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1.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1743-1751, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982478

RESUMO

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.


Assuntos
Doença de Alzheimer , MicroRNAs , Doenças Neurodegenerativas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Humanos , Medicina Tradicional Chinesa , MicroRNAs/genética
2.
Plant Commun ; 1(1): 100001, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33404548

RESUMO

The genetic identities of Ca2+ channels in root hair (RH) tips essential for constitutive RH growth have remained elusive for decades. Here, we report the identification and characterization of three cyclic nucleotide-gated channel (CNGC) family members, CNGC5, CNGC6, and CNGC9, as Ca2+ channels essential for constitutive RH growth in Arabidopsis. We found that the cngc5-1cngc6-2cngc9-1 triple mutant (designated shrh1) showed significantly shorter and branching RH phenotypes as compared with the wild type. The defective RH growth phenotype of shrh1 could be rescued by either the expression of CNGC5, CNGC6, or CNGC9 single gene or by the supply of high external Ca2+, but could not be rescued by external K+ supply. Cytosolic Ca2+ imaging and patch-clamp data in HEK293T cells showed that these three CNGCs all function as Ca2+-permeable channels. Cytosolic Ca2+ imaging in growing RHs further showed that the Ca2+ gradients and their oscillation in RH tips were dramatically attenuated in shrh1 compared with those in the wild type. Phenotypic analysis revealed that these three CNGCs are Ca2+ channels essential for constitutive RH growth, with different roles in RHs from the conditional player CNGC14. Moreover, we found that these three CNGCs are involved in auxin signaling in RHs. Taken together, our study identified CNGC5, CNGC6, and CNGC9 as three key Ca2+ channels essential for constitutive RH growth and auxin signaling in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Cálcio/metabolismo , Cálcio/farmacologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Citosol/metabolismo , Células HEK293 , Humanos , Ácidos Indolacéticos/metabolismo , Mutação , Técnicas de Patch-Clamp , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Potássio/metabolismo , Potássio/farmacologia , Imagem com Lapso de Tempo
3.
Mol Cells ; 41(5): 401-412, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29754474

RESUMO

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.


Assuntos
Alcaloides/toxicidade , Antivirais/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Quinolizinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Alcaloides/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Antracenos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Butilaminas/farmacologia , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Chaperona BiP do Retículo Endoplasmático , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/enzimologia , Humanos , Fosforilação/efeitos dos fármacos , Quinolizinas/farmacologia
4.
JPEN J Parenter Enteral Nutr ; 41(5): 824-829, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-26407598

RESUMO

BACKGROUND: In the battle against Crohn's disease, autophagy stimulation is a promising therapeutic option-one both new and newly rediscovered. In experimental models, docosahexaenoic acid (DHA)-a long-chain polyunsaturated fatty acid-has been demonstrated to be useful in the treatment of inflammatory bowel disease through inhibition of the nuclear factor-κB pathway. However, the impact of DHA on autophagy in the colon remains unclear. METHODS: Mice were divided into 3 groups: wild type (placebo), the interleukin 10 knockout group (IL-10-/-, placebo), and the DHA group (IL-10-/-, DHA). DHA was administered to IL-10-/- mice by gavage at a dosage of 35.5 mg/kg/d for 2 weeks. The severity of colitis, expression of proinflammatory cytokines, expression/distribution of LC3B, and mTOR signaling pathway were evaluated in the proximal colon tissues collected from all mice at the end of the experiment. RESULTS: DHA administration ameliorated experimental colitis in the IL-10-/- mice, as demonstrated by decreased proinflammatory cytokines (TNF-α and IFN-γ), reduced infiltration of inflammatory cells, and lowered histologic scores of the proximal colon mucosa. Moreover, in the DHA-treated mice, enhanced autophagy was observed to be associated with (1) increased expression and restoration of the distribution integrity of LC3B in the colon and (2) inhibition of the mTOR signaling pathway. CONCLUSION: This study showed that DHA therapy could attenuate experimental chronic colitis in IL-10-/- mice by triggering autophagy via inhibition of the mTOR pathway.


Assuntos
Autofagia/efeitos dos fármacos , Colite/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-10/deficiência , Serina-Treonina Quinases TOR/genética , Animais , Doença Crônica , Colo/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
5.
Plant Signal Behav ; 12(11): e1197999, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-27322818

RESUMO

We recently revealed that cyclic nucleotide-gated channel 18 (CNGC18) functioned as the main Ca2+ channel in pollen tube tips for pollen tube guidance to ovules by regulating external Ca2+ influx in Arabidopsis. In this study, we found that the reduction of external Ca2+ concentration ([Ca2+]ext) from 10 mM to 5 mM, and further to 2 mM, led to the decreases of pollen germination percentages, but led to the increases of the percentages of ruptured pollen grains and tubes, and branched pollen tubes in vitro in cngc18-17 compared with wild type. The second point mutant allele cngc18-22 showed similar phenotypes, including reduced pollen germination percentages, increased percentages of ruptured pollen tubes, but did not show obvious different percentages of ruptured pollen grains and branched pollen tubes compared with wild type. These data demonstrate that CNGC18 plays essential roles in pollen germination and tube growth as a Ca2+ channel in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Germinação/fisiologia , Pólen/metabolismo , Pólen/fisiologia , Proteínas de Arabidopsis/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Germinação/genética , Pólen/genética , Tubo Polínico/genética , Tubo Polínico/metabolismo , Tubo Polínico/fisiologia
6.
International Eye Science ; (12): 2359-2362, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-669386

RESUMO

·AIM: To investigate the early effects of 3g/L sodium hyaluronate eye drops combined with soft contact lenses on corneal epithelial healing and local comfort.·METHODS: Totally 90 patients ( 90 eyes ) with primary monocular pterygium were randomly divided into three groups after pterygium excision surgeries ( n = 30, for each) . Each group received pterygium excision combined with limbal stem cell autograft transplantation. The research group wore soft corneal contact lens for 7d after the surgery, and the next day all of them were given 3g/L sodium hyaluronate and levofloxacin eye drops four times a day, tobrmycin and dexamethasone ophthalmic ointment once every night. The Group B did not wear the corneal contact lens, they were given levofloxacin eye drops four times a day and tobrmycin and dexamethasone ophthalmic ointment once every night. About the Group C, the 3g/L sodium hyaluronate eye drops was added on the basis of conventional medication of Group B. The time of corneal epithelial healing after surgery and the ocular pain score in different times were observed and contrasted.· RESULTS: Mean pain score of Group A were significantly lower than Group B and C at 6h, the first day and the third day after operation(P<0. 001), but there was no significant difference between the three groups at the fifth day and the seventh day (P>0. 05). The first day after the surgery, there were no eyes of corneal epithelium completely healed, but the complete healing rate of Group A were significantly higher than the other two group at the second day and the third day. (P<0. 05).·CONCLUSION: Early use of 3g/L hyaluronate sodium eye drops combined with soft corneal contact lenses after pterygium excision surgeries will not only accelerate corneal epithelial wound healing, but also relieve local pain, improve ocular comfort significantly.

7.
Environ Toxicol Pharmacol ; 45: 257-64, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27344125

RESUMO

Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide (AD), is obviously known to be nephrotoxicity, but AD has not been reported clearly. Our study aimed to investigate the induction of apoptosis in human renal tubular epithelial (HK-2) cells by AD and its possible mechanism. Our results demonstrated that AD (0-250µmol/L) inhibited Hk-2 cells proliferation in a dose- and time-dependent manner and induced apoptosis, accompanied by decreased of superoxide dismutase (SOD) activity and increased of malondialdehvde (MDA) content. Simultaneously, AD regulated the expression of endoplasmic reticulum (ER) molecular chaperone glucose-regulated protein 78 (GRP78/Bip) protein, elevated the expressions of C/EBP homologous protein (CHOP) and Caspase-4, indicating activation of ER stress signaling, and induced the alterative expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) proteins. It provided evidence that ER stress and inflammation would be significant mechanisms responsible for AD-induced apoptosis in addition to oxidative stress.


Assuntos
Apoptose/efeitos dos fármacos , Diterpenos/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/imunologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Receptor Celular 1 do Vírus da Hepatite A/biossíntese , Humanos , Interleucina-6/biossíntese , Túbulos Renais/imunologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Estrutura Molecular , Fator de Necrose Tumoral alfa/biossíntese
8.
Basic Clin Pharmacol Toxicol ; 119(4): 405-11, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27097917

RESUMO

Oxymatrine (OMT) is a traditional Chinese medicine monomer and has been used for the treatment of chronic viral hepatitis and many other diseases. We aimed to investigate whether OMT could induce hepatotoxicity in mice and explored the preliminary mechanisms of toxic effects. Twenty-four Institute for Cancer Research male mice were randomly divided into four groups: control group, 40, 160 and 320 mg/kg OMT-treated group. OMT was orally administered once daily for 7 days. The OMT-treated group exhibited an improved liver index and increase in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase,augmented liver histological injury, elevated levels of malondialdehyde and tumour necrosis factor alpha (TNF-α) accompanied by the activation of caspase-9/-8/-3, up-regulated expressions of tumour necrosis factor receptor l (TNFR1), TNF receptor-associated structure domain (TRADD) and phosphorylation of stress-activated protein kinase/c-jun N-terminal protein kinases (p-SAPK/JNK). Altogether, these results suggest that OMT at a dose of 320 mg/kg leads to liver damage and is related to the activation of JNK signalling pathway mediated by TNF-α in the liver of mice.


Assuntos
Alcaloides/efeitos adversos , Antiarrítmicos/efeitos adversos , Antivirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinolizinas/efeitos adversos , Alcaloides/administração & dosagem , Animais , Antiarrítmicos/administração & dosagem , Antivirais/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Masculino , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Quinolizinas/administração & dosagem , Distribuição Aleatória , Receptores Tipo I de Fatores de Necrose Tumoral/agonistas , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Proteína de Domínio de Morte Associada a Receptor de TNF/agonistas , Proteína de Domínio de Morte Associada a Receptor de TNF/genética , Proteína de Domínio de Morte Associada a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Proc Natl Acad Sci U S A ; 113(11): 3096-101, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26929345

RESUMO

In flowering plants, pollen tubes are guided into ovules by multiple attractants from female gametophytes to release paired sperm cells for double fertilization. It has been well-established that Ca(2+) gradients in the pollen tube tips are essential for pollen tube guidance and that plasma membrane Ca(2+) channels in pollen tube tips are core components that regulate Ca(2+) gradients by mediating and regulating external Ca(2+) influx. Therefore, Ca(2+) channels are the core components for pollen tube guidance. However, there is still no genetic evidence for the identification of the putative Ca(2+) channels essential for pollen tube guidance. Here, we report that the point mutations R491Q or R578K in cyclic nucleotide-gated channel 18 (CNGC18) resulted in abnormal Ca(2+) gradients and strong pollen tube guidance defects by impairing the activation of CNGC18 in Arabidopsis. The pollen tube guidance defects of cngc18-17 (R491Q) and of the transfer DNA (T-DNA) insertion mutant cngc18-1 (+/-) were completely rescued by CNGC18. Furthermore, domain-swapping experiments showed that CNGC18's transmembrane domains are indispensable for pollen tube guidance. Additionally, we found that, among eight Ca(2+) channels (including six CNGCs and two glutamate receptor-like channels), CNGC18 was the only one essential for pollen tube guidance. Thus, CNGC18 is the long-sought essential Ca(2+) channel for pollen tube guidance in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Cálcio/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/fisiologia , Tubo Polínico/crescimento & desenvolvimento , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Canais de Cálcio/fisiologia , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/química , Canais de Cátion Regulados por Nucleotídeos Cíclicos/deficiência , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Genes Reporter , Teste de Complementação Genética , Células HEK293 , Humanos , Potenciais da Membrana , Mutação de Sentido Incorreto , Óvulo Vegetal , Técnicas de Patch-Clamp , Infertilidade das Plantas/genética , Plantas Geneticamente Modificadas , Mutação Puntual , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Sistemas do Segundo Mensageiro
10.
Chinese Medical Journal ; (24): 1200-1207, 2016.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-290102

RESUMO

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) are bone marrow stem cells which play an important role in tissue repair. The treatment with MSCs will be likely to aggravate the degree of fibrosis. The Wnt/β-catenin signaling pathway is involved in developmental and physiological processes, such as fibrosis. Dickkopfs (DKKs) are considered as an antagonist to block Wnt/β-catenin signaling pathway by binding the receptor of receptor-related protein (LRP5/6). DKK1 was chosen in attempt to inhibit fibrosis of MSCs by lowering activity of Wnt/β-catenin signaling pathway.</p><p><b>METHODS</b>Stable MSCs were randomly divided into four groups: MSCs control, MSCs + transforming growth factor-β (TGF-β), MSCs + DKK1, and MSCs + TGF-β + DKK1. Flow cytometry was used to identify MSCs. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide test. Immunofluorescence was used to detect protein expression in the Wnt/β-catenin signaling pathways. Western blotting analysis was employed to test expression of fibroblast surface markers and, finally, real-time reverse transcription polymerase chain reaction was employed to test mRNA expression of fibroblast surface markers and Wnt/β-catenin signaling proteins.</p><p><b>RESULTS</b>Cultivated MSCs were found to conform to the characteristics of standard MSCs: expression of cluster of differentiation (CD) 73, 90, and 105, not expression of 34, 45, and 79. We found that DKK1 could maintain the normal cell morphology of MSCs. Western blotting analysis showed that fibroblast surface markers were expressed in high quantities in the group MSCs + TGF-β. However, the expression was lower in the MSCs + TGF-β + DKK1. Immunofluorescence showed high expression of all Wnt/β-catnin molecules in the MSCs + TGF-β group but expressed in lower quantities in MSCs + TGF-β + DKK1 group. Finally, mRNA expression of fibroblast markers vimentin, α-smooth muscle actin and Wnt/β-catenin signaling proteins β-catenin, T-cell factor, and glycogen synthase kinase-3β was significantly increased in MSCs + TGF-β group compared to control (P < 0.05). Expression of the same fibroblast markers and Wnt/β-catenin was decreased to regular quantities in the MSCs + TGF-β + DKK1 group.</p><p><b>CONCLUSIONS</b>DKK1, Wnt/β-catenin inhibitors, blocks the Wnt/β-catenin signaling pathway to inhibit the process of MSCs fibrosis. It might provide some new ways for clinical treatment of certain diseases.</p>


Assuntos
Animais , Feminino , Camundongos , Ratos , Diferenciação Celular , Fisiologia , Células Cultivadas , Fibroblastos , Biologia Celular , Metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Genética , Metabolismo , Células-Tronco Mesenquimais , Biologia Celular , Metabolismo , Fator de Crescimento Transformador beta , Genética , Metabolismo
11.
Environ Toxicol Pharmacol ; 40(2): 592-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26356389

RESUMO

Our previous works have indicated that the mitochondrion is the primary target of nephrotoxicity induced by andrographolide sodium bisulfate (ASB), but the mechanisms of ASB-induced nephrotoxicity have remained largely unknown. In this study, proteomic analysis was used to explore the changes in the renal mitochondrial proteome in SD rats after treatment with ASB. SD rats were intraperitoneally administered with ASB (100, 600mg/kg/d) for 7 days. Renal impairment was evaluated by pathological observation. Two-dimensional gel electrophoresis (2-DE), as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS), was applied for the identification of mitochondrial protein and was validated by Western blotting. Protein-protein interactions were analyzed using a Web-based bioinformatics tool (STRING, version 9.1). Rat kidneys exhibited histopathological changes after treatment with ASB, and 13 proteins were significantly changed, including ES1 protein homolog, heat shock cognate 71kDa protein, peroxiredoxin-1 (Prdx1), cytochrome C oxidase subunit 5B (COX5B), prohibitin (PHB), threonine-tRNA ligase, pyruvate dehydrogenase E1 component subunit beta (PDH-ß), voltage-dependent anion-selective channel protein 2 (VDAC2), voltage-dependent anion-selective channel protein 1 (VDAC1), adenylate kinase 2 (KAD2) and others. These data demonstrated that the expression levels of several proteins significantly changed in the mitochondria, and these proteins could be candidate biomarkers for ASB-induced nephrotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Proteínas Mitocondriais/metabolismo , Sulfitos/toxicidade , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Proteínas Mitocondriais/efeitos dos fármacos , Proibitinas , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sulfitos/administração & dosagem
12.
World J Gastroenterol ; 21(27): 8373-81, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26217089

RESUMO

AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) patients. METHODS: This was a retrospective study of 1457 patients hospitalized for CHB between October 2008 and October 2013 at the Beijing Ditan Hospital, Capital Medical University, China. The patients were divided into two groups: severe acute exacerbation (SAE) group (n = 382) and non-SAE group (n = 1075). The SAE group was classified as the high-risk group based on the higher incidence of ACLF in this group than in the non-SAE group (13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned to risk-model derivation and the other one-third to model validation. Univariate risk factors associated with the outcome were entered into a multivariate logistic regression model for screening independent risk factors. Each variable was assigned an integer value based on the regression coefficients, and the final score was the sum of these values in the derivation set. Model discrimination and calibration were assessed using area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The risk prediction scoring model included the following four factors: age ≥ 40 years, total bilirubin ≥ 171 µmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 10(7) copies/mL. The sum risk score ranged from 0 to 7; 0-3 identified patients with lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan-Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the two risk groups (0-3 and 4-7 scores) of the primary cohort over 56 d, and log-rank test revealed a significant difference (2.0% vs 33.8% and 0.8% vs 9.4%, respectively; both P < 0.0001). In the derivation and validation data sets, the model had good discrimination (C index = 0.857, 95% confidence interval: 0.800-0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively) and calibration demonstrated by the Hosmer-Lemeshow test (χ (2) = 4.516, P = 0.808 and χ (2) = 1.959, P = 0.923, respectively). CONCLUSION: Using the scoring model, clinicians can easily identify patients (total score ≥ 4) at high risk of ACLF and ACLF-related death early during SAE.


Assuntos
Insuficiência Hepática Crônica Agudizada/virologia , Técnicas de Apoio para a Decisão , Hepatite B Crônica/complicações , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Fatores Etários , Área Sob a Curva , Bilirrubina/sangue , Biomarcadores/sangue , Distribuição de Qui-Quadrado , China , DNA Viral/genética , Progressão da Doença , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/mortalidade , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Protrombina/análise , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Carga Viral
13.
Br J Nutr ; 114(2): 181-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26104043

RESUMO

A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.


Assuntos
Colite/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/administração & dosagem , Interleucina-10/genética , Intestinos/efeitos dos fármacos , Animais , Apoptose , Colite/patologia , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interferon gama/metabolismo , Interleucina-10/deficiência , Interleucina-17/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Ocludina/genética , Ocludina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
14.
Int Immunopharmacol ; 26(1): 221-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25858875

RESUMO

BACKGROUND: Celastrol had been proved effective in the treatment for IBD, probably with the modulation of oxidative stress, inflammatory cytokines and intestinal homeostasis. This study was aimed to investigate whether celastrol could ameliorate the inflammation of IL-10 deficient mice, a murine model of Crohn's disease (CD) with the induction of autophagy. MATERIAL AND METHODS: The mice included were divided into four groups, ##WT group, IL-10(-/-) group, Cel group and Control group (celastrol+3-Methyladenine). Celastrol (2 mg/kg) treatment by gavage was administered to mice daily over one week. 3-Methyladenine (autophagy inhibitors) was administered at a dose of 30 mg/kg by intraperitoneal injection. The histological evaluation of the colon, tissue myeloperoxidase (MPO), and colon inflammation of mice in the four groups was evaluated and compared. Furthermore, the PI3K/Akt/mTOR pathway and the status of autophagy in intestine affected by celastrol were also assessed. RESULTS: The one-week administration of celastrol ameliorated established colitis in IL-10 deficient mice, associated with a reduction of marked histological inflammation, a decreased colon MPO concentration and suppression of colonic proinflammatory cytokine. Furthermore, the decreased neutrophil infiltration in proximal colon and improvement of inflammation in the Cel group was much more obvious than that in the Control group. The Western blotting analysis of the PI3K/Akt/mTOR pathway and autophagy showed that celastrol treatment up-regulated the autophagy of colon tissue by suppressing the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy by suppressing the PI3K/Akt/mTOR signaling pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , Autofagia/efeitos dos fármacos , Colo/efeitos dos fármacos , Doença de Crohn/tratamento farmacológico , Interleucina-10/deficiência , Triterpenos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Western Blotting , Colo/imunologia , Colo/patologia , Doença de Crohn/imunologia , Doença de Crohn/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Interleucina-10/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Triterpenos Pentacíclicos , Peroxidase/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Triterpenos/administração & dosagem
15.
World J Gastroenterol ; 21(4): 1299-304, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25632205

RESUMO

AIM: To investigate the impact of enteral nutrition (EN) on the body composition and metabolism in patients with Crohn's disease (CD). METHODS: Sixty-one patients diagnosed with CD were enrolled in this study. They were given only EN (enteral nutritional suspension, TPF, non-elemental diet) support for 4 wk, without any treatment with corticosteroids, immunosuppressive drugs, infliximab or by surgical operation. Body composition statistics such as weight, body mass index, skeletal muscle mass (SMM), fat mass, protein mass and inflammation indexes such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and CD activity index (CDAI) were recorded before and after EN support. RESULTS: The 61 patients were divided into three groups according to CDAI before and after EN support: A (active phase into remission via EN, n=21), B (remained in active phase before and after EN, n=19) and C (in remission before and after EN, n=21). Patients in group A had a significant increase in SMM (22.11±4.77 kg vs 23.23±4.49 kg, P=0.044), protein mass (8.01±1.57 kg vs 8.44±1.45 kg, P=0.019) and decrease in resting energy expenditure (REE) per kilogram (27.42±5.01 kcal/kg per day vs 22.62±5.45 kcal/kg per day, P<0.05). There was no significant difference between predicted and measured REE in active CD patients according to the Harris-Benedict equation. There was no linear correlation between the measured REE and CRP, ESR or CDAI in active CD patients. CONCLUSION: EN could decrease the hypermetabolism in active CD patients by reducing the inflammatory response.


Assuntos
Doença de Crohn/terapia , Metabolismo Energético , Nutrição Enteral , Adulto , Biomarcadores/sangue , Composição Corporal , China , Doença de Crohn/diagnóstico , Doença de Crohn/metabolismo , Doença de Crohn/fisiopatologia , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(3): 757-61, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-25208407

RESUMO

In the present paper, a method of monitoring progressive damage of composite structures by non-uniform fiber Bragg grating (FBG) reflection spectrum is proposed. Due to the finite element analysis of corrugated composite skins specimens, the failure process under tensile load and corresponding critical failure loads of corrugated composite skin was predicated. Then, the non-uniform reflection spectrum of FBG sensor could be reconstructed and the corresponding relationship between layer failure order sequence of corrugated composite skin and FBG sensor reflection spectrums was acquired. A monitoring system based on FBG non-uniform reflection spectrum, which can be used to monitor progressive damage of corrugated composite skins, was built. The corrugated composite skins were stretched under this FBG non-uniform reflection spectrum monitoring system. The results indicate that real-time spectrums acquired by FBG non-uniform reflection spectrum monitoring system show the same trend with the reconstruction reflection spectrums. The maximum error between the corresponding failure and the predictive value is 8.6%, which proves the feasibility of using FBG sensor to monitor progressive damage of corrugated composite skin. In this method, the real-time changes in the FBG non-uniform reflection spectrum within the scope of failure were acquired through the way of monitoring and predicating, and at the same time, the progressive damage extent and layer failure sequence of corru- gated composite skin was estimated, and without destroying the structure of the specimen, the method is easy and simple to operate. The measurement and transmission section of the system are completely composed of optical fiber, which provides new ideas and experimental reference for the field of dynamic monitoring of smart skin.

18.
Zhonghua Wai Ke Za Zhi ; 51(2): 139-41, 2013 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-23711007

RESUMO

OBJECTIVE: To investigate diagnosis and treatment of abdominal cocoon. METHODS: Clinical data of patients received treatment for abdominal cocoon from January 2000 to January 2011 was retrospectively analyzed. RESULTS: A total of 67 patients underwent treatment in our hospital were analyzed, the preoperatively diagnosis rate was only 47.8% (32/67). Patients who received preoperatively nutrition support have a lower postoperative complication (8/27 vs.13/20, χ(2) = 5.815, P < 0.05) and patients with less extent of intestine involved had a lower early postoperative inflammatory ileus (EPII) rate (9/25 vs. 1/22, χ(2) = 6.912, P < 0.05) when compared with large extent. CONCLUSIONS: Appropriate perioperative management play an important role in the prognosis of abdominal cocoon. The main treatment is surgery while preoperatively nutrition support can reduce postoperative complications.


Assuntos
Íleus/prevenção & controle , Fibrose Peritoneal/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
19.
Zhong Xi Yi Jie He Xue Bao ; 10(11): 1211-28, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23158939

RESUMO

BACKGROUND: Chronic severe hepatitis is a critical disease with high mortality. Currently, effective drugs and therapy still lack. Comprehensive and supportive treatment, artificial liver and liver transplantation are the main therapies. A great number of studies on traditional Chinese medicine (TCM) in many ways combined with Western medicine treatment for chronic severe hepatitis have been reported, but the efficacy and safety still lack systematic evaluation. OBJECTIVE: To evaluate the efficacy and safety of integrative medicine therapy for chronic severe hepatitis. SEARCH STRATEGY: Literature was searched from PubMed, the Cochrane Library, the China National Knowledge Infrastructure Database, the Chongqing VIP Chinese Science and Technology Periodical Database, the Chinese Biomedical Literature Database and Wanfang Database. The time limitation ran from the commencement of each database to February 29, 2012. INCLUSION CRITERIA: Randomized controlled trials (RCTs) testing Chinese herbal medicine (CHM) combined with Western medicine (comprehensive and supportive treatment or artificial liver plasma exchange) against Western medicine were included. DATA EXTRACTION AND ANALYSIS: Two authors collected and extracted data independently. The methodological quality of literature was assessed by risk of bias table from Cochrane Collaboration and the data were analyzed by RevMan 5.1 software. Heterogeneity of the included studies was checked by Chi-square test. The efficacy measure was relative risk (RR) or mean difference with a 95% confidence interval (CI). RESULTS: A total of 45 RCTs involving 4 449 patients with chronic severe hepatitis were included. Quality of all included trials was low. The oral CHM, enema and combined TCM with either Western medicine or plasma exchange were superior to Western medicine alone in improving total effective rate and reducing mortality with significant differences. In laboratory parameters, the integrative medicine treatment group was better than Western control group in reducing the total bilirubin and alanine aminotransferase, but two groups showed equal efficacy in lowering aspartate aminotransferase activity. The oral Chinese medicine combined with Western medicine or plasma exchange was better than Western medicine used alone in improving albumin synthesis and coagulation function, but Chinese medicine enema had no significant effect on the level of plasma albumin. The main side effects of the treatment group were abdominal pain, diarrhea and other intestinal symptoms after enema, while adverse reactions of the control group were mainly due to the plasma exchange. CONCLUSION: Integrated Chinese and Western medicine can promote the recovery of liver function and coagulation function, and reduce the mortality rate of patients with chronic severe hepatitis. However, due to a lower quality of clinical trials published in Chinese journals, the evidence is insufficient to prove the superiority of integrative therapy. Further well-designed, multicenter, large-sample RCTs are still needed to evaluate the beneficial effects of CHM.


Assuntos
Hepatite Crônica/terapia , Medicina Integrativa , Terapias Complementares , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Zhonghua Yan Ke Za Zhi ; 46(2): 129-33, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20388346

RESUMO

OBJECTIVE: To study clinical characteristics, treatment and prognosis of syphilitic posterior uveitis. METHODS: A retrospective study was conducted in 26 patients with syphilitic posterior uveitis. The diagnosis was confirmed by clinical and laboratory tests. RESULTS: There were 26 patients, 16 males and 10 females, mean age was 40 years. Fourteen patients were bilateral. The symptoms included impaired vision and floaters. In 40 eyes, yellow-white lesions in the posterior pole were present in 8 eyes, 22 eyes showed mild congestion of optic discs and loss of reflex in the fovea, and 6 eyes showed significant congestion and swelling of the optic disc. Fluorescein angiography showed staining or hyperfluorescence of optic disc in 40 eyes, venous leakage in 26 eyes, retinal pigment epithelium damage with dye pooling in 6 eyes, and cystoid macular edema in 6 eyes. ICGA: squamous or disseminative hypofluorescence damage was present in all 40 eyes. After the treatment, 32 eyes had improved vision and fundus damage. CONCLUSIONS: Syphilitic posterior uveitis has typical symptoms and signs. This is a curable disease, early diagnosis and prompt treatment are important for the improvement of prognosis.


Assuntos
Sífilis/diagnóstico , Sífilis/terapia , Uveíte Posterior/diagnóstico , Uveíte Posterior/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Treponema pallidum , Uveíte Posterior/microbiologia , Adulto Jovem
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