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Objective: To investigate the effects of Moringa Oleifera Leaf Extract (MOLE) plus rosiglitazone (RSG) on glucose and lipid metabolism, serum leptin, and the Akt/GSK3ß/ß-Catenin signaling pathway in type 2 diabetic (T2D) rats. Methods: Sixty male Sprague-Dawley (SD) rats were randomly divided into six groups: the normal group, the model group, the RSG group, the low- and high-dose MOLE group, and the MOLE+RSG group. The normal group was fed a standard rat diet, while the other groups were given a single intraperitoneal injection of low-dose streptozomycin (STZ) (35 mg/kg) and fed a high-sugar and high-fat diet. After 8 weeks, the treatment outcomes were evaluated by measuring key parameters of blood glucose and lipid metabolism and the protein kinase B (AKT) / Glycogen synthase kinase 3beta (GSK3ß) /ß-Catenin signaling pathway in the T2D rats. Results: Compared with the normal group, the model group showed significantly increased levels of blood glucose, blood lipids, serum leptin, free fatty acid (FFA), and tumor necrosis factor-α (TNF-α). Compared with the model group, the RSG, low-dose MOLE, and high-dose MOLE groups displayed effective control of blood glucose, blood lipids, serum leptin, FFA, and TNF-α. The MOLE+RSG group surpassed the RSG group in regulating glucose, lipid metabolism, and serum leptin levels in T2D rats. In addition, the MOLE+RSG group also had superiority over the RSG group in activating the AKT/GSK3ß/ß-Catenin pathway. Conclusion: MOLE plus RSG can effectively reduce blood glucose and blood lipids in T2DM rats.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Moringa oleifera , Ratos , Masculino , Animais , Rosiglitazona/uso terapêutico , Glucose/metabolismo , Glicemia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , Moringa oleifera/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/metabolismo , beta Catenina/uso terapêutico , Leptina/metabolismo , Leptina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Metabolismo dos Lipídeos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Ratos Sprague-Dawley , Lipídeos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêuticoRESUMO
Adipose tissue remodelling is considered a critical pathophysiological hallmark of obesity and related metabolic diseases. Berberine (BBR), a natural isoquinoline alkaloid, has potent anti-hyperlipidaemic and anti-hyperglycaemic effects. This study aimed to explore the role of BBR in modulating adipose tissue remodelling and the underlying mechanisms. BBR protected high fat diet (HFD)-fed mice against adiposity, insulin resistance and hyperlipidemia. BBR alleviated adipose tissue inflammation and fibrosis by inhibiting macrophage infiltration, pro-inflammatory macrophage polarization and the abnormal deposition of extracellular matrix, and the effect was mediated by BBR directly binding and activating the deacetylase Sirtuin 3 (SIRT3) and suppressing the activation of the mitogen-activated protein kinases and nuclear factor-κB signalling pathways. Furthermore, BBR decreased microRNA-155-5p secretion by macrophages, which in turn ameliorated liver injury. Moreover, BBR mitigated inflammatory responses in both LPS-stimulated macrophages and TNF-α-treated adipocytes and suppressed macrophage migration towards adipocytes by activating SIRT3. Collectively, this study revealed that BBR improved adipose tissue remodelling, and subsequently inhibited the secretion of microRNA-155-5p by macrophages, which alleviated adiposity, insulin resistance and liver injury in obese mice. The modulation of adipose tissue remodelling by activating SIRT3 could contribute to the anti-hyperlipidemic and anti-hyperglycemic effects of BBR.
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Berberina , Resistência à Insulina , MicroRNAs , Sirtuína 3 , Tecido Adiposo , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Dieta Hiperlipídica , Inflamação , Camundongos , MicroRNAs/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismoRESUMO
Interleukin-1ß (IL-1ß), a key pro-inflammatory cytokine, is majorly produced by macrophages through NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, which has been identified as the culprit to deteriorate the inflammatory crosstalk between macrophages and adipocytes. Ainsliadimer C (AC) is a disesquiterpenoid isolated from Ainsliaea macrocephala. In the current study, we investigated the effects of AC on adipose tissue inflammation in co-culture of macrophages and adipocytes in vitro as well as in LPS-treated mice in vivo. We showed that AC (20-80 µM) dose-dependently inhibited the secretion of IL-1ß from LPS plus ATP-stimulated THP-1 macrophages by inhibiting the activation of NLRP3 inflammasome. Furthermore, we found that AC treatment activated NAD+-dependent deacetylase Sirtuin 1 (SIRT1), resulting in reduced acetylation level of NLRP3. Molecular modeling analysis revealed that binding of AC to sirtuin-activating compound-binding domain increased the affinity of the substrate to the catalytic domain of SIRT1. Moreover, AC (80 µM) significantly attenuated macrophage-conditioned medium-induced inflammatory responses in 3T3-L1 adipocytes. In LPS-induced acute inflammatory mice, administration of AC (20, 60 mg·kg-1·d-1, ip) for 5 days significantly suppressed the pro-inflammatory cytokine levels in serum and epididymal white adipose tissue (eWAT), attenuated macrophage infiltration into eWAT, and mitigated adipose tissue inflammation. The beneficial effects of AC were blocked by co-administration of a selective SIRT1 inhibitor EX-527 (10 mg·kg-1·d-1). Taken together, AC suppresses NLRP3-mediated IL-1ß secretion through activating SIRT1, leading to attenuated inflammation in macrophages and adipose tissue, which might be a candidate to treat obesity-associated metabolic diseases.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Tecido Adiposo/metabolismo , Animais , Citocinas/metabolismo , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos NOD , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sirtuína 1/metabolismoRESUMO
OBJECTIVE: To explore the values of serum copper and serum free copper in the diagnosis of Wilson's disease (WD), its carrier and viral hepatitis and explore the guiding significance of monitoring serum copper in the treatment of WD. METHODS: A total of 80 WD patients (hepatic type, n = 60; encephalic type, n = 20), 30 carriers, 20 patients with viral hepatitis were enrolled and their levels of serum copper were determined. The neural symptoms were scored by modified Young grade. Hemogram, hepatic functions, blood clotting functions, serum copper and urinary copper were tested throughout all 8 courses of treatment with sodium dimercaptopropane sulfonate (DMPS). The patients were treated with zinc after discharging. All data were analyzed. RESULTS: The free serum copper increased in the patients with WD (0.17 mg/L ± 0.04 mg/L), carriers (0.13 mg/L ± 0.03 mg/L) and severe viral hepatitis (0.12 mg/L). A slight increase was also observed in the WD carriers. The level of serum copper was correlated with hepatic functions but not with the severity of neural symptoms. The serum copper increased in the patients with no improvement of neural symptoms. However, the serum copper decreased in the WD patients with the improvement of neural symptoms. The serum copper was stabilized at approximately 0.2 mg/L during the long-term treatment period. CONCLUSION: There is auxiliary diagnosis significance of serum copper in the determination of WD. Hepatic functions in hepatic type WD affect the level of serum copper. The serum copper of encephalic type WD can not indicate the severity of neural symptoms. The elevated level of serum copper indicates a poor prognosis. The serum copper is an effective marker in monitoring the development and therapeutic efficacy of the disease.
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Cobre/sangue , Degeneração Hepatolenticular/sangue , Heterozigoto , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Masculino , Adulto JovemRESUMO
Objective: To investigate the effects of Moringa leaves on the cognitive dysfunction and apoptosis of hippocampal neurons in diabetic rats induced by streptozotocin (STZ). Methods: Fifty male SD rats were selected, and 10 rats were randomly selected as the control group. The other 40 rats were treated with STZ at the dose of 25 mg/kg by intraperitoneal injection. The 40 diabetic rats were randomly divided into model group, Moringa oleifera low-dose, medium-dose and high-dose group. The rats in Moringa oleifera groups were treated with Moringa oleifera at the doses of 2.0, 4.0 and 8.0 g/kg by gavage, the control group and model group were treated with the same amount of normal saline once a day, for 8 weeks. Morris water maze test was used to evaluate the learning and memory ability of rats. Pathological changes of hippocampal neurons and expressions of Bax, caspase-3 and bcl-2 protein in each group were observed by the sections were stained with HE staining and immunohistochemistry. Enzyme linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rat. Results: compared with the control group, the blood glucose of the model group was increased significantly (Pï¼0.01), and the blood insulin level was decreased significantly (Pï¼0.05); compared with the model group, the blood glucose values of Moringa oleifera groups were decreased significantly (Pï¼0.05, Pï¼0.01), and the blood insulin levels of middle and high dose Moringa oleifera group were increased significantly (Pï¼0.05, Pï¼0.01). There was no significant difference in FBG and INS among the three groups (Pï¼0.05). In Morris water maze test, compared with the model group, the latency of Moringa oleifera groups was significantly shorter (Pï¼0.05); the residence time in target quadrant of Moringa oleifera groups with different doses was significantly prolonged (Pï¼0.05). Compared with the model group, the contents of TNF - α, IL-6 and protein expression in low, medium and high dose groups of Moringa oleifera were decreased significantly (Pï¼0.05). HE staining and immunohistochemical staining results showed that Moringa oleifera medium dose group was positive, brown yellow, fine granular, compared with the model group. The number of neuronal apoptosis was significantly reduced in the middle dose group (53.21±7.19,Pï¼0.01); the protein expressions of Bax, caspase-3 and the ratio of Bax/Bcl-2 in hippocampus were significantly decreased in the middle dose group (Pï¼0.05). Conclusion: The mechanisms of Moringa leaves on the cognitive dysfunction and apoptosis of hippocampal neurons may be related to regulating the protein expressions of Bax, Bcl-2 and Caspase-3, reducing the contents of inflammatory factors TNF-α and IL-6.
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Apoptose , Diabetes Mellitus Experimental , Medicamentos de Ervas Chinesas/farmacologia , Moringa/química , Neurônios/citologia , Animais , Cognição , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo/citologia , Neurônios/efeitos dos fármacos , Folhas de Planta/química , Ratos , Ratos Sprague-DawleyRESUMO
A novel biochar was prepared by modification with corn straw, ethylene triamine, and carbon disulfide, and its adsorption properties and stability with respect to heavy metal ions in single and mixed systems (Pb2+, Ni2+, and Cd2+) were investigated. Characterization analysis confirmed the successful modification of an amine-sulfur double group on the surface of the biochar, which had abundant functional groups with a large specific surface area. Adsorption experiments under the single system indicated that the adsorption equilibrium time was 4 h and the optimum dosages were 1, 0.8, and 1.2 g·L-1. The adsorption met the conditions of the quasi-second-order kinetic equation. Under the ternary system, the adsorption equilibrium time was reduced to 1.5 h, the optimum dosages were 0.4, 1.6, and 0.8 g·L-1, and the adsorption sequence was Pb2+ > Cd2+ > Ni2+. The total amount of adsorption was 0.67 mmol·g-1, which was higher than that of single heavy metal ions, indicating that amine-sulfur modified straw biochar (BC-SN) has an improved treatment effect on polluted water under the coexistence of three heavy metal ions. The Pb2+ and Cd2+ adsorbed by the biochar was stably bound in the form of heavy metal sulfide and a chelated amino group. In contrast, the adsorption of Ni2+ was via the mixed adsorption of various functional groups. When Pb2+ and Cd2+ compete for adsorption, the binding energy is higher and adsorption stability is more reliable.
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Objective: To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 µg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Results: Compared with the control group, the blood glucose levels of other groups were increased significantly (Pï¼0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (Pï¼0.05, Pï¼0.01). The insulin level of high dose leptin group decreased significantly (Pï¼0.01). There was no significant difference in FBG and INS among the three groups (Pï¼0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (Pï¼0.05, Pï¼0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (Pï¼0.05), HDL-C level of high dose group was increased significantly (Pï¼0.01). Compared with different dose groups, the high dose of leptin (100 µg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (Pï¼0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. Conclusion: The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 µg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.
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Diabetes Mellitus Experimental , Leptina , Metabolismo dos Lipídeos , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Inflamação , Leptina/administração & dosagem , Leptina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
OBJECTIVE: We produced a large-animal model of myocardial infarction induced by transcatheter embolization of the left coronary artery using a gelatin sponge. METHODS: Seven pigs underwent transcatheter embolization of the left anterior descending artery (LAD) using gelatin sponge to produce anteroapical myocardial infarction (MI). 4 weeks later, Echocardiography, Coronary angiography and Pathology was performed, and the data were compared with those of the control group (n = 6). RESULTS: The procedure mortality was 1 of 7. In the MI group, the LV end-diastolic dimension increased (control versus MI: 37.0 mm +/- 3.4 mm and 50.8 mm +/- 6.1 mm, P < 0.01), the ejection fraction (EF) decreased (control versus MI: 62.3% +/- 2.9% and 36.6% +/- 2.1%, P < 0.001). Coronary angiography revealed the LAD remained occluded. The postmortem specimen showed a transmural MI scar in the anteroseptal and apical regions in the MI group and the LV volumes at 30 mm Hg were 81.4 ml +/- 4.3 ml, the scar areas were 18.4% +/- 1.6% of total left ventricular free wall and the scar thickness was 3.5 mm +/- 0.8 mm. Histologic samples in the MI group stained with Masson's trichrome showed massive fibrosis in the border zone and patchy fibrosis in the remote region in the LV free wall, whereas the control group showed no fibrosis. CONCLUSION: This pig model of myocardial infarction is reliable, reproducible, and similar to the human condition, amenable to investigate other investigation.
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Modelos Animais de Doenças , Infarto do Miocárdio , Animais , Vasos Coronários , Gelatina , Infarto do Miocárdio/etiologia , Poríferos , SuínosRESUMO
The technology of steady combustion in a new type of rotary incinerator is firstly discussed. The formation and control of HCl, NOx and SO2 during the incineration of sampled municipal organic solid waste are studied with the incinerator. Results showed that the new model of rotary incinerator can effectively control and reduce the pollutant formations by post combustion.