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1.
Clin Cosmet Investig Dermatol ; 16: 1583-1587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37359718

RESUMO

Psoriasis is an immune-mediated chronic inflammatory disease that can be combined with complications such as diabetes, cardiovascular disease, obesity, and kidney disease. The comorbidity of psoriasis with autoimmune bullous diseases (AIBD) has been reported previously in several cases, the most frequent of which is bullous pemphigoid (BP). The underlying mechanisms of psoriasis with BP are not clear and there are no uniform treatment criteria. Based on previous case reports, the coexistence of psoriasis and BP may be related to inflammatory activity, medications, phototherapy, and infection. We report a case of a psoriasis patient who developed BP after taking Chinese herbal compounds and was successfully treated with dupilumab, which is the first reported case of applying dupilumab to treat psoriasis with BP comorbidities.

2.
Ann Palliat Med ; 9(4): 2096-2110, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692227

RESUMO

BACKGROUND: It has been proven that blood stasis plays an important role in the occurrence and development of acute coronary syndrome (ACS) due to Qi-stagnation or Qi-deficiency in traditional Chinese medicine (TCM). However, the diagnosis of Qi-stagnation and blood stasis (QSBS) and Qi-deficiency and blood stasis (QDBS) syndromes mainly depends on the subjective signs or symptoms in clinical practice. Using a combination of TCM and modern medicine, this study aimed to investigate the clinical characteristics of patients with QSBS or QDBS syndromes and to establish a diagnostic prediction model for Qi-blood syndrome differentiation in clinical practice. METHODS: Patients with ACS who were diagnosed with QSBS syndrome or QDBS syndrome and met the inclusion criteria were enrolled. Clinical characteristics, laboratory evaluation, and angiographic characteristics of the two syndrome groups were compared and analyzed. Potential predictive factors associated with QSBS and QDBS syndromes were explored to establish a diagnostic model for syndrome differentiation. RESULTS: A total of 216 participants with ACS, including 108 patients with QSBS syndrome and 108 patients with QDBS syndrome, were enrolled from Beijing Anzhen Hospital Affiliated to Capital Medical University from April 2018 to July 2019. We found that patients with QSBS syndrome were more likely to be males, and have of triple-vessel lesions, relatively high blood stasis syndrome score, normal ejection fraction, and a relatively low-density lipoprotein cholesterol (LDL-C) level. Meanwhile, patients with QDBS syndrome were more likely to have low ejection fraction, high LDL-C level, left main non-triple-vessel lesions, and a relatively low blood stasis syndrome score. The receiver operating characteristic curve and Hosmer-Leme show tests confirmed the discrimination power and reliability of the logistic regression model. CONCLUSIONS: The present study suggested that male sex, the level of LDL-C, ejection fraction, left main lesions, triple-vessel disease, and the score of blood stasis syndrome were the independent predictive factors of Qi-blood syndromes. A good discrimination power of clinical diagnostic prediction model was established using a combination of TCM and modern medicine, and could assist in the differentiation of QSBS syndrome and QDBS syndrome in clinical practice.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Qi , Síndrome Coronariana Aguda/diagnóstico , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Reprodutibilidade dos Testes
3.
Biomed Pharmacother ; 129: 110283, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32531677

RESUMO

BACKGROUND: Shenxiang Suhe Pill (SXSHP), a Chinese medicine formula, is widely used in clinic to treat coronary heart disease (CHD). However, due to the complex composition of SXSHP, its underlying mechanisms and pharmacodynamic properties are still unknown. In this paper, we try to define the compounds of SXSHP by dual-screening the active ingredients with anti-inflammation and antioxidant effects and predict its multi-target-pathway in CHD therapy using network pharmacology. METHODS: The chemical constituents in SXSHP were analyzed by UPLC/Q-TOF. Then, the active ingredients with the anti-inflammation and antioxidant effects were dual-screened by in vitro experiments. Ingenuity pathway analysis (IPA) was used to analyze and predict the potential targets and pathways of the anti-inflammatory and antioxidant effects of SXSHP. RESULTS: A total of 38 chemical constituents were identified in SXSHP, among which we screened six anti-inflammatory compounds: luteolin, isorhamnetin-3-O-beta-d-glucoside, 4-hydroxy-3-methoxycinnamaldehyde, benzoic acid, kaempferol-3-O-glucuronide acid, and blumeatin; and five antioxidant compounds: vanillin, eugenol, muscone, luteolin, and asiatic acid. IPA showed that eugenol, muscone, and 4-hydroxy-3-methoxycinnamaldehyde were closely related to the HIF-1 and IL-15 signaling pathways, which protect against oxidative stress and inflammation, respectively. CONCLUSIONS: Among the 38 ingredients in SXSHP, the anti-inflammatory pharmacological effects of isorhamnetin-3-O-beta-d-glucoside, blumeatin and 4-hydroxy-3-methoxycinnamaldehyde were reported for the first time. According to the network pharmacology analysis, eugenol, 4-hydroxy-3-methoxycinnamaldehyde and muscone are involved in the antioxidant HIF-1 pathway and the anti-inflammatory IL-15 pathway, and that may be the mechanism of SXSHP in the treatment of CHD.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Hipóxia Celular , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Doença das Coronárias/metabolismo , Medicamentos de Ervas Chinesas/química , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Espectrometria de Massas por Ionização por Electrospray
4.
Oxid Med Cell Longev ; 2020: 8683404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566106

RESUMO

Atherosclerosis is a multifactorial vascular disease triggered by disordered lipid metabolism, characterized by chronic inflammatory injury, and initiated by endothelial dysfunction. Berberine is the main active alkaloid of the herbal medicine Coptidis Rhizoma (Huanglian). Notably, berberine has been shown to have beneficial effects against atherosclerosis. However, the mechanisms of berberine in preventing atherosclerosis are still unclear. This study is aimed at investigating the effects and mechanisms of berberine in protecting the aorta and ameliorating atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we demonstrated that berberine reduced serum lipid levels, antagonized hepatic lipid accumulation, improved intima-media thickening, and alleviated atherosclerotic lesions in ApoE-/- mice fed a western-type diet for 12 weeks. Meanwhile, berberine reduced aortic reactive oxygen species (ROS) generation and reduced the serum levels of malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and interleukin-6 (IL-6). In aortic ring assay, berberine restored aortic endothelium-dependent vasodilatation in vivo and in vitro. Furthermore, 4,956 proteins were identified by proteomic analysis, and 199 differentially expressed proteins regulated by berberine were found to be involved in many biological pathways, such as mitochondrial dysfunction, fatty acid ß-oxidation I, and FXR/RXR activation. Summarily, these data suggested that berberine ameliorates endothelial dysfunction and protects against atherosclerosis, and thus may be a promising therapeutic candidate for atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , Berberina/uso terapêutico , Endotélio Vascular/fisiopatologia , Proteômica , Espectrometria de Massas em Tandem , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/fisiopatologia , Apolipoproteínas E/deficiência , Aterosclerose/sangue , Aterosclerose/patologia , Berberina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Ácidos Graxos/sangue , Ontologia Genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Proteoma/metabolismo , Triglicerídeos/sangue
5.
Invest Ophthalmol Vis Sci ; 61(3): 8, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32150250

RESUMO

Purpose: Thymic stromal lymphopoietin (TSLP) is a pro-allergic cytokine that initiates allergic inflammatory reaction between epithelial and dendritic cells (DCs). miR-19b was reported to suppress TSLP expression. The present study aimed to examine miR-19b expression, regulation, and function in allergic conjunctivitis (AC). Methods: A murine model of experimental AC was induced in BALB/c mice by short ragweed pollen. The serum, eye balls, conjunctiva, and cervical lymph nodes (CLN) were used for the study. Gene expression was determined by RT-PCR, whereas protein production and activation were evaluated by immunostaining, ELISA, and Western blotting. Results: In the murine AC model, miR-19b was aberrantly downregulated, whereas the levels of TSLP and p-STAT3, as well as the number of CD11c+ pSTAT3+ DCs were increased. Moreover, Th2 inflammatory cytokine expression was significantly increased. These severe phenotypes could be counteracted by either applying exogenous miR-19b mimic microRNAs or the JAK/STAT inhibitor CYT387. Moreover, overexpression of miR-19b repressed p-STAT3 expression and the number of CD11c+ cells in AC eye and CLN tissues. Conclusions: These findings suggested that miR-19b reduced ocular surface inflammation by inhibiting Stat3 signaling via TSLP downregulation in a murine AC model. Moreover, the present study further demonstrated the clinical potential of applying miR-19b and anti-JAK/STAT therapies in the treatment of AC.


Assuntos
Conjuntivite Alérgica/genética , Janus Quinases/fisiologia , MicroRNAs/genética , Fatores de Transcrição STAT/fisiologia , Animais , Antígenos de Plantas , Antígenos CD11/metabolismo , Vértebras Cervicais , Túnica Conjuntiva/metabolismo , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/metabolismo , Córnea/metabolismo , Citocinas/biossíntese , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Janus Quinases/antagonistas & inibidores , Linfonodos/metabolismo , Camundongos Endogâmicos BALB C , MicroRNAs/biossíntese , Fenótipo , Extratos Vegetais , Fatores de Transcrição STAT/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Linfopoietina do Estroma do Timo
6.
Mol Immunol ; 114: 179-188, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376731

RESUMO

The production of inflammatory cytokines is closely related to pathogen-associated molecular pattern (PAMP)-triggered activation of the Toll-like receptor (TLR), intracellular signal transduction pathways such as MAPK and NF-κB, and histone modifications. Histone methylation, a type of histone modifications, is mainly accomplished by a class of SET family proteins containing highly conserved SET domains. In the present study, we found that SET domain-containing protein 4 (SETD4) regulated inflammatory cytokines in response to TLR agonists. LPS stimulation led to the enhanced SETD4 expression, while the increased IL-6 and TNF-α release from LPS-stimulated RAW264.7 cells was attenuated by depletion of SETD4 using RNA interference. The results were further confirmed in BMDMs and pMφ isolated from SETD4-deficient mice where SETD4-/- macrophages treated with LPS, BLP or Poly(I:C) showed down-regulated IL-6 and TNF-α mRNA and protein levels when compared with SETD4+/+ macrophages. Moreover, the mRNA levels of all NF-κB-dependent genes including IL-1ß, IL-10, NFKBA, DUSP1, CCL2, CCL5, and CXCL10 in SETD4-/- macrophages were substantially reduced. To further clarify the regulatory mechanism(s) by which SETD4 modulates inflammatory cytokines, we examined the effect of SETD4 on the activation of MAPK and NF-κB signalling pathways, and found that knockout of SETD4 had no effect on phosphorylation of p38, ERK, JNK, p65, and IκBα. Notably, SETD4 translocated quickly from the cytosol to the nucleus upon LPS stimulation, suggesting that SETD4 may exert its regulatory function downstream of the MAPK and NF-κB pathways. To characterize this, we performed an in vitro HMTase assay to measure histone methyltransferase (HMTase) activity of SETD4. H3K4me1 and H3K4me2 levels were enhanced dramatically with the supplementation of SETD4, whereas both H3K4me1 and H3K4me2 were strongly attenuated in SETD4-/- BMDMs. Moreover, the LPS-stimulated recruitment of H3K4me1 and H3K4me2 at both TNF-α and IL-6 promoters was severely impaired in SETD4-/- BMDMs. Collectively, these results demonstrate that SETD4 positively regulates IL-6 and TNF-α expression in TLR agonist-stimulated macrophages by directly activating H3K4 methylation.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Citocinas/metabolismo , Lisina/metabolismo , Macrófagos/metabolismo , Metiltransferases/metabolismo , Receptores Toll-Like/metabolismo , Animais , Linhagem Celular , Histonas/metabolismo , Inflamação/metabolismo , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Fosforilação/fisiologia , Regiões Promotoras Genéticas/fisiologia , Células RAW 264.7 , Transdução de Sinais/fisiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-30911318

RESUMO

OBJECTIVE: Danshen, the root of Salvia miltiorrhiza Bunge, is a traditional herbal medicine in China, which has been used to treat irregular menstruation, cold hernia, and abdominal pain for thousands of years. Danshen is frequently used in combination with drugs to treat cardiovascular diseases. Clopidogrel is a commonly used drug for treating coronary heart disease, but clopidogrel resistance restricts its development. Therefore, the clinical efficacy of Danshen combined with clopidogrel treats coronary heart disease and the relationship between Danshen and clopidogrel metabolism enzymes is suggested for future investigations. MATERIALS AND METHODS: The information was collected by searching online databases, and the RevMan 5.3 software was used to perform meta-analysis. RESULTS: Twenty-two articles, including 2587 patients, were enrolled after the evaluation. Meta-analysis showed that Danshen combined with clopidogrel was more effective than clopidogrel alone in treating coronary heart disease by improving clinical curative effect, reducing the frequency of angina pectoris, improving electrocardiogram results, shortening the duration of angina pectoris, and easing adverse reactions. Danshen inhibited carboxylesterase 1 and most enzyme of cytochrome P450, especially cytochrome P450 1A2, which may affect the metabolism of clopidogrel. CONCLUSION: Danshen combined with clopidogrel may compensate for individual differences of clopidogrel resistance among individuals in the treatment of coronary heart disease. Meanwhile, the inhibitory effect of Danshen on cytochrome P450 and carboxylesterase 1 could be partly responsible for the synergistic and attenuating effects of Danshen combined with clopidogrel.

8.
BMC Ophthalmol ; 18(1): 283, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376816

RESUMO

BACKGROUND: Universal ocular screening of infants is not a standard procedure in children's health care system in China. This pilot study investigated prevalence of ocular abnormalities of 6 weeks-age infants using wide-field digital imaging system. METHODS: Infants aged 6 weeks around were consecutively enrolled in a public hospital between April 2015 and August 2016. All the infants who were enrolled in the study underwent vision assessment, eye position examination, external eye check, pupillary light reflex, red reflex examination, anterior and posterior ocular segments were examined using flashlight, ophthalmoscope, and wide-field digital imaging system. RESULTS: A total of 481 infants at 45.1 ± 6.1 days after birth were enrolled in the study. 198 infants had abnormal findings (41.2%). Retinal white spots and retinal white areas were the most common findings (42.9% of abnormalities and 17.7% of all infants screened). The second major finding was retinal hemorrhage (16.2% of abnormalities and 6.7% of all infants screened). Other abnormal findings include retinal pigmentation, concomitant exotropia, neonatal dacryocystitis, retinopathy of prematurity, 'albinism-like fundus', congenital nasolacrimal duct obstruction, familial exudative vitreoretinopathy, immature retina, corneal dermoid tumor, large physiologic cupping of optic disc, congenital persistent pupillary membrane, entropion trichiasis, subconjunctival hemorrhage, congenital cataract, vitreous hemorrhage, ptosis and choroidal nevus. Intervention of any form was required in 22 infants, which accounted for 11.1% of abnormalities detected and 4.6% of all infants screened. CONCLUSION: Universal ocular screening is not only necessary for preterm infants but also for full-term infants. Addition of red reflex examination with wide-field digital imaging system can enhance the sensitivity of screening for ocular fundus abnormities. Further study with a long-term follow-up is needed in the future.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Anormalidades do Olho/epidemiologia , Retina/diagnóstico por imagem , Seleção Visual/métodos , China/epidemiologia , Anormalidades do Olho/diagnóstico , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Prevalência , Retina/anormalidades , Estudos Retrospectivos
9.
Front Med ; 12(1): 92-97, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29288283

RESUMO

Investigations on the genetic diversity of Mycobacterium tuberculosis in China have shown that Beijing genotype strains play a dominant role. To study the association between the M. tuberculosis Beijing genotype and the drug-resistance phenotype, 1286 M. tuberculosis clinical isolates together with epidemiological and clinical information of patients were collected from the center for tuberculosis (TB) prevention and control or TB hospitals in Beijing municipality and nine provinces or autonomous regions in China. Drug resistance testing was conducted on all the isolates to the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin, and ethambutol). A total of 585 strains were found to be resistant to at least one of the four anti-TB drugs. The Beijing family strains consisted of 499 (53.20%) drug-sensitive strains and 439 (46.80%) drug-resistant strains, whereas the non-Beijing family strains comprised 202 (58.05%) drug-sensitive strains and 146 (41.95%) drug-resistant strains. No significant difference was observed in prevalence (χ2= 2.41, P > 0.05) between the drug-resistant and drugsensitive strains among the Beijing family strains. Analysis of monoresistance, multidrug-resistant TB, and geographic distribution of drug resistance did not find any relationships between the M. tuberculosis Beijing genotype and drug-resistance phenotype in China. Results confirmed that the Beijing genotype, the predominant M. tuberculosis genotype in China, was not associated with drug resistance.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , China/epidemiologia , Variação Genética , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo
10.
Chin J Integr Med ; 23(11): 845-849, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28028722

RESUMO

OBJECTIVE: To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS). METHODS: Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2). RESULTS: Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05). CONCLUSIONS: Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.


Assuntos
Síndrome Coronariana Aguda/sangue , Inflamação/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Síndrome
11.
Enzyme Microb Technol ; 95: 185-191, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27866614

RESUMO

Nano-selenium has a great potential to be used in chemical, biological, medical and environmental fields. Biological methods for nano-selenium synthesis have attracted wide interests, because they can be operated at ambient temperature and pressure without complicated equipments. In this work, a protozoa, Tetrahymena thermophila (T. thermophila) SB210, was used to in vivo synthesize nano-selenium. The biosynthesized nano-selenium was characterized using transmission electron microscopy, energy dispersive X-ray spectroscopy and Raman spectroscopy. The synthesized amorphous spherical selenium nanoparticles had diameters of 50-500nm with the coexistence of irregular nano-selenium. The expressions of glutathione (GSH) synthesis related gene glutathione synthase, cysteine-rich protein metallothionein related gene metallothionein-1 and [2Fe-2S] cluster-binding protein related gene were up-regulated in the nano-selenium producing group. Also, the subsequent GSH detection and in vitro synthesis experimental results suggest the three proteins were likely to be involved in the nano-selenium synthesis process.


Assuntos
Nanopartículas Metálicas/química , Selênio/química , Tetrahymena thermophila/metabolismo , Biotecnologia , Genes de Protozoários , Glutationa/metabolismo , Glutationa Sintase/genética , Glutationa Sintase/metabolismo , Química Verde , Nanopartículas Metálicas/ultraestrutura , Nanotecnologia , Oxirredução , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Ácido Selenioso/metabolismo , Tetrahymena thermophila/genética
12.
Oncotarget ; 7(27): 41274-41284, 2016 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-27129180

RESUMO

Sorafenib is a multikinase inhibitor approved as the first line treatment for late stage hepatocellular carcinoma (HCC). Due to its significant variation in clinical benefits among patients, defining prognostic biomarkers for sorafenib sensitivity in HCC would allow targeted treatment. Phosphorylated extracellular signaling-regulated kinase (pERK) was proposed to predict the response to sorafenib in HCC, but clinical supports are mixed or even contradictory. Here we found that pERK expression levels are variable in different nodules from individual patient liver. Xenografts derived from resected tumors are resistant to sorafenib inhibition when expressing low levels of pERK. This correlation of low pERK levels and sorafenib resistance is corroborated by histological characterization of chemical-induced and genetic mouse models for pERK-positive and pERK-negative HCC respectively, as well as computed tomography (CT) imaging of patient tumors with validated pERK expression. Mouse and human HCC samples expressing low pERK show strong inflammatory infiltrating cells and significant enrichment of intratumoral CD8+ cytotoxic T lymphocytes that express programmed death receptor-1 (PD-1). These pERK-PD-1+ patients have poorer overall and disease-free survival than pERK+PD-1- patients. In conclusion, our data suggest that anti-PD-1 immunotherapy might complement sorafenib in treating HCC patients by targeting sorafenib-resistant cancer cells, and the dual pERK and PD-1 biomarkers would help HCC patient selection to achieve optimal clinical benefits.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Células K562 , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Camundongos Transgênicos , Niacinamida/uso terapêutico , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sorafenibe
13.
BMC Complement Altern Med ; 15: 279, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26271359

RESUMO

BACKGROUND: Gastrointestinal microbial communities are diverse and are composed of both beneficial and pathogenic groups. Prebiotics, such as digestion-resistant fibers, influence the composition of gut microbiota, and can contribute to the improvement of host health. The red seaweed Chondrus crispus is rich in dietary fiber and oligosaccharides, however its prebiotic potential has not been studied to date. METHODS: Prebiotic effects were investigated with weaning rats fed a cultivated C. crispus-supplemented diet. Comparison standards included a fructo-oligo-saccharide (FOS) diet and a basal diet. The colonic microbiome was profiled with a 16S rRNA sequencing-based Phylochip array. Concentrations of short chain fatty acids (SCFAs) in the feacal samples were determined by gas chromatography with a flame ionization detector (GC-FID) analysis. Immunoglobulin levels in the blood plasma were analyzed with an enzyme-linked immunosorbent assay (ELISA). Histo-morphological parameters of the proximal colon tissue were characterized by hematoxylin and eosin (H&E) staining. RESULTS: Phylochip array analysis indicated differing microbiome composition among the diet-supplemented and the control groups, with the C. crispus group (2.5% supplementation) showing larger separation from the control than other treatment groups. In the 2.5% C. crispus group, the population of beneficial bacteria such as Bifidobacterium breve increased (4.9-fold, p=0.001), and the abundance of pathogenic species such as Clostridium septicum and Streptococcus pneumonia decreased. Higher concentrations of short chain fatty acids (i.e., gut microbial metabolites), including acetic, propionic and butyric acids, were found in faecal samples of the C. crispus-fed rats. Furthermore, both C. crispus and FOS supplemented rats showed significant improvements in proximal colon histo-morphology. Higher faecal moisture was noted in the 2.5% C. crispus group, and elevated plasma immunoglobulin (IgA and IgG) levels were observed in the 0.5% C. crispus group, as compared to the basal feed group. CONCLUSIONS: The results suggest multiple prebiotic effects, such as influencing the composition of gut microbial communities, improvement of gut health and immune modulation in rats supplemented with cultivated C. crispus.


Assuntos
Bactérias/efeitos dos fármacos , Chondrus/química , Colo/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Imunoglobulinas/sangue , Oligossacarídeos/farmacologia , Prebióticos , Animais , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Colo/metabolismo , Colo/microbiologia , Fibras na Dieta/farmacologia , Suplementos Nutricionais , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Masculino , RNA Ribossômico 16S/genética , Ratos Sprague-Dawley , Alga Marinha
14.
Cancer Lett ; 367(1): 1-11, 2015 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-26170167

RESUMO

Sorafenib, an orally-available kinase inhibitor, is the only standard clinical treatment against advanced hepatocellular carcinoma. However, development of resistance to sorafenib has raised concern in recent years due to the high-level heterogeneity of individual response to sorafenib treatment. The resistance mechanism underlying the impaired sensitivity to sorafenib is still elusive though some researchers have made great efforts. Here, we provide a systemic insight into the potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma depending on abundant previous studies and reports.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Niacinamida/uso terapêutico , Sorafenibe
15.
Mar Drugs ; 13(4): 2250-66, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25874922

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the elderly people, currently with no cure. Its mechanisms are not well understood, thus studies targeting cause-directed therapy or prevention are needed. This study uses the transgenic Caenorhabditis elegans PD model. We demonstrated that dietary supplementation of the worms with an extract from the cultivated red seaweed Chondrus crispus decreased the accumulation of α-synulein and protected the worms from the neuronal toxin-, 6-OHDA, induced dopaminergic neurodegeneration. These effects were associated with a corrected slowness of movement. We also showed that the enhancement of oxidative stress tolerance and an up-regulation of the stress response genes, sod-3 and skn-1, may have served as the molecular mechanism for the C. crispus-extract-mediated protection against PD pathology. Altogether, apart from its potential as a functional food, the tested red seaweed, C. crispus, might find promising pharmaceutical applications for the development of potential novel anti-neurodegenerative drugs for humans.


Assuntos
Chondrus/química , Suplementos Nutricionais , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/dietoterapia , Extratos Vegetais/uso terapêutico , Alga Marinha/química , alfa-Sinucleína/antagonistas & inibidores , Animais , Animais Geneticamente Modificados , Aquicultura , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Comportamento Animal/efeitos dos fármacos , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/agonistas , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Chondrus/crescimento & desenvolvimento , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia de Fluorescência , Movimento/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Neurotoxinas/antagonistas & inibidores , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Extratos Vegetais/administração & dosagem , Proteínas Recombinantes de Fusão/metabolismo , Alga Marinha/crescimento & desenvolvimento , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
16.
Zhonghua Gan Zang Bing Za Zhi ; 23(1): 46-9, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25751386

RESUMO

OBJECTIVE: To observe liver cirrhosis with esophageal and gastric variceal bleeding (GEVB) after endoscopic variceal ligation and treatment of early oral nutrition liquid in patients administered to reduce the risk of early rebleeding. METHODS: Seventy-eight patients with cirrhosis who received therapeutic endoscopy after GEVB and who suffered from malnutrition were randomly divided into a treatment group (oral solution group, n=40) and a control group (regular diet group, n=38).Both of the two groups received food at 12 hours after therapeutic endoscopy.After 14 days, the rates of early rebleeding rate and liver function recovery were compared for the two groups. T-test, rank test, chi-square test and Fisher's exact test were used for statistical analyses. RESULTS: Compared with the control group, less patients in the treatment group experienced rebleeding (0/40 vs. 5/38; x2=5.624, P=0.018); the treatment group also showed significantly improved indexes of liver function (all P less than 0.05). CONCLUSION: s GEVB after endoscopic treatment with early oral nutrition liquid administration can reduce in the early rebleeding risk and improve function and malnutrition status.


Assuntos
Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Endoscopia Gastrointestinal , Humanos , Ligadura , Cirrose Hepática , Recidiva , Resultado do Tratamento
17.
Appl Environ Microbiol ; 79(23): 7343-50, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24056462

RESUMO

Marine macroalgae are rich in bioactive compounds that can, when consumed, impart beneficial effects on animal and human health. The red seaweed Chondrus crispus has been reported to have a wide range of health-promoting activities, such as antitumor and antiviral activities. Using a Caenorhabditis elegans infection model, we show that C. crispus water extract (CCWE) enhances host immunity and suppresses the expression of quorum sensing (QS) and the virulence factors of Pseudomonas aeruginosa (strain PA14). Supplementation of nematode growth medium with CCWE induced the expression of C. elegans innate immune genes, such as irg-1, irg-2, F49F1.6, hsf-1, K05D8.5, F56D6.2, C29F3.7, F28D1.3, F38A1.5 ZK6.7, lys-1, spp-1, and abf-1, by more than 2-fold, while T20G5.7 was not affected. Additionally, CCWE suppressed the expression of PA14 QS genes and virulence factors, although it did not affect the growth of the bacteria. These effects correlated with a 28% reduction in the PA14-inflicted killing of C. elegans. Kappa-carrageenan (K-CGN), a major component of CCWE, was shown to play an important role in the enhancement of host immunity. Using C. elegans mutants, we identified that pmk-1, daf-2/daf-16, and skn-1 are essential in the K-CGN-induced host immune response. In view of the conservation of innate immune pathways between C. elegans and humans, the results of this study suggest that water-soluble components of C. crispus may also play a health-promoting role in higher animals and humans.


Assuntos
Antibacterianos/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/microbiologia , Chondrus/química , Fatores Imunológicos/metabolismo , Extratos Vegetais/metabolismo , Pseudomonas aeruginosa/imunologia , Animais , Antibacterianos/isolamento & purificação , Caenorhabditis elegans/imunologia , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/isolamento & purificação , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Receptor de Insulina/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Virulência/biossíntese
18.
Zhongguo Zhong Yao Za Zhi ; 30(13): 1001-5, 2005 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16161429

RESUMO

OBJECTIVE: To study the effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption for analyzing its underlying mechanism in the treatment of coronary heart disease. METHOD: A total of 20 dogs anesthetized with pentobarbital sodium (30 mg x kg(-1), i.v.) were evenly randomized into control group, low-dose Gadol (LDG) group, high-dose Gadol (HDG) group and Herbesser Injection group. The blood flow volume (BFV) of the left coronary artery and cardiac output (CO), left ventricular pressure (LVP), maximum ascending rate (dp/dtmax) of LVP, mean arterial pressure (MAP) of the femoral artery, oxygen contents of the coronary artery and coronary vein (venous sinus), oxygen consumption index (OCI), cardiac index (CI), coronary artery resistance (CAR) and total peripheral resistance (TPR) as well as oxygen utilization rate (OUR) were detected respectively. RESULT: After venous injection of Gadol, CAR, MAP, TPR, OCI, myocardial oxygen consumption and heart rate lowered significantly (P < 0.05-0.01), while BFV and blood oxygen content of the venous sinus increased considerably (P < 0.05-0.01) in comparison with pre-injection. No significant differences were found in LVP and myocardial contractivity between control group and LDG, and between control and HDG groups respectively. CONCLUSION: It showed dilation of the coronary artery and reduction of the cardiac afterload after injection of Gadol. Besides, CO and stroke volume increased considerably and the cardiac effective work was raised without any significant simultaneous increase of both myocardial contractility and LVP. A decrease in the myocardial oxygen consumption and reduction of OCI indicates an improvement of the oxygen supply of the myocardium, and a favorable regulation of the compliance of the cardiac vessels. As a result, the cardiovascular performance was ameliorated. The abovementioned improvement of these indexes may contribute to the therapeutic effect of Gadol in the treatment of coronary heart disease in clinic.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hemodinâmica/efeitos dos fármacos , Miocárdio/metabolismo , Rhodiola , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Cães , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Masculino , Oxigênio/metabolismo , Plantas Medicinais/química , Distribuição Aleatória , Rhodiola/química , Resistência Vascular/efeitos dos fármacos
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