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1.
Arch Microbiol ; 204(5): 257, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416536

RESUMO

In recent years, 16S ribosomal DNA (16S rDNA) sequencing has been widely developed. In the present study, we investigated the changes of fecal flora analyzed by sequencing of 16S rDNA and the alteration of blood biochemical indexes in cats during diarrhea. Seven normal fecal samples and seven fecal samples of British Shorthair cats with bacterial diarrhea about 6 months old were collected. The 16S rDNA V3 region of the bacteria was amplified for high-throughput sequencing. Finally, species analysis at various levels was performed. At the same time, samples of blood were taken to examine the changes of biochemical indexes in cats with diarrhea. The abundance and diversity of microflora in the healthy group were greater than those in the diarrhea group. The normal floras in the feces of healthy cats were Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria. The content of Proteobacteria and Firmicutes varied greatly in diarrheal cats. In addition, the number of white blood cells, lymphocytes, neutrophils, and globulin were increased in cats with diarrhea, whereas albumin level was decreased in diarrheal cats. In conclusion, the present study suggests 16SrDNA technology showed that the intestinal Proteus was abundant, and the content of Firmicutes was scarce in cats with diarrhea. Escherichia-Shigella was the main pathogens in this sample. Rapid blood biochemical tests may help clinicians to assess the severity and prognosis of cats with diarrhea.


Assuntos
Bactérias , Diarreia , Animais , Bactérias/genética , Gatos , DNA Ribossômico/genética , Diarreia/microbiologia , Diarreia/veterinária , Fezes/microbiologia , Firmicutes/genética , Proteobactérias/genética , RNA Ribossômico 16S/genética
2.
J Org Chem ; 87(5): 2740-2747, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35089023

RESUMO

A novel and mild metal-free catalyzed radical-mediated cascade spirocyclization of N-benzylacrylamides with polyhaloalkanes is proposed for the preparation of polyhalo-substituted azaspirocyclohexadienones. Notably, polyhaloalkanes are employed as efficient alkyl radical sources via the cleavage of C(sp3)-H bonds. This protocol undergoes a cascade radical addition and intramolecular cyclization/dearomatization process, and enables the easy construction of multiple chemical bonds and a spiro ring in a single reaction.


Assuntos
Compostos de Espiro , Ciclização , Radicais Livres , Compostos de Espiro/química
3.
Mol Biol Rep ; 49(10): 9195-9204, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35819554

RESUMO

BACKGROUND: Stomatitis is inflammation of the oral mucosa. Angiopoietin-like protein 4 (ANGPTL4) has pleiotropic functions both anti-inflammatory and pro-inflammatory properties. In the present study, we tested whether there is a correlation between increased ANGPTL4 expression and inflammation in stomatitis mice and the mechanisms involved. METHODS AND RESULTS: In this study, the oral mucosa of mice was burned with 90% phenol and intraperitoneal injection of 5-fluorouracil to establish the model of stomatitis mice. The pathological changes of stomatitis mice were observed by H&E staining of paraffin section. The expressions of cytokines and ANGPTL4 were detected by fluorescence quantitative PCR, and the protein levels of ANGPTL4 were detected by western blot. Compared with control group, the oral mucosal structure of model mice was damaged. The expression of ANGPTL4 were significantly increased concomitantly with elevated production of anti-inflammatory cytokine (peroxisome proliferator-activated receptor alpha) and pro-inflammatory cytokines [nuclear transcription factor-kappa B, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α] in mice with stomatitis. CONCLUSIONS: This study suggests that ANGPTL4 may be a double-edged sword in multiple inflammatory responses in stomatitis mice.


Assuntos
Angiopoietinas/metabolismo , Interleucina-6 , Estomatite , Proteína 4 Semelhante a Angiopoietina/genética , Angiopoietinas/genética , Animais , Citocinas , Fluoruracila , Inflamação , Interleucina-6/genética , Camundongos , NF-kappa B , PPAR alfa , Parafina , Fenóis , Fator de Necrose Tumoral alfa
4.
Exp Mol Pathol ; 103(3): 242-248, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29104012

RESUMO

Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.


Assuntos
Proteínas Semelhantes a Angiopoietina/sangue , Dislipidemias/sangue , Inflamação/sangue , Mastite/sangue , Proteína 3 Semelhante a Angiopoietina , Animais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/patologia , Feminino , Humanos , Inflamação/microbiologia , Inflamação/patologia , Lipase Lipoproteica/antagonistas & inibidores , Lipase Lipoproteica/sangue , Mastite/microbiologia , Mastite/patologia , Camundongos , N-Acetilgalactosaminiltransferases/metabolismo , Peroxidase/sangue , Staphylococcus aureus/patogenicidade , Triglicerídeos/sangue , Polipeptídeo N-Acetilgalactosaminiltransferase
5.
Can J Physiol Pharmacol ; 95(6): 625-633, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28177681

RESUMO

Impaired endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway induces atherogenesis. The present study examined whether icariin improves the eNOS/NO pathway to prohibit the atherogenesis of apolipoprotein E-null (ApoE-/-) mice. In vitro, primary human umbilical vein endothelial cells (HUVECs) were randomly divided into 7 groups: control; vehicle; icariin 10; lyphosphatidylcholine (LPC) group; LPC + icariin 1; LPC + icariin 3; and LPC + icariin 10. In vivo, 80 mice were separated randomly into 4 groups (n = 20): control, ApoE-/-, ApoE-/- + icariin 10, and ApoE-/- + icariin 30. ApoE-/- mice had significantly more atherosclerosis in the aortic root together with increased aortic ROS production, body mass, plasma triglyceride (TG) and total cholesterol (TC) concentration, decreased aortic eNOS expression, and plasma NO concentration. LPC (10 µg/mL) treatment induced a big decline in NO level in the conditioned medium and eNOS expression, and an increase in intracellular reactive oxygen species (ROS) production in HUVECs. Icariin treatment decreased atherogenesis, ROS production, body mass, plasma TG concentration, and plasma TC concentration, and increased NO concentration and eNOS expression. These findings suggested icariin could improve eNOS/NO-pathway to prohibit the atherogenesis of apolipoprotein E-null mice by restraining oxidative stress.


Assuntos
Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/prevenção & controle , Flavonoides/farmacologia , Deleção de Genes , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/genética
6.
World J Microbiol Biotechnol ; 31(8): 1235-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26003652

RESUMO

Mastitis is the inflammation of the mammary gland. Recent research has shown that Angiopoietin-like protein 2 (ANGPTL2) is a key inflammatory mediator. In the present study, we tested whether there is a correlation between increased ANGPTL2 expression and inflammation in response to Staphylococcus aureus in murine mastitis and the mechanisms involved. Thirty mice were divided into two groups: blank control group, challenged group. The entire infused mammary glands were removed to observe the changes of histopathology, myeloperoxidase (MPO) activity, production of tumour necrosis factor-α (TNF-α) and interleukin (IL)-6, and genes expression of ANGPTL2, TNF-α and IL-6. In challenged group, the structure of mammary glands was damaged and the large areas of cell fragments were observed. The MPO activity, IL-6 and TNF-α concentrations, ANGPTL2, IL-6, and TNF-α mRNA levels were significantly elevated in challenged group compared with blank control group. The present findings indicate ANGPTL2 may mediate the inflammation in murine mastitis through the activation of IL-6 and TNF-α.


Assuntos
Angiopoietinas/imunologia , Interleucina-6/genética , Mastite/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/fisiologia , Fator de Necrose Tumoral alfa/genética , Proteína 2 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Angiopoietinas/genética , Animais , Feminino , Humanos , Interleucina-6/imunologia , Mastite/genética , Mastite/microbiologia , Camundongos , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Fator de Necrose Tumoral alfa/imunologia
7.
Can J Physiol Pharmacol ; 92(2): 117-23, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24502634

RESUMO

Osteopontin (OPN), also called cytokine Eta-1, is a pro-inflammatory cytokine. Recent studies have shown that aldosterone increases OPN gene expression in endothelial cells. As a flavonoid compound, kaempferol has potent anti-inflammatory properties, but whether kaempferol regulates aldosterone signaling and aldosterone-induced gene expression is still unknown. Human umbilical vein endothelial cells (HUVECs) were pretreated with kaempferol (0, 1, 3, or 10 µmol/L) for 1 h prior to exposure to aldosterone (10(-6) mol/L) for 24 h. Aldosterone induced generation of reactive oxygen species; OPN and cluster of differentiation 44 gene expression; phospho-p38 MAPK and NF-κB binding activity. The effect of aldosterone was abrogated by kaempferol and spironolactone (10(-6) mol/L). The present results suggest that kaempferol exerts its anti-inflammatory properties via its inhibition of aldosterone signaling and aldosterone-induced gene expression in HUVECs.


Assuntos
Aldosterona/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Quempferóis/farmacologia , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , NF-kappa B/metabolismo , Osteopontina/genética , Osteopontina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
8.
Nat Commun ; 14(1): 2592, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147320

RESUMO

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/complicações , Isquemia Encefálica/terapia , Decúbito Inclinado com Rebaixamento da Cabeça , Estudos Prospectivos , Resultado do Tratamento , Acidente Vascular Cerebral/terapia
9.
Am J Physiol Renal Physiol ; 303(5): F757-65, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22718885

RESUMO

Heat shock protein (HSP)47 is a collagen-specific molecular chaperone that is essential for the biosynthesis of collagen molecules. It is likely that increased levels of HSP47 contribute to the assembly of procollagen and thereby cause an excessive accumulation of collagens in disease processes associated with fibrosis. Although HSP47 promotes renal fibrosis, the underlying mechanism and associated signaling events have not been clearly delineated. We examined the role of HSP47 in renal fibrosis using a rat unilateral ureteral obstruction model and transforming growth factor (TGF)-ß(1)-treated human proximal tubular epithelial (HK-2) cells. An upregulation of HSP47 in both in vivo and in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of HSP47 by short interfering RNA suppressed the expression of ECM proteins and PAI-1. In addition, TGF-ß(1)-induced HSP47 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of HSP47, the chaperoning effect of which on TGF-ß(1) would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.


Assuntos
Proteínas da Matriz Extracelular/biossíntese , Proteínas de Choque Térmico HSP47/fisiologia , Adulto , Animais , Linhagem Celular , Colágeno Tipo I/biossíntese , Colágeno Tipo IV/biossíntese , Fibrose , Humanos , Rim/metabolismo , Rim/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Inibidor 1 de Ativador de Plasminogênio/biossíntese , RNA Interferente Pequeno/farmacologia , Ratos , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima , Obstrução Ureteral/fisiopatologia
10.
Toxicol Appl Pharmacol ; 257(3): 405-11, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22005275

RESUMO

Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE(-/-)) mice treated or not with kaempferol (50 or 100mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE(-/-) mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE(-/-) mice.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Receptores de Hialuronatos/efeitos dos fármacos , Quempferóis/farmacologia , Osteopontina/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aterosclerose/patologia , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores de Hialuronatos/metabolismo , Quempferóis/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteopontina/sangue , Osteopontina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vasodilatação/efeitos dos fármacos
11.
J Hazard Mater ; 408: 124961, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33418518

RESUMO

The activation of carbon atoms in biochar is an important approach for realizing the reuse of discarded woody biomass resources. In this work, a strategy for the construction of carbon-based catalysts was proposed with Magnoliaceae root biomass as a carbon source, doped by SnS2 and further decorated with heteropoly acid. The introduction of SnS2 can activate the carbon atom and destroy the electronic inertness of the disordered biochar with 002 planes. In addition, the synergy between the Keggin unit of phosphotungstic acid and biochar/SnS2 can suppress recombination of e--h+ carriers. The adsorption and photocatalysis experiments results showed that the efficiency of removing As(III) by biochar/SnS2/phosphotungstic acid (biochar/SnS2/PTA) systems was 1.5 times that of biochar/SnS2 systems, and the concentration of total arsenic in the biochar/SnS2/PTA composite system gradually decreased during the photocatalysis process. The formation of As-POMs can simultaneously realize As(III) photooxidation and As(V) coprecipitation. The phase transfer of arsenic by As-POMs could significantly increase the As adsorption capacity. Specifically, the composites achieved the conversion of S atoms at the interface of biochar into SO4•- radicals to enhance the As(III) photooxidation performance.

12.
J Asian Nat Prod Res ; 11(7): 643-51, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20183301

RESUMO

Previous investigations have indicated that reduced erythrocyte deformability may be an important factor contributing to the development of atherosclerosis, and endogenous asymmetric dimethylarginine (ADMA) might be an important contributor to reduction of erythrocyte deformability in atherosclerosis. In this study, the effect of 3,4,5,6-tetrahydroxyxanthone (1), a kind of polyphenolic compound, on erythrocyte deformability in apolipoprotein E-deficient (apoE-/-) mice was evaluated. After treatment with compound 1 (10 or 20 mg/kg per day) for 4 weeks, erythrocyte deformability, antioxidant enzymes activity, erythrocyte dimethylarginine dimethylaminohydrolase (DDAH) activity, the plasma level of ADMA and malondialdehyde (MDA) level were determined. Treatment with compound 1 (10 or 20 mg/kg) increased erythrocyte deformability, antioxidant enzymes activity concomitantly, a decrease in the plasma levels of MDA and ADMA, and an increase in erythrocyte DDAH activity. The present result suggests that the beneficial effect of 1 on the erythrocyte deformability, besides inhibiting lipid peroxidation, may be related to reduction of ADMA concentration via an increase in DDAH activity.


Assuntos
Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/enzimologia , Xantonas/farmacologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Aterosclerose/etiologia , Catalase/metabolismo , Masculino , Malondialdeído/análise , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Superóxido Dismutase/metabolismo , Xantonas/química
13.
Fundam Clin Pharmacol ; 33(5): 549-557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30861604

RESUMO

Recent studies show that nitric oxide/asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase (NO/ADMA/DDAH) pathway may contribute to the development of sleep disorder. The objective of this study was to explore the inhibitory effect of procyanidin B2 from lotus seedpod (LSPC), a naturally occurring catechin compound, on insomnia and the mechanisms involved. The experiments were performed in brain from Sprague-Dawley rat control and insomniac rats treated or not with LSPC (15, 30, and 45 mg/kg, intragastrically) for 7 days. LSPC treatment reduced walking time and forelimb lifting-up frequency, cerebral levels of noradrenaline, glutamic acid, ADMA, sleep latency, and 8-isoprostane; increased sleep duration, cerebral concentrations of 5-hydroxytryptamine, γ-aminobutyric acid, and NO concomitantly with upregulated cerebral expression of DDAH 1, DDAH2, and neuronal NO synthases in insomniac rats. The present results suggest that LSPC may regulate NO/ADMA/DDAH pathway by inhibiting oxidative stress to treat insomnia in rats when sleep evaluation was achieved on the basis of behavioral criteria.


Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Biflavonoides/farmacologia , Catequina/farmacologia , Lotus/química , Óxido Nítrico/metabolismo , Proantocianidinas/farmacologia , Sementes/química , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Animais , Arginina/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sono/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono/metabolismo
14.
Life Sci ; 82(13-14): 699-707, 2008 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-18289604

RESUMO

Previous studies have shown that nitroglycerin (GTN) tolerance is closely related to an oxidative stress-induced decrease in activity of mitochondrial isoforms of aldehyde dehydrogenase (ALDH-2), and prolonged GTN treatment causes endothelial dysfunction. Asymmetric dimethylarginine (ADMA), a major endogenous NO synthase (NOS) inhibitor, could inhibit NO production and induce oxidative stress in endothelial cells. ADMA and its major hydrolase dimethylarginine dimethylaminohydrolase (DDAH) have recently been thought of as a novel regulatory system of endothelium function. The aim of the present study was to determine whether the DDAH/ADMA pathway is involved in the development of GTN tolerance in endothelial cells. Tolerance, reflected by the decrease in cyclic GMP (cGMP) production, was induced by exposure of human umbilical vein endothelial cells (HUVECs) to GTN (10 microM) for 16 h. While the treatment increased reactive oxygen species (ROS) production/malondialdehyde (MDA) concentration and decreased ALDH-2 activity as well as cGMP production, it markedly increased the level of ADMA in culture medium and decreased DDAH activity in endothelial cells. Exogenous ADMA significantly enhanced ROS production/MDA concentration and inhibited ALDH-2 activity, and overexpression of DDAH2 could significantly suppress GTN-induced oxidative stress and inhibition of ALDH-2 activity, which is also attenuated by L-arginine. Therefore, our results suggest for the first time that the endothelial DDAH/ADMA pathway plays an important role in the development/maintenance of GTN tolerance.


Assuntos
Aldeído Desidrogenase/fisiologia , Amidoidrolases/metabolismo , Arginina/análogos & derivados , Tolerância a Medicamentos , Células Endoteliais/efeitos dos fármacos , Nitroglicerina/farmacologia , Acetilcisteína/farmacologia , Aldeído Desidrogenase/antagonistas & inibidores , Aldeído-Desidrogenase Mitocondrial , Amidoidrolases/biossíntese , Arginina/metabolismo , Arginina/farmacologia , Linhagem Celular , GMP Cíclico/metabolismo , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Humanos , Peróxidos Lipídicos/metabolismo , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
15.
Obes Res Clin Pract ; 12(Suppl 2): 71-79, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28320596

RESUMO

OBJECTIVE: Previous investigations have shown that the peroxisome proliferator activated receptor beta/delta (PPAR/)-angiopoietin-like protein 4 (ANGPTL4) pathways may be a new pharmacologic target for treatment of obesity. The present study was conducted to test the effect of phillyrin, a glucoside, on obesity in mice. METHOD: Fifty mice were randomly divided into 5 groups (n=10): control group (C57BL/6J mice), obese mice group, two groups of obese mice treated with phillyrin (15 or 45mg/kg/day), one group of obese mice treated with PPAR/ agonist GW0742 (3mg/kg/day). Twelve weeks after treatment, body weight, liver weight, fat weight, lipid levels in the liver, serum levels of tumour necrosis factor-(TNF-), leptin, and insulin, expression of PPAR/, ANGPTL4, and AMP-activated protein kinase (AMPK) were determined. RESULTS: Treatment with phillyrin (15 or 45mg/kg) significantly decreased body weight, liver weight, fat weight, hepatic total cholesterol, free fatty acid, and triglyceride concentrations, serum levels of TNF-, leptin, and insulin concomitantly with up-regulated expression of PPAR/, ANGPTL4, and p-AMPK-. In addition, GW0742 has similar effect of phillyrin. CONCLUSIONS: The present results suggest that phillyrin could regulate the PPAR/-ANGPTL 4 pathway to lower body weight in obese C57BL/6J mice.


Assuntos
Angiopoietinas/biossíntese , Glucosídeos/farmacologia , Obesidade/tratamento farmacológico , PPAR alfa/biossíntese , Transdução de Sinais/efeitos dos fármacos , Angiopoietinas/genética , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , PPAR alfa/genética
16.
Pharmacol Rep ; 70(3): 439-445, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29627690

RESUMO

BACKGROUND: Mastitis is inflammation of a breast (or udder). Angiopoietin-like protein 2 (ANGPTL2) has been found as a key inflammatory mediator in mastitis. Purpose of this research was to investigate the mechanisms about repressing effect of kaempferol on mastitis. METHODS: Forty mice were randomly divided into 4 groups (n=10): C57BL/6J control mice, untreated murine mastitis, 10mg/kg kaempferol treated murine mastitis (ip), and 30mg/kg kaempferol treated murine mastitis (ip). Primary cultured mouse mammary epithelial cells (MMEC) were indiscriminately divided into seven groups including control group, 10mmol/L vehicle of kaempferol group, 10µmol/L kaempferol treated group, 20µg/mL LPS treated group, 1µmol/L kaempferol plus LPS treated group, 3µmol/L kaempferol plus LPS treated group, and 10µmol/L kaempferol plus LPS treated group. RESULTS: In murine mastitis, kaempferol (10 or 30mg/kg) treatment prevented mastitis development, decreased myeloperoxidase (MPO) production, interleukin (IL)-6 level, tumour necrosis factor-α (TNF-α) concentration, and ANGPTL2 expression. In MMEC, kaempferol (1, 3 or 10µM) reduced MPO production, TNF-α concentration, IL-6 level, and ANGPTL2 expression. CONCLUSIONS: The results in present study show that kaempferol modulates the expression of ANGPTL2 to lessen the mastitis in mice.


Assuntos
Proteínas Semelhantes a Angiopoietina/metabolismo , Quempferóis/farmacologia , Mastite/tratamento farmacológico , Mastite/metabolismo , Proteína 2 Semelhante a Angiopoietina , Animais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Life Sci ; 209: 97-102, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30048696

RESUMO

AIMS: Recent investigations have shown that dimethylarginine dimethylaminohydrolase (DDAH) may be related to sleep disorder. The present study was conducted to test the hypnotic effect of jujubosides from Semen Ziziphi Spinosae (SZSJ) on sleep deprivation and the mechanisms involved. MATERIALS AND METHODS: Forty rats were randomly divided into 4 groups (n = 10): two groups of sleep-deprived rats treated with SZSJ (10 or 30 mg/kg per day), sleep-deprived rats group, and control group. At the end of experiment, cerebral DDAH expression, cerebral asymmetric dimethylarginine (ADMA) level, sleep parameters, behavioral activities, and cerebral neurotransmitters level brain was examined. KEY FINDINGS: Six days after treatment, SZSJ treatment up-regulated cerebral expression of DDAH I and DDAH II concomitantly with elevated parameters of total sleep time, cerebral γ­aminobutyric acid and 5­hydroxytryptamine, and reduced values of forelimb lifting-up frequency and walking time, cerebral 8-isoprostane, ADMA, noradrenaline, and glutamic acid in sleep deprivation of rats. SIGNIFICANCE: The present results suggest that SZSJ Protects against insomnia by a decrease in ADMA level and an improvement in DDAH production in sleep-deprived rats.


Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Hipnóticos e Sedativos/farmacologia , Substâncias Protetoras/farmacologia , Privação do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Ziziphus/química , Animais , Arginina/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Privação do Sono/metabolismo
18.
Eur J Pharmacol ; 836: 122-128, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30096295

RESUMO

N-acetylgalactosaminyltransferase 2-Angiopoietin-like protein 3-lipoprotein lipase (GALNT2-ANGPTL3-LPL) pathway may be a useful pharmacologic objective for dyslipidemia. The present study was conducted to test the effect of paeoniflorin, a monoterpene Glycoside, on dyslipidemia in mice. Fifty mice were randomly divided into five groups (n = 10): three groups of apolipoprotein E-null (ApoE-/-) mice treated with paeoniflorin (10 or 20 or 30 mg/kg/day), untreated ApoE-/- mice group, and C57BL/6J control group. Six weeks after treatment, expression of hepatic ANGPTL3, hepatic GALNT2 and adipose tissue LPL, lipid levels in the liver and blood were quantified. Treatment with paeoniflorin (10 or 20 or 30 mg/kg) obviously down-regulated expression of ANGPTL3 and up-regulated expressions of GALNT2 and LPL concomitantly with elevated plasma high-density lipoprotein cholesterol level, reduced plasma concentrations of low-density lipoprotein cholesterol, total cholesterol, triglyceride, malonaldehyde, and 8-isoprostane. The present results suggest that paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice.


Assuntos
Proteínas Semelhantes a Angiopoietina/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Glucosídeos/farmacologia , Lipase Lipoproteica/metabolismo , Monoterpenos/farmacologia , N-Acetilgalactosaminiltransferases/metabolismo , Proteína 3 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/genética , Animais , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Dislipidemias/genética , Dislipidemias/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucosídeos/uso terapêutico , Lipase Lipoproteica/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/sangue , Camundongos , Monoterpenos/uso terapêutico , N-Acetilgalactosaminiltransferases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Polipeptídeo N-Acetilgalactosaminiltransferase
19.
J Agric Food Chem ; 66(34): 8983-8990, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30092639

RESUMO

Previous investigations have shown molecular cross-talk among activated adenosine monophosphate-activated protein kinase (AMPK), proprotein convertase subtilisin/kexin type 9 (PCSK9), sterol regulatory element-binding proteins (SREBPs), and low-density lipoprotein receptor (LDLR) and that it may be an innovative pharmacologic objective for treating obesity. We scrutinized the beneficial effect of naringin, a flavanone-7- O-glycoside, on obesity and the mechanisms in the present study. We arbitrarily divided 50 mice into five groups ( n = 10): 25 or 50 or 100 mg/kg/day naringin-treated obese mice (gavage for 8 weeks), untreated obese mice, and C57BL/6J control. After 8 weeks, body weight was 51.8 ± 4.4 in the untreated obese mice group, while the weights were 41.4 ± 4.1, 34.6 ± 2.2, and 28.0 ± 2.3 in 25, 50,100 mg/kg naringin groups, respectively. Moreover, naringin treatment significantly decreased plasma 8-isoprostane (an indicator of the oxidative stress) level, fat weight, liver weight, hepatic total cholesterol concentration, hepatic triglyceride concentration, plasma leptin level, plasma insulin content, plasma low-density lipoprotein cholesterol level, and plasma PCSK9 production concomitantly with down-regulated expression of SREBP-2, PCSK9, and SREBP-1, and up-regulated expression of p-AMPKα and LDLR. The present results suggest that naringin activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR to reduce the body weight of obese C57BL/6J mice.


Assuntos
Flavanonas/administração & dosagem , Obesidade/tratamento farmacológico , Pró-Proteína Convertase 9/genética , Proteínas Quinases/metabolismo , Receptores de LDL/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Quinases Proteína-Quinases Ativadas por AMP , Animais , Peso Corporal/efeitos dos fármacos , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Pró-Proteína Convertase 9/metabolismo , Proteínas Quinases/genética , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
20.
Inflammation ; 41(1): 299-306, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29119338

RESUMO

Chronic endometritis is a continuous inflammation of uterine endometrium. Recent research has shown that higher asymmetric dimethylarginine (ADMA) levels contribute to endothelial dysfunction. In the present study, we tested whether there is a correlation between endometritis and ADMA in LPS-induced endometritis rat and the mechanisms involved. Thirty-six rats were divided into two groups: blank control group and rat model of endometritis group. The entire infused uterus were removed to observe the changes of histopathology, production of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, 8-isoprostane, and reactive oxygen species (ROS), and gene expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), protein-methyl transferase 1 (PRMT1), TNF-α, and IL-6. In endometritis rat group, characteristic histopathologic changes in uteri were observed. The uterine 8-isoprostane, ROS, MPO activity, IL-6 and TNF-α concentrations, PRMT1, IL-6, and TNF-α expressions were significantly elevated, and DDAH2 expression was notably reduced in endometritis group compared with control group. The present findings suggest that elevated levels of ADMA are associated with lower DDAH2 and higher PRMT1 in LPS-induced endometritis rat.


Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Endometriose/enzimologia , Lipopolissacarídeos , Proteína-Arginina N-Metiltransferases/metabolismo , Útero/enzimologia , Amidoidrolases/genética , Animais , Arginina/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Endometriose/induzido quimicamente , Endometriose/genética , Endometriose/patologia , Feminino , Interleucina-6/genética , Interleucina-6/metabolismo , Peroxidase/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Útero/patologia
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