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1.
Chin J Integr Med ; 29(6): 483-489, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36971885

RESUMO

OBJECTIVE: To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial. METHODS: This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments. RESULTS: During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group. CONCLUSIONS: CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).


Assuntos
Medicina Tradicional Chinesa , Infecção da Ferida Cirúrgica , Gravidez , Feminino , Humanos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/etiologia , Antibacterianos/uso terapêutico , Cesárea/efeitos adversos , Método Duplo-Cego , Resultado do Tratamento
2.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35217618

RESUMO

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN), causing bradykinesia and rest tremors. Although the molecular mechanism of PD is still not fully understood, neuroinflammation has a key role in the damage of dopaminergic neurons. Herein, we found that kurarinone, a unique natural product from Sophora flavescens, alleviated the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic neurotoxicity, including the losses of neurotransmitters and tyrosine hydroxylase (TH)-positive cells (SN and striatum [STR]). Furthermore, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia involved in the nuclear factor kappa B signaling pathway. The proteomics result of the solvent-induced protein precipitation and thermal proteome profiling suggest that the soluble epoxide hydrolase (sEH) enzyme, which is associated with the neuroinflammation of PD, is a promising target of kurarinone. This is supported by the increase of plasma epoxyeicosatrienoic acids (sEH substrates) and the decrease of dihydroxyeicosatrienoic acids (sEH products), and the results of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH revealed that this natural compound is an uncompetitive inhibitor. In addition, sEH knockout (KO) attenuated the progression of PD, and sEH KO plus kurarinone did not further reduce the protection of PD in MPTP-induced PD mice. These findings suggest that kurarinone could be a potential natural candidate for the treatment of PD, possibly through sEH inhibition.


Assuntos
Epóxido Hidrolases/metabolismo , Flavonoides/uso terapêutico , Doença de Parkinson/prevenção & controle , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Modelos Animais de Doenças , Epóxido Hidrolases/genética , Deleção de Genes , Camundongos , Microglia/efeitos dos fármacos , Especificidade por Substrato
3.
Food Chem Toxicol ; 156: 112516, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411643

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by dementia. Inhibition of soluble epoxide hydrolase (sEH) regulates inflammation involving in central nervous system (CNS) diseases. However, the exactly mechanism of sEH in AD is still unclear. In this study, we evaluated the vital role of sEH in amyloid beta (Aß)-induced AD mice, and revealed a possible molecular mechanism for inhibition of sEH in the treatment of AD. The results showed that the sEH expression and activity were remarkably increased in the hippocampus of Aß-induced AD mice. Chemical inhibition of sEH by TPPU, a selective sEH inhibitor, alleviated spatial learning and memory deficits, and elevated levels of neurotransmitters in Aß-induced AD mice. Furthermore, inhibition of sEH could ameliorate neuroinflammation, neuronal death, and oxidative stress via stabilizing the in vivo level of epoxyeicosatrienoic acids (EETs), especially 8,9-EET and 14,15-EET, further resulting in the anti-AD effect through the regulation of GSK3ß-mediated NF-κB, p53, and Nrf2 signaling pathways. These findings revealed the underlying mechanism of sEH as a potential therapeutic target in treatment of AD.


Assuntos
Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/toxicidade , Eicosanoides/metabolismo , Epóxido Hidrolases/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Animais , Epóxido Hidrolases/genética , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Transtornos da Memória , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Aprendizagem Espacial/efeitos dos fármacos
4.
Phytomedicine ; 81: 153436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360346

RESUMO

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Uncaria/química , Hormônio Adrenocorticotrópico/sangue , Animais , Antidepressivos/química , Biologia Computacional , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Depressão/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Receptor 5-HT1A de Serotonina , Serotonina/metabolismo , Estresse Psicológico
5.
Ying Yong Sheng Tai Xue Bao ; 31(1): 239-248, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957401

RESUMO

With Tongxin, Xiji, and Longde counties in the mountainous area of southern Ningxia as the research area, we used extended-exergy analysis (EEA) to compare their ecological efficiency driving mechanism in 2008-2017 to explore the causes of their variation in ecological degradation. The results showed that the overall difference of ecological efficiency in the three counties was significant during the study period. The ecological efficiency of Tongxin was low, with large inter-annual variation. The ecological efficiency of Xiji was stable, and the overall efficiency of Longde was the highest. The difference of exergy scale was small among the three counties. The exergy proportion in the economic sectors was not coordinated, which were dominated by agricultural and residential sectors. The economic sectors presented significant capital-pull-type and labor-intensive characteristics, indicating the driving force for ecological degradation mainly came from agricultural production and residents' lives in underdeveloped regions. The system's internal exergy conversion rate and the external energy exchange rate of the three counties were extremely low, constituting a simple network circulation path with high input, low storage, low opening and low conversion, which weakened the endogenous development of social economic subsystem and threatened the fragile ecosystem.


Assuntos
Ecologia , Ecossistema , Agricultura , China , Eficiência
6.
J Food Sci ; 84(9): 2658-2665, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31441515

RESUMO

Hepatic injury is one of the most common digestive system diseases worldwide in clinic. Guanylic acid or guanosine monophosphate (GMP) was an important component of nucleotides, which is mainly in the form of sodium salt (disodium guanylate, GMP-Na2 ). However, its effect on hepatic injury has not yet been investigated. This study is to investigate the protective effects of GMP-Na2 on acute hepatic injury induced by carbon tetrachloride (CCl4 ), and to explore its mechanism. The hepatic injury models of mice and HL-7702 cells were induced by CCl4 . The alanine transaminase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (T-AOC) were determined by biochemical method. Hematoxylin-eosin staining were used to determine the morphological changes on liver tissue in mice. The mRNA and protein expressions of caspase-3, Bax, and Bcl-2 were detected by RT-PCR and Western blot analysis. Our results show that GMP-Na2 treatment significantly decreased the activities of ALT and AST, and the levels of MDA as well as increased the levels of SOD, GSH-Px, and T-AOC. Importantly, GMP-Na2 effectively enhanced the antiapoptosis function by upregulating Bcl-2 expression and downregulating caspase-3 and Bax expressions in vivo and in vitro. Moreover, the histopathological changes of liver tissue were obviously improved after GMP-Na2 treatment. These findings suggest that GMP-Na2 has protective effects on hepatic injury, and its mechanisms may be associated with antioxidative stress and antiapoptosis.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Guanosina Monofosfato/farmacologia , Fígado/efeitos dos fármacos , Animais , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos
7.
J Int Med Res ; 47(5): 2145-2156, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30966824

RESUMO

OBJECTIVE: This study was performed to assess the clinical feasibility, safety, and effectiveness of a computed tomography (CT)-guided cyanoacrylate injection system and investigate the relationship between clinical features and pathologic characteristics of diminutive pulmonary lesions. METHODS: In total, 115 pulmonary nodules from 113 patients (63 female, 50 male) with a diameter of <20 mm were percutaneously localized with a CT-guided cyanoacrylate injection system and then resected. RESULTS: Of the pure ground-glass opacities (GGOs), 16.0% were atypical adenomatous hyperplasia (AAH), 18.7% were adenocarcinoma in situ (AIS), 49.3% were lung adenocarcinoma (ADC), and 16.0% were benign inflammatory fibrosis/fibrotic scars. Of the mixed GGOs, 18.2% were AAH, 22.7% were AIS, 22.7% were ADC, and 36.4% were benign lesions. Lesions of >10 mm and those located in relation to vessels were significantly more likely to be malignant. The success rate of both the cyanoacrylate injection system and video-assisted thoracoscopic surgery was 100% with no severe complications. CONCLUSIONS: Preoperative localization of small pulmonary nodules using a cyanoacrylate injection system is a safe, simple, and useful technique.


Assuntos
Cianoacrilatos/administração & dosagem , Injeções , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Cianoacrilatos/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Carga Tumoral
8.
Int J Biol Macromol ; 131: 201-208, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30872054

RESUMO

In our search for natural human carboxylesterase 2 (hCE 2) inhibitors from natural products, we investigated inhibitory effects and mechanisms of flavonoids (1-16) against hCE 2. The results demonstrated that kurarinone (1), baicalein (2), 2-[(2'-(1-hydroxy-1-methylethyl)-7'-(3-methyl-2-butenyl)-2',3'-dihydrobenzofuran)-5-yl]-7-hydroxy-8-(3-methyl-2-butenyl)chroman-4-one (5), luteolin (6), kushenol X (9), and kushenol C (11) displayed significantly inhibitory effects against hCE 2 with IC50 values of 1.46 ±â€¯0.43, 5.22 ±â€¯0.89, 1.13 ±â€¯0.19, 9.78 ±â€¯0.98, 3.05 ±â€¯0.46, and 2.61 ±â€¯0.52 µM, respectively. Compounds 1, 5, 6, 9, and 11 were all uncompetitive inhibitors with Ki values of 1.73, 1.59, 16.89, 1.72, and 0.79 µM, respectively, and their Km values ranged from 2.08 µM to 5.41 µM. Furthermore, molecular docking was conducted for investigating mechanisms of compounds 1, 5, 6, 9, and 11 with hCE 2. These results suggested that compounds 1, 5, 6, 9, and 11 could be served as lead compounds for the development of novel hCE 2 inhibitors.


Assuntos
Carboxilesterase/antagonistas & inibidores , Carboxilesterase/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Hidrólise , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Estrutura-Atividade
9.
Cell Physiol Biochem ; 47(4): 1453-1464, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29940559

RESUMO

BACKGROUND/AIMS: Uncaria rhynchophylla, known as "Gou-teng", is a traditional Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions, and pacify the liver. Although U. rhynchophylla has a long history of being often used to treat central nervous system (CNS) diseases, its efficacy and potential mechanism are still uncertain. This study investigated neuroprotective effect and the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH-SY5Y cells and MPTP-induced mice. METHODS: MPP+-induced SH-SY5Y cells and MPTP-induced mice were used to established Parkinson's disease (PD) models. Quantitative proteomics and bioinformatics were used to uncover proteomics changes of URE. Western blotting was used to validate main differentially expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy-related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay were further used to confirm the effect of URE on MPP+-induced apoptosis in SH-SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP-induced mice. The levels of dopamine (DA) and their metabolites were examined in striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH) was detected by immunohischemical staining and Western blotting. RESULTS: URE dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells. Quantitative proteomics and bioinformatics results confirmed that HSP90 was an important differentially expressed protein of URE. URE inhibited the expression of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K p110α, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38, and LC3-II. URE also markedly decreased the apoptotic ratio and elevated mitochondrial transmembrane potential (DΨm). Furthermore, URE treatment ameliorated behavioral impairments, increased the contents of DA and its metabolites and elevated the positive expressions of TH in SN and STR as well as the TH protein. CONCLUSIONS: URE possessed the neuroprotective effect in vivo and in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD treatment.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Choque Térmico HSP90/biossíntese , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos , Uncaria/química , Animais , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/química , Humanos , Camundongos , Fármacos Neuroprotetores/química , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Proteômica
10.
Int J Surg ; 53: 143-150, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29555533

RESUMO

BACKGROUND: This study was performed to retrospectively evaluate the 10-year overall survival (OS), progression-free survival (PFS), and local control rates of patients with inoperable stage Ia non-small cell lung cancer (NSCLC) who underwent computed tomography (CT)-guided radiofrequency ablation (RFA) in a single center. MATERIALS AND METHODS: Fifty patients with inoperable NSCLC underwent RFA between 2004 and 2016. Thoracic surgeons evaluated the patients and performed RFA under CT guidance. Follow-up CT and positron emission tomography/CT scans were obtained. Local control rates and recurrence patterns were analyzed. RESULTS: Seventy-three lesions in 50 patients (M:F = 22:28; median age: 73 years; range: 52-82 years) were treated with CT-guided RFA. The mean lesion size was 2.2 cm (range: 1-3 cm). No procedure-related deaths occurred. Low-grade fever was the most common post-ablation complication, with an incidence rate of 36%. The 1-, 2-, 3-, 5-, and 10-year OS rates of patients with Ia NSCLC were 96.0%, 86.5%, 67.1%, 36.3%, and 1%, respectively, and the 1-, 2-, 3-, and 5-year PFS rates were 94.0%, 77.5%, 43.5%, and 10.8%, respectively. The most common pattern of recurrence was local, and 15 patients with recurrence were treated with repeat RFA. Tumor size <2.0 cm was associated with a significantly improved 3-year survival rate of 78.9%. CONCLUSION: CT-guided RFA is feasible and well tolerated by inoperable patients with inoperable stage Ia NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Ablação por Cateter , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
11.
Acad Radiol ; 24(12): 1517-1525, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28888381

RESUMO

RATIONALE AND OBJECTIVES: The aim of the study was to evaluate the overall survival (OS) rate, progression survival rate, and local control rate over 10 years of medically inoperable patients with lung cancer undergoing computed tomography (CT)-guided radiofrequency ablation (RFA). MATERIALS AND METHODS: Between September 2004 to March 2016, 668 neoplasms were treated in 476 medically inoperable patients (294 men, 60 women; median age 74 years; range 29-84) who underwent CT-guided RFA. All patients had clinical or pathologic evidence of the neoplastic lesion: 22.1% patients with primary non-small cell lung cancer (NSCLC), 22.3% patients with recurrent NSCLC, 45.2% with metastases, and 10.3% with small cell lung cancer. The mean size of the lesions was 3.8 cm (range of 1-16 cm). Twenty-one lesions were re-treated from one to as many as four times. RESULTS: The procedure was technically successful in all cases. No procedure-related deaths occurred in the RFA procedures. Major complications consisted in 104 (21.8%) cases of low-grade fever, 46 (9.6%) of the pneumothorax. The mean follow-up was 32 months. The probabilities of 1-, 2-, 3-, 5-, and 10-year OS rate were 98.1%, 86.6%, 68.9% 34.5%, and 9.5% for primary NSCLC; 59.7%, 18.5%, 8%, 3.4%, and 1.5% for metastases; 93.3%, 59.1%, 49.6%, 19.7%, and 0% for recurrence; and 89.4%, 67.5%, 39.1%, 16.5%, and 0% for small cell lung cancer. In primary NSCLC, progression-free survival (PFS) and OS were significantly related to tumor size, but there was no significant difference in recurrent NSCLC, metastasis, and peripheral SCLC. The median OS of metastases of NSCLC was significantly related to nodal or distant metastases. The most common pattern of recurrence was local; any type of recurrence at 1-year follow-up imaging was seen in 7.1% of primary NSCLC diameter less than 3 cm. CONCLUSIONS: Our experience indicates that CT-guided RFA done by the thoracic surgeons is feasible and safe in high-risk patients. Maximum tumor diameter less than 3 cm and lack of extrapulmonary metastasis are all positive prognostic factors of survival after RFA. RFA offers good local control of recurrent NSCLC, lung metastases, and SCLC, also in the long-term period. RFA should continue to offer an alternative option in medically inoperable patients.


Assuntos
Ablação por Cateter , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Radiografia Intervencionista , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
12.
Acta Crystallogr F Struct Biol Commun ; 72(Pt 1): 49-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26750484

RESUMO

Translocated intimin receptor (Tir) is an Escherichia coli-encoded protein that is transported into the host cell through a sophisticated bacterial type III secretion system (T3SS). Tir anchors the infected cell membrane twice using both its N- and C-termini from inside the host cytoplasm for signalling. It plays a key role in enterohemorrhagic Escherichia coli (EHEC) infection, attaching and effacing (A/E) lesions and intracellular signal transduction. Here, the overexpression, purification and crystallization of its N-terminal intracellular domain are reported. The crystal belonged to the orthorhombic space group I4122, with unit-cell parameters a = b = 59.79, c = 183.11 Å. The asymmetric unit contained one molecule, with a solvent content of 51% and a VM of 2.55 Å(3) Da(-1).


Assuntos
Proteínas de Escherichia coli/química , Escherichia coli , Receptores de Superfície Celular/química , Cristalização , Cristalografia por Raios X , Proteínas de Escherichia coli/biossíntese , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/isolamento & purificação , Expressão Gênica , Domínios Proteicos , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/isolamento & purificação , Sistemas de Secreção Tipo III
13.
Onco Targets Ther ; 8: 3383-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26604795

RESUMO

AIM: To evaluate the efficacy and safety of using nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) in the primary treatment of locoregionally advanced nasopharyngeal carcinoma. METHODS: Between December 2009 and December 2013, 38 newly diagnosed patients with stage III-IV nasopharyngeal carcinoma were treated with IMRT and nimotuzumab concomitantly. The distribution of disease was stage III in 20 (52.6%), stage IV A in 9 (23.7%), and stage IV B in 9 (23.7%). All the patients received at least two cycles of cisplatin-based neoadjuvant chemotherapy followed by nimotuzumab 200 mg/week concurrently with IMRT. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. RESULTS: With a median follow-up of 39.7 months (range, 13.3-66.5 months), the estimated 3-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, progression failure-free survival, and overall survival rates were 92.8%, 92.9%, 89.5%, 78.7%, and 87.5%, respectively. The median cycle for nimotuzumab addition was 6 weeks. Grade 3 radiation-induced mucositis accounted for 36.8% of treated people. No skin rash and infusion reaction were observed, distinctly from what is reported in cetuximab-treated patients. CONCLUSION: Nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities for patients.

14.
Brain Res ; 1624: 78-85, 2015 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-26210618

RESUMO

3-O-demethylswertipunicoside (3-ODS) has been reported to protect dopaminergic neurons against neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP(+)) in PC12 cells. Here, we investigate the neuroprotective effects in vivo and antioxidant activities in vitro of 3-ODS. In the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD), 3-ODS dose-dependently improved motor coordination (as shown by rotarod test), increased the contents of dopamine (DA) and its metabolites in the striatum, and increased the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN). In addition, 3-ODS also increased the spine density in hippocampal CA1 neurons. In antioxidant assays, 3-ODS showed a strong capacity in scavenging hydroxyl radical, superoxide anion and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical in a concentration-dependent manner. Taken together, we conclude that 3-ODS attenuates the PD-related motor deficits mainly through its neuroprotective effects, growth-promoting effects on spine density, and its antioxidant activities.


Assuntos
Glucosídeos/uso terapêutico , Intoxicação por MPTP/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Xantonas/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Compostos de Bifenilo/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Glucosídeos/química , Hipocampo/efeitos dos fármacos , Radical Hidroxila/metabolismo , Técnicas In Vitro , Intoxicação por MPTP/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Picratos/metabolismo , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/patologia , Superóxidos/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Xantonas/química
15.
J Pharmacol Sci ; 125(1): 39-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24739282

RESUMO

Oxidative stress is an important pathophysiological factor of asthma and chronic obstructive pulmonary disease (COPD). We hypothesized that procaterol and dexamethasone might treat inflammation through inhibiting oxidative stress in vitro. This study evaluated procaterol and dexamethasone in the hydrogen peroxide (H2O2)-induced immortal human bronchial epithelial cell model of oxidative stress and investigated the underlying mechanisms. Results showed that exposure to 125 µM H2O2 for 2 h led to a 50% reduction in the cell viability, significantly increased the percentage of apoptosis, and elevated levels of malondialdehyde and reactive oxygen species. Pretreatment with procaterol (25 - 200 nM) could reduce these effects in a dose-dependent manner. In contrast, pretreatment with dexamethasone (100 nM, 1000 nM) was inefficient. Pretreatment with procaterol plus dexamethasone (100 nM procaterol + 1000 nM dexamethasone) was effective, but the combined effect was not more effective than the sole pretreatment with 100 nM procaterol. The nuclear factor kappa-B (NF-κB) pathway was involved in the pathogenic mechanisms of H2O2. Procaterol may indirectly inhibit H2O2-induced activation of the NF-κB pathway due to its capability of antioxidation. Glucocorticoids may be not recommended to treat asthma or COPD complicated with severe oxidative stress.


Assuntos
Antioxidantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Procaterol/farmacologia , Anti-Inflamatórios , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dexametasona/farmacologia , Humanos , Malondialdeído/metabolismo , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Espécies Reativas de Oxigênio/metabolismo
16.
PLoS One ; 9(3): e91362, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24608637

RESUMO

OBJECTIVE: To evaluate the effectiveness and toxicities in T4 nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT) combined with chemotherapy. METHODS: This is a retrospective analysis of 81 patients treated with intensity-modulated radiotherapy (IMRT). All the primary tumors were attributed to T4 stage according to the AJCC2010 staging system. And the distribution of disease by N stage was N0 in 13.6%, N1 in 30.9%, N2 in 37%, and N3 in 18.5%. Cisplatin-based chemotherapy was offered to all patients. Radiotherapy-related toxicities were graded according to the Acute and the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group (RTOG) scoring criteria. Chemotherapy-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Prognostic factors were assessed by univariate analysis. RESULTS: With a median follow-up of 37 months, 12 patients experienced local regional failure and total distant metastasis occurred in 18 patients, representing the major mode of failure. Ten patients died. Among them, 70% died of distant metastasis. The 3-year actuarial rates of local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure-free survival (DFFS), overall survival (OS), and progression-free survival (PFS) were 83.8%, 97.4%, 81.3%, 90%, and 69.7%, respectively. Acute and late toxicities were mild or moderate. CONCLUSIONS: IMRT provides excellent local-regional control for T4 NPC. Distant metastasis remains the major cause of treatment failure. Further explorations of the sequence and regimen of systemic therapy are needed in the future.


Assuntos
Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Idoso , Carcinoma , Criança , Cisplatino/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/tratamento farmacológico , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
17.
Biol Pharm Bull ; 36(8): 1348-55, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23902978

RESUMO

Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.


Assuntos
Antiasmáticos/uso terapêutico , Benzoatos/uso terapêutico , Hiper-Reatividade Brônquica/tratamento farmacológico , Indóis/uso terapêutico , Procaterol/uso terapêutico , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Animais , Antiasmáticos/farmacologia , Benzoatos/farmacologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Indóis/farmacologia , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/patologia , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Cloreto de Metacolina , Camundongos , NF-kappa B/imunologia , Ozônio , Procaterol/farmacologia
18.
Zhongguo Zhong Yao Za Zhi ; 33(7): 822-4, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18589792

RESUMO

OBJECTIVE: To study the analgesic effects and sites of oxymatrine-carbenoxolone sodium complex (OCSC). METHOD: Adopting formalin test, warm water tail-flick test and intracerebroventricularly (icv) injection to observe the analgesic effects of OCSC in mice. RESULT: Intraperitoneally injecting (ip) OCSC (75, 150 mg x kg(-1)) remarkedly inhibited the pain of mice in the formalin test and prolonged latent phases of tail-shrinking of mice, icy OCSC (1.875, 3.75, 7.5 mg x kg(-1)) significantly prolonged latent phases of tail-shrinking of mice, it had dose-dependent effect with concentration. CONCLUSION: The result indicated that OCSC has obvious analgesic effects and its mechanism may be involved in central nervous system (CNS).


Assuntos
Alcaloides/química , Analgésicos/química , Analgésicos/farmacologia , Carbenoxolona/química , Carbenoxolona/farmacologia , Quinolizinas/química , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Animais , Carbenoxolona/administração & dosagem , Carbenoxolona/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Dor/tratamento farmacológico
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