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1.
Korean J Intern Med ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32942841

RESUMO

Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

2.
Acta Pharmacol Sin ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555441

RESUMO

Reducing immunosuppressant-related complications using conventional drugs is an efficient therapeutic strategy. L-carnitine (LC) has been shown to protect against various types of renal injury. In this study, we investigated the renoprotective effects of LC in a rat model of chronic tacrolimus (TAC) nephropathy. SD rats were injected with TAC (1.5 mg · kg-1 · d-1, sc) for 4 weeks. Renoprotective effects of LC were assessed in terms of renal function, histopathology, oxidative stress, expression of inflammatory and fibrotic cytokines, programmed cell death (pyroptosis, apoptosis, and autophagy), mitochondrial function, and PI3K/AKT/PTEN signaling. Chronic TAC nephropathy was characterized by severe renal dysfunction and typical histological features of chronic nephropathy. At a molecular level, TAC markedly increased the expression of inflammatory and fibrotic cytokines in the kidney, induced oxidative stress, and led to mitochondrial dysfunction and programmed cell death through activation of PI3K/AKT and inhibition of PTEN. Coadministration of LC (200 mg · kg-1 · d-1, ip) caused a prominent improvement in renal function and ameliorated histological changes of kidneys in TAC-treated rats. Furthermore, LC exerted anti-inflammatory and antioxidant effects, prevented mitochondrial dysfunction, and modulated the expression of a series of apoptosis- and autophagy-controlling genes to promote cell survival. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TAC (50 µg/mL) in vitro, which induced production of intracellular reactive oxygen species and expression of an array of genes controlling programmed cell death (pyroptosis, apoptosis, and autophagy) through interfering with PI3K/AKT/PTEN signaling. The harmful responses of HK-2 cells to TAC were significantly attenuated by cotreatment with LC and the PI3K inhibitor LY294002 (25 µM). In conclusion, LC treatment protects against chronic TAC nephropathy through interfering the PI3K/AKT/PTEN signaling.

3.
Acta Pharmacol Sin ; 41(12): 1597-1608, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32300244

RESUMO

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and H2O2-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.2 U/g per day, ip) was administered for 7 or 14 days. After the treatment, rats were euthanized; the obstructed kidneys were harvested for further examination. We found that PK administration significantly attenuated interstitial inflammation and fibrosis, and downregulated the expression of proinflammatory (MCP-1, TLR-2, and OPN) and profibrotic (TGF-ß1 and CTGF) cytokines in obstructed kidney. UUO-induced oxidative stress, closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling, which were abolished by PK administration. We further showed that PK administration increased the expression of bradykinin receptors 1 and 2 (B1R and B2R) mRNA and the production of NO and cAMP in kidney tissues. Coadministration with either B1R antagonist (des-Arg9-[Leu8]-bradykinin) or B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney. In H2O2-treated HK-2 cells, addition of PK (6 pg/mL) significantly decreased ROS production, regulated the expression of oxidant and antioxidant enzymes, suppressed the expression of TGF-ß1 and MCP-1, and inhibited cell apoptosis. Our data demonstrate that PK treatment protects against the progression of renal fibrosis in obstructed kidneys.

4.
Int J Mol Sci ; 17(12)2016 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-27916794

RESUMO

Flammulina velutipes, one of the most popular mushroom species in the world, has been recognized as a useful model system to study the biochemical and physiological aspects of the formation and elongation of fruit body. However, few reports have been published on the regulation of fruiting body formation in F. velutipes at the molecular level. In this study, a jacalin-related lectin gene from F. velutipes was characterized. The phylogenetic tree revealed that Fv-JRL1 clustered with other basidiomycete jacalin-like lectins. Moreover, the transcriptional pattern of the Fv-JRL1 gene in different developmental stages of F. velutipes implied that Fv-JRL1 could be important for formation of fruit body. Additionally, RNA interference (RNAi) and overexpression analyses provided powerful evidence that the lectin gene Fv-JRL1 from F. velutipes plays important roles in fruiting body formation.


Assuntos
Flammulina/crescimento & desenvolvimento , Flammulina/metabolismo , Carpóforos/crescimento & desenvolvimento , Carpóforos/metabolismo , Lectinas/metabolismo , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Lectinas de Plantas/metabolismo , Flammulina/genética , Carpóforos/genética , Lectinas/química , Micélio/genética , Lectinas de Plantas/química
5.
Int J Syst Evol Microbiol ; 66(12): 5028-5033, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27582375

RESUMO

A novel actinomycete strain, designated Js-1T, was isolated from Tremella fuciformis collected from Gutian, Fujian Province, in southeastern China. The taxonomic status of this strain was determined by a polyphasic approach, which demonstrated that the novel strain was a member of the genus Streptomyces. The cell walls of this strain were found to contain ll-diaminopimelic acid, muramic acid and glycine. An analysis of whole-cell hydrolysates revealed that no characteristic sugar was present. The key identified menaquinones were MK-9 (H6) and MK-9 (H8), while the diagnostic polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylmethylethanolamine and phosphatidylglycerol. The main cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0, C16 : 0 and iso-C16 : 0. An analysis of an almost complete 16S rRNA gene sequence showed that the strain shared the highest levels of sequence similarity with Streptomyces sannanensisKC-7038T (97.87 %), Streptomyces hebeiensis YIM 001T (97.84 %), Streptomyces pathocidini NBRC 13812T (97.80 %), Streptomyces cocklensis BK168T (97.25 %), Streptomyces coerulescens NBRC 12758T (97.12 %), Streptomyces aurantiogriseus NBRC 12842T (97.06 %) and Streptomyces rimosussubsp. rimosus ATCC 10970T (97.04 %). The DNA G+C content of the genomic DNA of strain Js-1T was 70.1 mol%. Furthermore, DNA-DNA hybridization tests revealed that the relatedness values between strain Js-1T and the most closely related species ranged from 15.10 to 47.20 %. Based on its phenotypic and genotypic characteristics, strain Js-1T (=CCTCC M 2011365T=JCM 30846T) is considered to represent a novel species within the genus Streptomyces, which we classified as Streptomycestremellae sp. nov.


Assuntos
Agaricales , Basidiomycota , Filogenia , Streptomyces/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo , Streptomyces/genética , Streptomyces/isolamento & purificação , Vitamina K 2/análogos & derivados , Vitamina K 2/química
6.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(10): 1244-8, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26677678

RESUMO

OBJECTIVE: To study the effect of Buyang Huanwu Decoction (BHD), Xuefu Zhuyu Decoction (XZD), and Sijunzi Decoction (SD) contained serums on expressions of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signals, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and to explore possible anti-atherosclerotic mechanisms. METHODS: Twenty New Zealand rabbits were divided into 4 groups at random, i.e., the normal control group, the BHD group (6.7 g/kg), the XZD group (3.6 g/kg), and the SD group (1.6 g/kg), 5 in each group. All medication lasted for 7 successive days. Two h after the final medication, about 50 mL blood was withdrawn from rabbit heart for preparing serums. Human umbilical vein endothelial cell ECV304 were cultured in vitro for 18 h and randomly divided into the blank control group, the model group, the Western medicine (WM) control group, the BHD group, the XZD group, and the SD group at random. ECV304, except in the blank control group, were stimulated with lipopolysaccharide (LPS) for 2 h. Those in the WM control group and CM groups were treated respectively with corresponding CM contained serum for 24 h. Finally gene and protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor-6 (TRAF-6), NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 were detected by fluorescent quantitative PCR and Western blot. RESULTS: Compared with the blank control group, mRNA expressions of TLR4, MyD88, TRAF-6, NF-KB, LOX-1 , TNF-cx, ICAM-1, and VCAM-1 increased significantly; protein expressions of TLR4, NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 also increased significantly in the model group (P < 0.01). Compared with the model group, mRNA and protein expressions of each index could be significantly inhibited in the BHD group, the XZD group, and the WM control group (P < 0.05). Besides, mRNA and protein expressions of each index could be significantly elevated more in the BHD group and the XZD group than in the WM control group (P < 0.05). No statistical difference existed in each index between the SD group and the rest groups (P > 0.05). CONCLUSIONS: The mechanism of BHD and XZD for fighting against atherosclerosis might be associated with inhibiting TLR4/NF-κB signal transduction pathway and expressions of its downstream inflammatory factors such as LOX-1, TNF-α, ICAM-1, and VCAM-1. But SD showed no associated effect on atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Coelhos , Receptores Depuradores Classe E , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Veias Umbilicais , Molécula 1 de Adesão de Célula Vascular/metabolismo
7.
Nephron Exp Nephrol ; 126(3): 148-56, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24855017

RESUMO

BACKGROUND: Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. METHODS: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. RESULTS: Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-ß1 and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. CONCLUSIONS: LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.


Assuntos
Benzazepinas/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Isoxazóis/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antifibrinolíticos/administração & dosagem , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Sinergismo Farmacológico , Leflunomida , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento
8.
Genome ; 55(9): 667-72, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22937907

RESUMO

The mitochondrial intermediate peptidase (MIP) gene is conserved in fungi. It is linked closely with the mating-type A (mtA) gene. In this study, a fragment of the MIP gene in Volvariella volvacea (Bull. ex Fr.) Singer was first cloned by homologue-based cloning technology. Subsequently, the entire MIP DNA sequence (PYd21-MIP) was obtained after the fragment was compared with the genomic data through BLAST analysis. The PYd21-MIP sequence appeared to be homologous with the MIP gene in other fungi. Phylogenetic analysis of PYd21-MIP and other MIP sequences from diverse fungi agreed with the current organism phylogeny. Analysis of protein domains by InterProScan software and motif searching demonstrated that PYd21-MIP encodes a homologous MIP protein. These data support the hypothesis that the PYd21-MIP protein is a Hog-MIP protein homologue from V. volvacea.


Assuntos
Proteínas Fúngicas/genética , Genes Fúngicos Tipo Acasalamento , Metaloendopeptidases/genética , Volvariella/genética , China , Clonagem Molecular , DNA Fúngico/genética , Filogenia , Alinhamento de Sequência , Análise de Sequência de DNA , Volvariella/química
9.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(2): 219-23, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22574597

RESUMO

OBJECTIVE: To investigate the effects of Yiqi Huoxue Compound (YHC) contained drug serum on the expressions of TLR4 and its downstream signal transduction pathway and LOX-1, TNF-alpha, ICAM-1 in human umbilical vein endothelial cells (HUVECs), and to study its possible anti-atherosclerosis (AS) mechanism. METHODS Twenty New Zealand rabbits were divided into 4 groups in random, i. e., the normal control group, the high concentration group, the middle concentration group, and the low concentration group, 5 in each group. Normal saline was given to rabbits in the normal control group by gastrogavage. High, middle, and low concentration of YHC was respectively given to rabbits in the rest 3 groups by gastrogavage for 7 successive days. The blood was withdrawn from the heart 2 h after the last gastrogavage. The serum was isolated after centrifuge. HUVECs was in vitro cultured and then randomly divided into 6 groups, i. e., the normal control group, the model group, the Western medicine control group, the high, middle, and low YHC groups. HUVECs were stimulated with LPS for 2 h, and then treated with high, middle, and low YHC contained serum. HUVECs were collected 24 h later. The gene expressions of TLR4, MyD88, TRAF-6, TRAM, TRIF, NF-kappaB, LOX-1, TNF-alpha, and ICAM-1 were detected using fluorescent quantitative PCR. The protein expressions of TLR4, MyD88, TRAF-6, and LOX-1 were determined using Western blot method. RESULTS: After HUVECs were stimulated by LPS, the expressions of TLR4, MyD88, TRAF-6, TRAM, TRIF, NF-kappaB, LOX-1, TNF-alpha, and ICAM-1 were enhanced, showing statistical difference when compared with the vehicle control group (P < 0.01). YHC contained serum significantly decreased the higher expressions of TLR4, MyD88, TRAF-6, NF-kappaB, LOX-1, TNF-alpha, and ICAM-1, showing statistical difference when compared with the model group (P < 0.05). CONCLUSIONS: YHC could inhibit the TLR signal transduction pathway and the expressions of LOX-1, TNF-alpha, and ICAM-1. These might be one of the mechanisms for treating various immune inflammatory diseases and preventing AS.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , NF-kappa B/metabolismo , Coelhos , Receptores Depuradores Classe E/metabolismo , Soro , Fator de Necrose Tumoral alfa/metabolismo
10.
Wei Sheng Wu Xue Bao ; 46(3): 463-6, 2006 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-16933622

RESUMO

Organophosphate pesticides are used widely all over the world and play an important role in plant pest control. However these pesticides are considered as pollutants and harmful to human health. To search for microorganisms that can degrade organophosphate pesticides with high efficiency, a bacterial strain, coded as JS018, was isolated and screened from the soil in the vicinity of Shanming Pesticides Factory, Shanming, Fujian. Laboratory tests showed that the bacterium could degrade several kinds of organophosphate pesticides, such as Parathion-methyl and phoxin. The strain's degrading rates on phoxin, Parathion-methyl, hostathion and dichlorvos in LB liquid fermentation medium for 36 h were 99%, 96%, 80.4% and 69.0% respectively. The bacterial colonies on LB plate appeared shiny and pale-pink in color. The bacteria were Gram-negative coccoids, 0.5 - 0.7 microm in diameter. They grew well at 30 - 38 degrees C and pH 7.0 - 9.0. The optimal temperature and pH for cell growth was 32 degrees C and pH 7.5 - 8.0, respectively. They did not grow in medium containing 6% or more NaCl. The antibiotic susceptibility tests showed that the strain was resistant to ampicillin, penicillin and lincomycin. It was sensitive to kanamycin, tetracycline and gentamicin. Laboratory tests also showed that the strain could ferment D-glucose, trehalose, melezitose and ethanol. It was negative in the production of indole and hydrogen sulfide. It could not liquefy gelatin, utilize citrate, nor ferment L-arabinose, sucrose, D-mannitol, D-xylose, fructose, D-galactose, maltose or lactose. The catalase, urease and nitrate reduction were positive. Based on its morphological, physiological and biochemical properties as well as the 16S rDNA sequence analysis result, the strain was tentatively identified as Roseomonas sp.


Assuntos
Poluentes Ambientais/metabolismo , Methylobacteriaceae/isolamento & purificação , Methylobacteriaceae/metabolismo , Organofosfatos/metabolismo , Praguicidas/metabolismo , Biodegradação Ambiental , DNA Ribossômico/análise , DNA Ribossômico/genética , Poluentes Ambientais/isolamento & purificação , Methylobacteriaceae/genética , Methylobacteriaceae/ultraestrutura , Microscopia Eletrônica , Organofosfatos/isolamento & purificação , Praguicidas/isolamento & purificação , Filogenia , Análise de Sequência de DNA , Microbiologia do Solo
11.
Artigo em Chinês | MEDLINE | ID: mdl-15108528

RESUMO

OBJECTIVE: To study the impact of environmental temperature on the development of Schistosoma japonicum larvae within the Oncomelania hupensis. METHODS: Oncomelania snails, collected from the field and free of S. japonicum infection, were exposed to miracidiae of S. japonicum in a ratio of 1:20 and raised at 30 degrees C, 27 degrees C, 24 degrees C, 21 degrees C and 18 degrees C, respectively. The prepatent period of larvae within the Oncomelania hupensis and the developmental velocity were determined, of which the relationship with the temperature was analysed. RESULTS: The average prepatent period of cercariae in snail was (128.89 +/- 16.05) d, (95.00 +/- 21.03) d, (71.93 +/- 12.74) d and (62.74 +/- 14.19) d at 21 degrees C, 24 degrees C, 27 degrees C, 30 degrees C, respectively. The regression formulation between prepatent period and temperature was y = 730.68x(-0.8918) (r = 0.9976, P < 0.01). And the regression formulation between developmental velocity of S. japonicum larvae in snail and temperature was y = 0.0235ln(x) -0.0639 (r = 0.9973, P < 0.01). It was derived that the unitial temperature for the development of S. japonicum within the snails was 15.17 degrees C +/- 0.43 degree C. CONCLUSION: The development of S. japonicum larvae within the Oncomelania snails declines with the decrease of temperature.


Assuntos
Schistosoma japonicum/crescimento & desenvolvimento , Caramujos/parasitologia , Temperatura , Animais , Interações Hospedeiro-Parasita , Larva/crescimento & desenvolvimento
12.
Artigo em Chinês | MEDLINE | ID: mdl-12567571

RESUMO

OBJECTIVE: To understand the variation in response of Oncomelania hupensis to niclosamide. METHODS: Snails were collected from 37 sampling areas distributed in 10 provinces (municipalities) using random environmental sampling methods in accordance with the different types and categories of snail habitats. In laboratory the snails were immersed in solutions of niclosamide for 24 and 48 hours at 25 degrees C. RESULTS: 1.0 mg/L niclosamide showed 100% killing effect on snails in 24 hours. The LC50 concentrations for snails immersed for 24 hours ranged from 0.0320 to 0.1689 mg/L with a mean value of 0.0920 mg/L. 0.5 mg/L niclosamide showed 100% killing effect on snails in 48 hours. The LC50 values for snails immersed for 48 hours ranged between 0.0299 and 0.1114 mg/L with a mean of 0.0627 mg/L. There is a significant difference in snail sensitivity to niclosamide between sampling areas. CONCLUSION: The sensitivity to niclosamide varied in snails from different sampling fields, but the chemical in a concentration of 1.0 mg/L showed 100% effect of killing snails, which is consistent to the manual of schistosomiasis control.


Assuntos
Moluscocidas/farmacologia , Niclosamida/farmacologia , Caramujos/efeitos dos fármacos , Animais , China , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Dose Letal Mediana , Amostragem
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