluorescência , Regulação da Expressão Gênica de Plantas , Mutação/genética , NADPH Oxidases/metabolismo , Peroxidase/metabolismo , Explosão Respiratória , Fatores de Tempo
9.
Clin Sci (Lond) ; 133(17): 1871-1881, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31434696

RESUMO

Emerging studies have demonstrated that microRNAs (miRs) participate in the development of multiple metabolic complications including cardiovascular diseases. Among them, circulating level of liver-secreted miR-122 was closely correlated with several consequence of heart diseases in clinical studies, and overexpression of miR-122 impaired cardiomyocyte function. However, it was unknown whether miR-122 could regulate cardiac biology in obesity. Therefore, present study was to disclose the role of miR-122 in cardiac metabolic disorders and potential molecular mechanisms. Through utilizing clinical samples and high fat diet-fed mice, we investigated the physiological roles of miR-122 in obesity-related cardiomyopathy. Besides, present study explored the mitochondrial function under exosomal miR-122 stimulation in mouse primary cardiomyocytes. In clinical samples and obese mice, the circulating level of exosomal miR-122 was positively correlated with cardiac dysfunctional parameters, including reduction in ejection fraction (EF) and increased levels of NT-proBNP. Human plasma exosomes transported miR-122 into mouse primary cardiomyocytes, and impaired mitochondrial ATP production and oxygen consumption, whereas miR-122 sponge improved these inhibitory effects. In dietary-induced mice, increased hepatic and circulating exosomal miR-122 deteriorated cardiac structure and functional index, and inhibited mitochondrial function. Liver-specific blockage of miR-122 attenuated abnormal cardiac remodeling. Mechanistically, miR-122 directly bound and suppressed mitochondrial protein ADP-ribosylation factor-like 2 (Arl-2) in vitro and in vivo Knockdown of Arl-2 abolished the mitochondrial benefits of miR-122 sponge in exosome-treated mouse primary cardiomyocytes.In conclusions, our present study firstly showed that liver-secreted exosomal miR-122 played a critical role in the development of metabolic cardiomyopathy, and miR-122/mitochondrial Arl-2 signaling affected cardiac energy homeostasis.


Assuntos
Cardiomiopatias/etiologia , Exossomos/metabolismo , Proteínas de Ligação ao GTP/metabolismo , MicroRNAs/metabolismo , Obesidade/complicações , Animais , Cardiomiopatias/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Obesidade/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
10.
Cell Physiol Biochem ; 51(2): 842-853, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30466081

RESUMO

BACKGROUND/AIMS: Increasing wall stress or biomechanical stretch experienced by arteries influences the initiation of atherosclerotic lesions. This initiation is mediated by Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway. In this study, the functional roles of YAP/TAZ proteins in the regulation of the stretch-mediated programing of human umbilical arterial smooth muscle cells (HUASMCs) to a proliferative phenotype were examined. METHODS: HUASMCs were seeded on a Matrigel-coated silicone chamber and subjected to biomechanical stretch for 24 h after 48 h of growth. YAP/TAZ small interfering RNA was used to specifically knockdown YAP/ TAZ expression in HUASMCs. RESULTS: We observed that YAP/TAZ activation via biomechanical stretching is involved in the regulation of critical aspects of the HUASMC phenotypic switch. YAP/TAZ knockdown significantly attenuated the stretch-induced proliferative and pro-inflammatory phenotypes in HUASMCs. Furthermore, treatment with atorvastatin, an anti-atherosclerotic drug, attenuated the stretch-induced phenotypic switch of HUASMCs from the contractile to synthetic state by suppressing YAP/TAZ expression. Additional investigations demonstrated the role of stretch in inhibiting the Hippo pathway, leading to the activation of PI3-kinase (PI3K) and phosphoinositide dependent kinase (PDK1); the key molecule for the regulation of the PDK1 and Hippo complex interaction was Sav1. These results showed the importance of YAP/TAZ activation, induced by biomechanical stretch, in promoting atheroprone phenotypes in HUASMCs. CONCLUSION: Taken together, our findings revealed a mechanism by which YAP/TAZ activation contributes to the pathogenesis of atherosclerosis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fosfoproteínas/metabolismo , Fatores de Transcrição/metabolismo , Remodelação Vascular , Aciltransferases , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Atorvastatina/farmacologia , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Movimento Celular , Proliferação de Células , Regulação da Expressão Gênica/efeitos dos fármacos , Via de Sinalização Hippo , Humanos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Mecânico , Fatores de Transcrição/antagonistas & inibidores , Artérias Umbilicais/citologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteínas de Sinalização YAP
11.
Cell Physiol Biochem ; 49(3): 1180-1196, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30196277

RESUMO

BACKGROUND/AIMS: IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 on dendritic cells (DCs) remains to be clarified. METHODS: In this study, we investigated the expression of IL-35 in DCs after stimulation with LPS utilizing enzyme linked immunosorbent assay(ELISA), quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, and the influence of IL-35 on the maturation and function of DCs by mixed lymphocyte reaction assay and flow cytometry. We further examined the regulation of IL-35 in DCs by the microRNA let-7i (let-7i) via transfected with let-7i mimic, inhibitor or suppressor of cytokine signalling 1 (SOCS1) siRNA. IL-35-overexpressing DCs were transfused into BALB/c recipients with C57BL/6 heart transplantations to verify the role of immune tolerance in transplantation. RESULTS: The results showed that IL-35 expression was significantly up-regulated following lipopolysaccharide (LPS)-induced DC maturation. Overexpression of IL-35 suppressed DC maturation, promoted the secretion of anti-inflammatory cytokines, and subsequently affected the balance between Treg and Th17 cells. IL-35 expression in DCs was regulated by let-7i, which targets SOCS1. The transfusion of IL-35-transfected DCs induced Treg generation in mice and prolonged cardiac allograft survival. CONCLUSION: Our data demonstrated that IL-35 induces tolerogenic DCs which are capable of alleviating allograft rejection. Clinical application of IL-35-treated DCs might be a promising approach for eliciting cardiac allograft immune tolerance.


Assuntos
Células Dendríticas/transplante , Sobrevivência de Enxerto/fisiologia , Transplante de Coração , Interleucinas/metabolismo , Animais , Antagomirs/metabolismo , Citocinas/análise , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Interleucinas/genética , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Supressoras da Sinalização de Citocina/antagonistas & inibidores , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/citologia , Células Th17/imunologia , Células Th17/metabolismo , Transplante Homólogo
12.
Biochem Biophys Res Commun ; 505(1): 242-248, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30243718

RESUMO

In diabetic cardiomyopathy, mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation, leading to metabolic disturbances. Fibroblast growth factor 19 (FGF19) acts as a metabolic regulator and may have a cardioprotective role on diabetic cardiomyopathy. In this study, we investigated the effects of FGF19 on energy metabolism. FGF19 treatment of diabetic hearts exhibited higher glucose uptake and lower lipid profiles, suggesting changes in energy metabolism. The protective effects of FGF19 prevented ventricular dysfunction in diabetic hearts and improved mitochondrial function by the upregulation of PGC-1α expression. On the other side, knockdown of PGC-1α by siRNA attenuated the effects of FGF19 on the enhancement of mitochondrial function and energy efficiency. Taken together, these results show that FGF19 exhibited improved mitochondrial efficiency, which might be associated with higher cardiac contractility in diabetic hearts. It is also of note that modulation of PGC-1α, which is responsible for the activation by FGF19, may be a therapeutic target for diabetic cardiomyopathy.


Assuntos
Cardiomiopatias Diabéticas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/farmacologia , Coração/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Animais , Células Cultivadas , Cardiomiopatias Diabéticas/fisiopatologia , Fatores de Crescimento de Fibroblastos/administração & dosagem , Coração/fisiopatologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Interferência de RNA , Ratos Sprague-Dawley
13.
J Vasc Res ; 54(1): 13-21, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28118639

RESUMO

Cables1 (Cdk5 and Abl enzyme substrate 1) is a vital cell cycle regulator and a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Here, we report on the critical role of the Cables1/p21 pathway, which inhibits cell proliferation and induces cell senescence in human umbilical vein endothelial cells. Moreover, we confirmed that silencing of Cables1 promoted cell proliferation as well as increased resistance to angiotensin II-induced senescence, at least in part, by altering Cables1 activation. We further demonstrated that knockdown of p21 reverses Cables1-mediated cell growth inhibition and cell senescence. Taken together, these results suggest that the Cables1/p21 pathway has a strong effect on the induction of cell senescence and inhibition of cell growth, and acts as a novel regulatory mechanism in which p21 is probably one of several downstream effector molecules to mediate Cables1.


Assuntos
Angiotensina II/farmacologia , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ciclinas/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fosfoproteínas/metabolismo , Proteínas de Transporte/genética , Células Cultivadas , Ciclinas/genética , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Fosfoproteínas/genética , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Transfecção
14.
Artigo em Zh | MEDLINE | ID: mdl-30141871

RESUMO

Objective: To investigate the prevalence of echinococcosis in Yushu Prefecture of Qinghai Province in 2012. Methods: Two to three towns were selected in each of Chengduo, Nangqian, Qu malai, Yushu, Zaduo and Zhiduo Counties from June to August in 2012. Ultrasound examination was conducted for residents aged over 1 year, and ELISA was performed to detect serum antibody against Echinococcus. Visceral dissection was performed to detect hydatid infection in rodents and livestock. ELISA was used to detect Echinococcus antigen in collected dog feces. Results: A total of 7 025 residents received ultrasound examination, of whom 319 showed hydatid cysts with a morbidity rate of 4.54%. ELISA showed a serum antibody positive rate of 16.38% (457/2 790). The mobidity of hydatid disease was highest in Chengduo County (7.41%, 181/2 444), and the rate of serum antibody was highest in Yushu County (23.18%, 127/548). The morbidity and serum antibody in males were 3.91% (118/3 018) and 13.93% (172/1 235) respectively, and those in females were 5.02% (201/4 007) and 18.33% (285/1 555). In terms of age distribution, the morbidity was relatively higher in residents of 60- (8.39%, 38/453) and 40- years (6.61%, 67/1 014); and the rate of serum antibody was highest in residents over 70 years (33.93%, 19/56). In terms of occupation, the morbidity was relatively higher in herdsmen (5.28%, 252/4 777), Herdsmen-peasants (6.52%, 24/368), and religious workers(3.37%, 11/326), while the rate of serum antibody was relatively higher in children(24%, 6/25), religious workers (18.79%, 31/165) and herdsmen(18.34%, 328/1 788). In terms of education level, the morbidity and the rate of serum antibody were both highest in the uneducated(5.04%, 41/4 779; 18.34%, 359/1 958, respectively). In terms of residential pattern, the morbidity and the rate of serum antibody were both highest in those who were settled in winter and nomadic in summer (8.25%, 227/2 753; 19.48%, 158/811, respectively). There were significant differences in the morbidity and the rate of serum antibody in aspects of residential region, sex, age, occupation, education level and residential pattern (P<0.05 or P<0.01). In 872 rodents detected, the Echinococcus hydatid rate was 0.46% (4/872), while in 809 cattle and sheep detected, the Echinococcus hydatid rate was 10.14% (82/809). The fecal antigen positive rate in 838 samples of dog feces was 10.74%(90/838). Conclusion: It shows a high morbidity of hydatid diesease and serum antibody positive rate in residents, a high Echinococcus hydatid rate in cattle and sheep, and a high fecal antigen positive rate in dogs in Yushu Prefecture.


Assuntos
Equinococose , Echinococcus , Adulto , Distribuição por Idade , Idoso , Animais , Antígenos de Helmintos , Bovinos , Meio Ambiente , Ensaio de Imunoadsorção Enzimática , Fezes , Feminino , Humanos , Lactente , Gado , Prevalência , Estações do Ano , Ovinos , Inquéritos e Questionários , Ultrassonografia
15.
Artigo em Zh | MEDLINE | ID: mdl-26672216

RESUMO

OBJECTIVE: To understand the status of echinococcosis in Maqing County of Qinghai Province in order to facilitate echinococcosis control in this region. METHODS: Ultrasonic scanning and indirect hemagglutination assay were used to detect echinococcosis infection in residents >1 year old, according to the People's Republic of China Health Industry Standard--Diagnostic Criteria for Hydatid Disease (WS257-2006). Meanwhile, ELISA was used o detect the Echinococcus antigen in dog's feces collected in Youyun, Dangluo and Xiadawu townships. RESULTS: Ultrasonic scanning showed that the prevalence of hydatid disease in the residents was 7.4% (116/1 561), cystic hydatid disease 5.3% (82/1 561), alveolar hydatid disease 2.2% (34/1 561). The serum positive rate in human population was 23.8%(307/1 288). Of the 82 cases of cystic hydatid disease, 23 cases (28.1%) had the hydatid cyst with a diameter of >10 cm. The prevalence in males and females in the county was 5.3% (40/753) and 9.4% (76/808), respectively (P<0.05). Among populations with different occupations, the highest prevalence of hydatid disease fell into houseworkers (11/61, 18.0%), monks (5/41, 12.2%) and herdsmen (84/758, 11.1%). Among the age groups, the groups of >60 years (24/132, 18.2%) and 30-40 years (31/302, 10.3%) had higher prevalence of hydatid disease. The three townships with the higher prevalence were Youyun (29/247, 11.7%), Changmahe (6/63, 9.5%) and Dangluo (54/645, 8.4%). Of the 199 samples of dog's feces, 54 were positive for Echinococcus antigens (27.1%), with a positive rate of 40.4% (23/57) in Youyun towship, being significantly higher than in the other two (P<0.05). CONCLUSION: Maqin county is a co-endemic area of cystic echinococcosis and alveolar echinococcosis. The prevalence is higher in females and those over 60 years-old.


Assuntos
Equinococose , Echinococcus , Animais , China , Cães , Ensaio de Imunoadsorção Enzimática , Fezes , Feminino , Testes de Hemaglutinação , Humanos , Lactente , Masculino , Prevalência
16.
Micromachines (Basel) ; 15(8)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39203680

RESUMO

The key technologies for the ultrathin small outline package (TSOP) of large-sized high-speed chips have been designed and developed in this paper. The designing techniques, such as a 25 µm precise positioning dice attaching technique, a lead frame unit structure without a base island, and a lead co-plane layout inside the frame, were developed. The TSO package outline with a large number of leads, a frame unit arrangement, and a frame distribution with a base island and without one were improved. The technological problems, including the reduction in thickness, wafer cutting, chip sticking bonding, and plastic sealing, were successfully solved. The designed large-sized package products have many advantages, such as high availability, low cost, high reliability, and a short production cycle. This package technique can be widely used in various intellectual application regions.

17.
Micromachines (Basel) ; 15(7)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39064361

RESUMO

A miniaturized and wideband four-port multiple-input multiple-output (MIMO) antenna pair for Wi-Fi mobile terminals application is proposed. The proposed antenna pair consists of four multi-branch antenna elements arranged orthogonally, with an overall size of 40 × 40 × 3.5 mm3 and each antenna element size of 15.2 × 3.5 mm × 0.8 mm3. The performance of the proposed antenna shows the advantages of a wide frequency band, low mutual coupling, high efficiency, and a compact structure. The wideband characteristics of the antenna elements are achieved through multi-mode resonance. The suppression of coupling is accomplished by strategically positioning the four compact antenna elements to ensure their maximum radiation directions are orthogonal, thus eliminating the need for an additional decoupling structure. In this paper, the proposed antenna is optimized in terms of the parameters then simulated and measured. The simulated results illustrate that an impedance bandwidth of the antenna is about 15% (5.06~5.88 GHz) with S11 < -10 dB, excellent port isolation exceeds 20 dB between all ports, a high radiation efficiency ranges from 51.2% to 89.9%, the maximum gain is 4.5 dBi, and the ECCs are less than 0.04. The measured results show that the -10 dB impedance bandwidth of the antenna is about 13% (5.13~5.80 GHz), the isolation between the antenna elements is better than 21 dB, the radiation efficiency ranges from 51.8% to 92.3%, the maximum gain is 5.3 dBi, and the ECCs are less than 0.05. The proposed four-port MIMO antenna works on the 5G LTE band 46 and Wi-Fi 6E operating bands. As a mobile terminal antenna, the proposed design scheme demonstrates excellent performance and applicability, fulfilling the requirements for 5G mobile terminal applications.

18.
Genes Dis ; 11(6): 101100, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39281832

RESUMO

High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

19.
Commun Biol ; 7(1): 1097, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242698

RESUMO

The Qinghai-Tibet Plateau (QTP), renowned for its exceptional biological diversity, is home to numerous endemic species. However, research on the virology of vulnerable vertebrates like yaks remains limited. In this study, our objective was to use metagenomics to provide a comprehensive understanding of the diversity and evolution of the gut virome in yak populations across different regions of the QTP. Our findings revealed a remarkably diverse array of viruses in the gut of yaks, including those associated with vertebrates and bacteriophages. Notably, some vertebrate-associated viruses, such as astrovirus and picornavirus, showed significant sequence identity across diverse yak populations. Additionally, we observed differences in the functional profiles of genes carried by the yak gut virome across different regions. Moreover, the virus-bacterium symbiotic network that we discovered holds potential significance in maintaining the health of yaks. Overall, this research expands our understanding of the viral communities in the gut of yaks and highlights the importance of further investigating the interactions between viruses and their hosts. These data will be beneficial for revealing the crucial role that viruses play in the yak gut ecology in future studies.


Assuntos
Microbioma Gastrointestinal , Metagenômica , Viroma , Animais , Bovinos , Microbioma Gastrointestinal/genética , Viroma/genética , Tibet , Metagenoma
20.
Sci Rep ; 13(1): 1924, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732551

RESUMO

To provide guidance for plague surveillance and a reliable basis for plague prevention and control, we analyzed the habitat characteristics of Himalayan marmots, developed Himalayan marmot information collection system V3.0 based on global navigation satellite system (GNSS), remote sensing, and geographic information system ("3S") technology, and drew a predictive spatial distribution map of Himalayan marmots in Qinghai Province. Field survey data of 352 marmot plague sites in Qinghai Province were collected in 2014, and the data from 80 sample sites were included. The Himalayan marmot habitat characteristics were analyzed based on "3S" technology using five environment variables (elevation, slope, aspect, vegetation cover, and grass type) and the geographical coordinates. Himalayan marmot information collection system V3.0, which has been approved by the National Copyright Administration of the People's Republic of China (No.00764743), was used to draw a predictive spatial distribution map of Himalayan marmots in Qinghai province. Moreover, from 2015 to 2017, positioning data of the plague-foci and plague-free areas in Qinghai Province were collected using GNSS receptor for field validations to verify the accuracy of the marmot predictive spatial distribution map. Elevation, slope, vegetation cover, and grassland type were identified as important environmental factors that determine the spatial distribution of Himalayan marmots. The suitable range of environmental features was 3400-4600 m elevation, 5°-20° slope, 0.60-1.00 vegetation cover, and alpine meadows. The Himalayan marmot predictive spatial distribution map in Qinghai Province based on "3S" technology and marmot information collection system V3.0 had a spatial resolution of 30 m. Field validation in areas of Qinghai Province revealed a prediction accuracy and mean absolute error of 0.8669 and 0.1331, respectively, which indicated excellent prediction accuracy. This study greatly improved the work efficiency of plague surveillance and effectively reduced the work intensity of researchers. Application of "3S" technology and marmot information collection system V3.0 has improved the data collection efficiency, provided new technical means for plague investigation and research, and provided a reference for development of plague surveillance programs. The research results will play a positive role in promoting the improvement and perfection of plague prevention and control strategies in Qinghai province and even in China.


Assuntos
Ecossistema , Marmota , Animais , Humanos , China/epidemiologia , Sistemas de Informação Geográfica , Poaceae
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