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1.
Acta Pharmacol Sin ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32203087

RESUMO

Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in PINP. Because the nuclear factor erythroid-2-related factor 2 (Nrf2) has been considered as the critical regulator of endogenous antioxidant defense, we here explored whether activation of Nrf2 could attenuate PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to assess mechanical allodynia. We showed that a single dose of Nrf2 activator, oltipraz (10, 50, and 100 mg/kg), dose-dependently attenuated established mechanical allodynia, whereas repeated injection of oltipraz (100 mg· kg-1· d-1, i.p. from d 14 to d 18) almost abolished the mechanical allodynia in PINP rats. The antinociceptive effect of oltipraz was blocked by pre-injection of Nrf2 inhibitor trigonelline (20 mg/kg, i.p.). Early treatment with oltipraz (100 mg· kg-1· d-1, i.p. from d 0 to d 6) failed to prevent the development of the PINP, but delayed its onset. Western blot and immunofluorescence analysis revealed that the expression levels of Nrf2 and HO-1 were significantly upregulated in the spinal cord of PINP rats. Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats, which was reversed by pre-injection of trigonelline. These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord.

2.
Medicine (Baltimore) ; 98(44): e17867, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31689880

RESUMO

AIMS: Interleukin(IL)-22 plays an important role in promoting liver regeneration and repair, but its role in chronic HBV-related liver diseasesis not clear. The goal of this study was to evaluate associations between eight IL22 single nucleotide polymorphisms (SNPs) and the development of chronic HBV cirrhosis and HBV-related HCC within a Chinese Han population. METHODS: We investigated associations between single nucleotide polymorphisms (SNPs) in the IL22 gene (rs1026788, rs2227472, rs2227491, rs2227485, rs1179249, rs2046068,rs2227473, and rs7314777) and the risk of HBV-related chronic liver diseases within a Han population in Northeast China. A total of 649 participants were included in the study, including 103 patients with CHB, 264 patients with LC, and 282 patients with HCC. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using chi-square test. Haplotype analysis was conducted by haploview software. RESULTS: Genotype and allele distributions of SNPs rs1179249 and rs2227472 differed between LC and CHB groups (both P < 0.05).The G alleles of SNP rs2227491 and rs1026788 were more frequent in the LC group than in the CHB group (P = 0.046, P = 0.041 respectively). A IL22 haplotype consisting of the minor alleles of SNP rs1179249 and the major alleles of seven other SNPs occurred less frequently in the LC and HCC groups than in the CHB group (28.2%, 33.94%, and 37.86%, respectively, P < 0.05). Moreover, there were no significant associations between smoking or drinking and IL22 SNPs on the risk of HCC (P > 0.05). CONCLUSION: IL22 genetic variations were associated with chronic HBV infection progression, especially in the HBV-LC group. The IL22 genetic variations may help clinicians initiate the correct treatment strategy at the CHB stage.


Assuntos
Carcinoma Hepatocelular/virologia , Hepatite B Crônica/genética , Interleucinas/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Estudos Retrospectivos , Fumar/efeitos adversos
3.
Biomed Pharmacother ; 120: 109504, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31627091

RESUMO

Treating Cancer-induced bone pain (CIBP) continues to be a major clinical challenge and underlying mechanisms of CIBP remain unclear. Recently, emerging body of evidence suggested the endocannabinoid system (ECS) may play essential roles in CIBP. Here, we summarized the current understanding of the antinociceptive mechanisms of endocannabinoids in CIBP and discussed the beneficial effects of endocannabinoid for CIBP treatment. Targeting non-selective cannabinoid 1 receptors or selective cannabinoid 2 receptors, and modulation of peripheral AEA and 2-AG, as well as the inhibition the function of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have produced analgesic effects in animal models of CIBP. Management of ECS therefore appears to be a promising way for the treatment of CIBP in terms of efficacy and safety. Further clinical studies are encouraged to confirm the possible translation to humans of the very promising results already obtained in the preclinical studies.

4.
World J Gastroenterol ; 25(32): 4696-4714, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31528095

RESUMO

BACKGROUND: About one-third of refractory irritable bowel syndrome (IBS) cases are caused by gastrointestinal (GI) infection/inflammation, known as post-infectious/post-inflammatory IBS (PI-IBS). Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS, whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear. AIM: To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS. METHODS: Sprague-Dawley rats were divided into a normal control group, a model control group, a mild moxibustion group, and a sham mild moxibustion group. PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu (ST 25) and Zusanli (ST36) for 7 consecutive days for 10 min each time. The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited. Abdominal withdrawal reflex (AWR) score was measured to assess the visceral sensitivity, and colon histopathology and ultrastructure, colonic myeloperoxidase (MPO) activity, and serum C-reactive protein (CRP) level were measured to evaluate low-grade colonic inflammation in rats. The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence, qRT-PCR, and Western blot. RESULTS: The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group. Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats. Additionally, mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1ß, IL-18, and resistance-like molecule ß by promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD (ASC) and cysteinyl-aspartate-specific proteinase 1 (Caspase-1). The relative DNA abundances of Lactobacillus, Bifidobacteria, Faecalibacterium prausnitzii, and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6, ASC, and Caspase-1 in the colon. CONCLUSION: These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling.


Assuntos
Microbioma Gastrointestinal/imunologia , Inflamação/terapia , Síndrome do Intestino Irritável/terapia , Moxibustão/métodos , Transdução de Sinais/imunologia , Animais , Modelos Animais de Doenças , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/complicações , Inflamação/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Síndrome do Intestino Irritável/imunologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Angiotensina/imunologia , Receptores de Angiotensina/metabolismo , Receptores de Vasopressinas/imunologia , Receptores de Vasopressinas/metabolismo , Organismos Livres de Patógenos Específicos , Ácido Trinitrobenzenossulfônico/administração & dosagem , Ácido Trinitrobenzenossulfônico/imunologia
5.
Pharmacol Res ; 148: 104385, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400402

RESUMO

Ischemia-reperfusion (I/R) injury is accompanied with high morbidity and mortality and has seriously negative social and economic influences. Unfortunately, few effective therapeutic strategies are available to improve its outcome. Berberine is a natural medicine possessing multiple beneficial biological activities. Emerging evidence indicates that berberine has potential protective effects against I/R injury in brain, heart, kidney, liver, intestine and testis. However, up-to-date review focusing on the beneficial role of berberine against I/R injury is not yet available. In this paper, results from animal models and clinical studies are concisely presented and its mechanisms are discussed. We found that berberine ameliorates I/R injury in animal models via its anti-oxidant, anti-apoptotic and anti-inflammatory effects. Moreover, berberine also attenuates I/R injury by suppressing endoplasmic reticulum stress and promoting autophagy. Additionally, regulation of periphery immune system may also contributes to the beneficial effect of berberine against I/R injury. Although clinical evidence is limited, the current studies indicate that berberine may attenuate I/R injury via inhibiting excessive inflammatory response in patients. Collectively, berberine might be used as an alternative therapeutic strategy for the management of I/R injury.

6.
J Agric Food Chem ; 67(30): 8348-8360, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31304751

RESUMO

We have recently demonstrated that tau hyperphosphorylation causes diabetic synaptic neurodegeneration of retinal ganglion cells (RGCs), which might be the earliest affair during the pathogenesis of diabetic retinopathy (DR). Thus, there is a pressing need to seek therapeutic agents possessing neuroprotective effects against tau hyperphosphorylation in RGCs for arresting the progression of DR. Here, using a well-characterized diabetes model of db/db mouse, we discovered that topical ocular application of 10 mg/kg/day of ginsenoside Rg1 (GRg1), one of the major active ingredients extracted from Panax ginseng and Panax notoginseng, ameliorated hyperphosphorylated tau-triggered RGCs synaptic neurodegeneration in diabetic mice. The neuroprotective effects of GRg1 on diabetic retinae were abrogated when retinal IRS-1 or Akt was suppressed by intravitreal injection with si-IRS-1 or topically coadministered with a specific inhibitor of Akt, respectively. However, selective repression of retinal GSK3ß by intravitreal administration of si-GSK3ß rescued the neuroprotective properties of GRg1 when Akt was inactivated. Therefore, the present study showed for the first time that GRg1 can prevent hyperphosphorylated tau-induced synaptic neurodegeneration of RGCs via activation of IRS-1/Akt/GSK3ß signaling in the early phase of DR. Moreover, our data clarify the potential therapeutic significance of GRg1 for neuroprotective intervention strategies of DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Ginsenosídeos/administração & dosagem , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Proteínas tau/metabolismo , Animais , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/tratamento farmacológico , Degeneração Neural/genética , Degeneração Neural/metabolismo , Panax notoginseng/química , Fosforilação , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/genética , Retina/patologia , Células Ganglionares da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas tau/genética
7.
Pharmacol Res ; 147: 104339, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31276771

RESUMO

Cancer-induced bone pain (CIBP) remains a major challenge in patients suffering from bone metastases because of the complex mechanisms and unsatisfactory treatments. Emerging evidence have shown that activation of inflammasomes contribute to the development of inflammatory and neuropathic pain. However, the role of spinal inflammasomes in CIBP remains unclear. In the present study, we explored the specific cellular mechanisms of NLRP3 inflammasome in the process of CIBP in rats. MCC950 is a small molecule inhibitor of the NLRP3 inflammasome that exhibits remarkable activity in inflammatory diseases. Our behavioral results confirmed that both single and persistent treatment with MCC950 markedly attenuated CIBP-related mechanical allodynia. The expression of NLRP3 inflammasome, including NLRP3, ASC, Caspase-1, were significantly increased in a time-dependent manner. Furthermore, spinal IL-1ß, cleaved by cysteine-aspartic acid protease, was upregulated in this study. Chronic administration with MCC950 restored the protein expression of NLRP3 inflammasome and significantly suppressed the upregulation of IL-1ß. Spinal NLRP3 inflammasome might be a novel therapeutic target for treatment of CIBP.

8.
Vet Immunol Immunopathol ; 212: 15-22, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31213247

RESUMO

Marek's disease virus (MDV), an α-herpesvirus targeting avian species, causes fatal Marek's disease (MD) in chickens. The host interferon (IFN) responses play a key role in resisting viral infection. However, host IFN responses following MDV infection in the chicken central immune organs (thymus and bursa of Fabricius), which contain numerous MDV target cells, is poorly understood. In this study, we performed animal experiments in specific pathogen-free chickens infected with two virulent MDV strains (BS/15 and Md5) or without infection as negative controls. Specifically, the type I IFN (IFN-α and IFN-ß) transcriptional and proteomic expression levels at 7, 10, 14, 17, and 21 days post infection (dpi) were detected and analyzed. Our results indicated that the mRNA and protein expression levels of IFN-α and IFN-ß in the thymus and bursa of Fabricius were mainly downregulated in cytolytic infection (such as 10 dpi) and reactivation (such as 17 dpi) stages, but not the latent (such as 14 dpi) stage of MDV infection, which was determined by comprehensively analyzing the MDV viral load and immune organ damage caused by MDV infection. These data suggest that MDV could inhibit the expression of host type I IFNs, which may be involved in the MDV-induced host immunosuppression and contribute to the immune escape of MDV from host immunity. Furthermore, we found that the downregulated expression of the host type I IFNs induced by BS/15 and Md5 infection was significantly different, which we speculated may be related to the diverse virulence and pathogenicity of MDV strains. In conclusion, our study demonstrated that MDV mostly inhibited the expression of type I IFNs in infected hosts, which may be associated to its pathogenesis.


Assuntos
Interferon Tipo I/imunologia , Doença de Marek/imunologia , Doenças das Aves Domésticas/imunologia , Animais , Bolsa de Fabricius/imunologia , Galinhas , Expressão Gênica , Herpesvirus Galináceo 2 , Interferon Tipo I/genética , Interferon-alfa/genética , Interferon-alfa/imunologia , Interferon beta/genética , Interferon beta/imunologia , Doenças das Aves Domésticas/virologia , Proteômica , RNA Mensageiro/genética , Organismos Livres de Patógenos Específicos , Timo/imunologia , Carga Viral , Virulência
9.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 150-154, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250607

RESUMO

OBJECTIVE: To investigate the effects of aerobic exercise and glutamine (Gln) on anti-oxidative stress and inflammatory factors in type 2 diabetes mellitus (T2MD) rats. METHODS: Diabetic rat model was induced by streptozotocin (STZ). Fifty 6-week old male SD rats were randomly divided into 5 groups (n=10), including quiet control group (N), diabetes control group (D), diabetic aerobic exercise group (DE), diabetic glutamine group (DG) and diabetic aerobic exercise glutamine group (DEG). After 6 weeks, the related indicators of glucose and lipid metabolism, anti-oxidative stress and inflammatory factors in diabetic rats were detected, and the possible mechanism affecting inflammatory response were explored. RESULTS: Compared with group N, the levels of serum malondialdehyde(MDA), blood glucose, total cholesterol(TC), triglyceride(TG), insulin, leptin and tumor necrosis factor-α(TNF-α) in group D were increased significantly (P<0.01). Compared with group D, serum levels of MDA, blood glucose, TC, TG, insulin, leptin and TNF-α in three intervention groups were decreased significantly, while the levels of SOD, GSH-Px and adiponectin were increased, and the combined effect was more obvious (P<0.01). CONCLUSION: Both aerobic exercise and Gln can relieve the glucose and lipid metabolism and disturbance, oxidative stress injury and inflammation in diabetic rats.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Glutamina/farmacologia , Estresse Oxidativo , Condicionamento Físico Animal , Animais , Glicemia/análise , Diabetes Mellitus Experimental , Leptina/sangue , Metabolismo dos Lipídeos , Lipídeos/sangue , Masculino , Malondialdeído/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
11.
Nat Commun ; 10(1): 1507, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944315

RESUMO

Exhaustion of cytotoxic effector natural killer (NK) and CD8+ T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/OTg mice permissive for persistent HCV infection, that NK and CD8+ T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8+ T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8+ T cell functions to prevent persistent HCV infection.


Assuntos
Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Hepatite C Crônica/virologia , Hepatócitos/virologia , Antígenos de Histocompatibilidade Classe I/imunologia , Interferon gama/imunologia , Ativação Linfocitária/fisiologia , Proteínas de Membrana/imunologia , Camundongos , Distribuição Aleatória
12.
Ann Endocrinol (Paris) ; 80(2): 72-76, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825997

RESUMO

OBJECTIVE: To investigate the relations of circulating adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) with carotid artery elasticity in patients with impaired glucose regulation (IGR). METHODS: A total of 208 subjects were enrolled from January 2013 to March 2014. One hundred forty-eight were IGR patients, and 60 had normal glucose tolerance (NGT). Carotid intima-media thickness (IMT), carotid artery pressure-strain elasticity coefficient (Eρ), stiffness (ß), arterial compliance (AC), and pulse wave velocity (PWVß), as well as blood pressure, body mass index, blood glucose, blood lipids, insulin resistance index, VCAM-1, and ICAM-1 were measured and compared between IGR and NGT patients. RESULTS: Eρ, ß and PWVß were significantly higher in the IGR group than in the NGT group (P<0.05), but the IMT showed no significant difference (P>0.05). VCAM-1 and ICAM-1 were significantly higher in the IGR group than in the NGT group (P<0.05). VCAM-1 and ICAM-1 were positively correlated with Eρ, ß, and PWVß and negatively correlated with AC in IGR patients. CONCLUSIONS: Changes in carotid artery elasticity and endothelial dysfunction are found in patients with IGR. Early comprehensive intervention should be performed in such IGR populations.


Assuntos
Artérias Carótidas/fisiopatologia , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Rigidez Vascular/fisiologia , Adulto , Idoso , Glicemia/metabolismo , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Elasticidade/fisiologia , Feminino , Intolerância à Glucose/diagnóstico , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/fisiopatologia , Análise de Onda de Pulso , Ultrassonografia , Adulto Jovem
13.
Mol Med Rep ; 19(2): 967-973, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569122

RESUMO

Uncontrolled proliferation and defective apoptosis are two major factors responsible for maintaining the malignant properties of melanoma cells. Our previous study demonstrated that induced expression of four reprogramming factors remodeled the phenotype of B16­F10 mouse melanoma cells into melanoma stem cells. The present study was conducted to investigate the effect of the four Yamanaka reprogramming factors, namely Oct4, Sox2, Klf4 and c­Myc (OSKM), on the proliferation and apoptosis of melanoma cells, and to identify the responsible molecular signals. The results identified that expression of the four reprogramming factors was highly induced by doxycycline treatment in the stable melanoma cell clone that was transfected with a plasmid expressing these factors, driven by the Tet­On element. It was further confirmed that induced expression of these factors enhanced the proliferation and suppressed the apoptosis of the melanoma cells. In addition, induced OSKM expression increased cell proliferation, accelerated the progression of the cell cycle, and upregulated the mRNA expression levels of Janus kinase 2 (JAK2) and Cyclin­B1. Induced expression of these factors also decreased the apoptosis, as well as upregulated B­cell lymphoma 2 (BCL­2) and downregulated BCL­2­associated X (BAX) mRNA expression levels. Taken together, the results suggested that upregulated JAK2 and Cyclin­B1 may be responsible for the enhanced proliferation of melanoma cells, and that BCL­2 upregulation and BAX downregulation may account for the suppressed apoptosis of these cells.


Assuntos
Reprogramação Celular , Doxiciclina/farmacologia , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , Fator 3 de Transcrição de Octâmero/genética , Proteínas Proto-Oncogênicas c-myc/genética , Fatores de Transcrição SOXB1/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina B1/genética , Ciclina B1/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Fatores de Transcrição Kruppel-Like/agonistas , Fatores de Transcrição Kruppel-Like/metabolismo , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator 3 de Transcrição de Octâmero/agonistas , Fator 3 de Transcrição de Octâmero/metabolismo , Plasmídeos/química , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/agonistas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição SOXB1/agonistas , Fatores de Transcrição SOXB1/metabolismo , Transfecção , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
14.
World J Clin Cases ; 6(13): 600-610, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30430115

RESUMO

AIM: To investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases. METHODS: This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05. RESULTS: Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load (P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 (severe liver fibrosis) and 4 (cirrhosis). CONCLUSION: Iron metabolism disorders occur in patients with HBV-related liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

15.
Biochem Biophys Res Commun ; 505(1): 317-324, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30249396

RESUMO

Pathological cardiac hypertrophy is the main risk factor for heart diseases. The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation system involved in the development of cardiac hypertrophic remodeling. Ubiquitin-activating enzyme E1, a key component of the UPS, catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation via proteasome. However, the functional role of E1 (UBA1) in regulation of hypertrophic remodeling in angiotensin II (Ang II)-infused mice remains unknown. In this study, male wild-type mice were treated with UBA1 inhibitor PYR-41 at two doses of 5 and 10 mg and infused with Ang II (1000 ng/kg/min) for 14 days. Systolic blood pressure was detected by using tail-cuff system. Cardiac function was assessed by echocardiography. Hypertrophic remodeling was analyzed examined by histological examinations. The expressions of genes and proteins were detected by quantitative real-time PCR and immunoblotting analysis. After 14 days, Ang II infusion significantly increased UBA1 expression at both mRNA and protein levels in the hearts. Furthermore, Ang II-infused mice showed a significant increase in systolic blood pressure compensatory cardiac function, hypertrophy, interstitial fibrosis, inflammation and oxidative stress compared with saline-treated controls, whereas these effects were dose-dependently attenuated in PYR-41-treated mice. These beneficial actions were associated mainly with inhibition of PTEN degradation and multiple downstream mediators (AKT, ERK1/2, STAT3, TGF-ß/Smad2/3 and NF-kB(p65)). In conclusion, these results indicate that inhibition of UBA1 suppresses Ang II-induced hypertrophic remodeling, and suggest that administration of low dose PYR-41 may be a new potential therapeutic approach for treating hypertensive heart diseases.


Assuntos
Benzoatos/farmacologia , Cardiomegalia/prevenção & controle , Furanos/farmacologia , Pirazóis/farmacologia , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Remodelação Ventricular/efeitos dos fármacos , Angiotensina II , Animais , Benzoatos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/induzido quimicamente , Cardiomegalia/fisiopatologia , Fibrose , Furanos/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Masculino , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Pirazóis/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo
16.
Int J Antimicrob Agents ; 52(6): 747-753, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30149137

RESUMO

Staphylococcus argenteus is increasingly reported. Evaluating the impact of S. argenteus infection on patient outcomes for future therapeutic and infection control decision-making is imperative. A retrospective study was conducted to investigate the prevalence of S. argenteus bacteraemia at a Taiwanese medical centre between 2010-2012. Staphylococcus argenteus was identified based on absence of the crtM gene and multilocus sequence typing (MLST) analysis. Clinical characteristics between S. argenteus and Staphylococcus aureus bacteraemia were compared. The independent effect of S. argenteus on bacteraemia mortality was evaluated. A total of 47 S. argenteus isolates were re-identified from 394 S. aureus bacteraemia isolates. All S. argenteus isolates were susceptible to methicillin and multiple other antibiotics. Most of the S. argenteus isolates (36/47; 76.6%) were sequence type 2550 (ST2550). Comparing the 47 S. argenteus bacteraemia cases with 232 methicillin-susceptible S. aureus (MSSA) bacteraemia cases, S. argenteus bacteraemia patients had significantly higher percentages of polymicrobial infection, recent hospitalisation in the past 3 months, thrombocytopenia, lower respiratory tract infection and short-term mortality. Compared with MSSA bacteraemia, S. argenteus bacteraemia was independently associated with an increased risk of mortality [adjusted hazard ratio (aHR) = 1.845, 95% confidence interval (CI) 1.033-3.294] using multivariate Cox regression analysis. In a stratified analysis, S. argenteus bacteraemia was associated with a higher mortality risk than MSSA bacteraemia among patients with prior healthcare-associated exposure (aHR = 2.769, 95% CI 1.489-5.149). Although more susceptible to multiple antibiotics, S. argenteus bacteraemia cases were independently associated with higher mortality than MSSA bacteraemia cases.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/mortalidade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/patologia , Infecções Comunitárias Adquiridas/patologia , Feminino , Genótipo , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estudos Retrospectivos , Infecções Estafilocócicas/patologia , Staphylococcus/classificação , Staphylococcus/genética , Análise de Sobrevida , Taiwan/epidemiologia
17.
World J Gastroenterol ; 24(28): 3130-3144, 2018 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-30065559

RESUMO

AIM: To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis. METHODS: A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls (HC), ulcerative colitis model group (UC), UC with 7 d of moxibustion (UC-7), UC with 14 d of moxibustion (UC-14), UC with mesalazine gavage (UC-W), HC with 7 d of moxibustion (HC-7), HC with 14 d of moxibustion (HC-14). Moxibustion was applied to the bilateral Tianshu (ST25). Gut microbiome profiling was conducted by 16S rRNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS: Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term (7 d) but no longer term (14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12 (IL-12) (P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, IgA, tumour necrosis factor-α and its receptors 1 (TNFR1) and TNFR2 (P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10 (P < 0.01) and transforming growth factor-ß (P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion. CONCLUSION: Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity.


Assuntos
Bactérias/metabolismo , Colite Ulcerativa/terapia , Microbioma Gastrointestinal/fisiologia , Moxibustão , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/imunologia , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Citocinas/imunologia , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Proteobactérias , RNA Ribossômico 16S/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Fatores de Tempo , Resultado do Tratamento
18.
Nanoscale Res Lett ; 13(1): 250, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30136049

RESUMO

Hierarchical SnO2 blooming nanoflowers were successfully fabricated via a simple yet facile hydrothermal method with the help of different surfactants. Here we focus on exploring the promotion effects of surfactants on the self-assembly of 2D SnO2 nanosheets into 3D SnO2 flower-like structures as well as their gas-sensing performances. The polyporous flower-like SnO2 sensor exhibits excellent gas-sensing performances to ethanol and H2S gas due to high porosity when polyvinyl pyrrolidone is added into the precursor solution as a surfactant. The response/recovery times were about 5 s/8 s for 100 ppm ethanol and 4 s/20 s for 100 ppm H2S, respectively. Especially, the maximum response value of H2S is estimated to be 368 at 180 °C, which is one or two orders of magnitude higher than that of other test gases in this study. That indicates that the sensor fabricated with the help of polyvinyl pyrrolidone has good selectivity to H2S.

19.
Zhongguo Zhong Yao Za Zhi ; 43(14): 2872-2877, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30111044

RESUMO

To systematically identify the related substances in the original materials of breviscapine injection, 18 batches of samples collected from different pharmaceutical companies, its ethanol extract and breviscapine mother liquor concentrate were analyzed by high performance liquid chromatography (HPLC), and their structures were identified by ultra performance liquid chromatography and quadruple/time-of-flight mass spectrometry (UPLC-QTOF-MS). Under the selected chromatographic conditions, scutellarin and related substances have good resolution and 13 related substances were observed. Based on the molecular weight and fragmentation patterns obtained by UPLC-QTOF-MS as well as reference substances, their structures were elucidated as 6-hydroxyapigenin-6-O-glucosyl-7-O-glucuronide (1), 5,7,8,3',4',5'-hexahydroxyflavone-7-O-glucuronide (2), 5,6,7,3',4'-pentahydroxyflavone-7-O-glucuronide(3)and its isomer (4), patuletin-3-O-glucuronide (5), methoxylscutellarin (6), apigenin 7-O-glucuronide (7), isorhamnetin 7-O-glucuronide (8), diosmetin 7-O-glucuronide (9), scutellarein (10), scutellarin methyl ester (11), scutellarin ethyl ester (12), and apigenin (13). This study has clarified related substances in the original materials of breviscapine injection, providing references for the improvement of quality control for breviscapine drug material and its preparations.


Assuntos
Cromatografia Líquida de Alta Pressão , Flavonoides , Espectrometria de Massas
20.
Zhongguo Zhong Yao Za Zhi ; 43(14): 2979-2984, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30111058

RESUMO

To investigate the mechanism of n-butanol extract of Pulsatilla decoction (BAEB) against murine ulcerative colitis (UC) model induced by DSS combined with Candida albicans (CA) colonization, mice were randomly divided into normal control group, DSS group, DSS+CA group, BAEB high, medium and low dose group, and positive drug Mesalazine group. The general condition of mice was observed, fungal loads of murine intestinal contents were detected by plate method, colonic pathological change of mice was examined by HE staining. ASCA in serum and IL-6, IL-8, IL-1ß, HBD-2, HBD-3 in colonic mucosa were detected by ELISA. The results showed that, compared with DSS group, the general condition and ASCA in serum had no obvious change for DSS+CA group, but the fungal loads in intestinal contents, the colonic pathological damage, and the levels of IL-6, IL-8, IL-1ß, HBD-2, HBD-3 in colonic mucosa were greater than that of DSS group. High dose of BAEB group and Mesalazine group could improve the colonic pathology, decrease IL-6, IL-8, IL-1ß, HBD-2, HBD-3 expression level. In conclusion, BAEB could effectively improve the UC symptoms in mice induced by DSS combined with CA colonization, and inhibit the inflammatory factors such as IL-6, imply that BAEB is of important value for the treatment of intestinal fungal-related colitis.


Assuntos
Colite Ulcerativa , Pulsatilla , 1-Butanol , Animais , Candida albicans , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos
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