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1.
J Ethnopharmacol ; 264: 113021, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479885

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is an outcome of many chronic liver diseases and often results in cirrhosis, liver failure, and even hepatocarcinoma. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to liver fibrosis in clinical practice while its mechanism is unclear. AIM OF THE STUDY: The aim of this study was to investigate the anti-fibrosis effect of XYS and to explore the molecular mechanisms by combining network pharmacology and transcriptomic technologies. MATERIALS AND METHODS: The carbon tetrachloride (CCl4)-induced liver fibrosis rat were treated with three doses of XYS. The liver fibrosis and function were evaluated by histopathological examination and serum biochemical detection. The fibrosis related protein a-SMA and collagen I were assessed by Western blot. Different expressed genes (DEGs) between XYS-treated group and model group were analyzed. The herb-component-target network was constructed combined the network pharmacology. The predict targets and pathways were validated by in vitro and in vivo experiments. RESULTS: With XYS treatment, the liver function was significantly improved, and fibrotic changes were alleviated. The a-SMA and collagen I expression levels in the liver were also decreased in XYS-treated rats compared with CCl4 model rats. 108 active components and 42 targets from 8 herbs constituted herb-compound-target network by transcriptomics and network pharmacology analysis. The KEGG pathway and GO enrichment analyses showed that the FoxO, TGFß, AMPK, MAPK, PPAR, and hepatitis B and C pathways were involved in the anti-fibrosis effects of XYS. In the liver tissues, p-FoxO3a and p-Akt expression levels were significantly increased in the CCl4 model group but decreased in the XYS-treated group. The TGFß1/Smad pathway and Akt/FoxO3 pathway were verified in LX2 cells by inhibiting phosphorylation of Smad3 and Akt activity, respectively. CONCLUSIONS: Our findings suggested that XYS markedly alleviated CCl4-induced liver fibrosis in histopathological and serum liver function analyses, and this effect may occur via the TGFß1/Smad and Akt/FoxO signaling pathways.

2.
Pharm Biol ; 58(1): 979-991, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32962483

RESUMO

CONTEXT: Yinhuapinggan granule (YHPG) is frequently used for treating fever, cough, and viral pneumonia in traditional Chinese medicine. OBJECTIVE: This study investigated the antiviral effects of YHPG in H1N1 influenza virus (IFV)-infected mice and its possible mechanism. MATERIALS AND METHODS: ICR mice were intranasally infected with 10 LD50 viral dose of IFV and then oral administration of YHPG (6, 12, and 18 g/kg) or oseltamivir (positive control) once a day for 2 or 4 consecutive days, six mice in each group. The lung, spleen and thymus indexes of IFV-infected mice, the expression of viral loads and pathological changes in lung tissues were performed to evaluate the antiviral effects of YHPG. Real-time PCR, immunohistochemistry and western blot assays were used to determine the expression of Bax, Bcl-2 and caspase-3. RESULTS: LD50 in mice was 10-3.5/0.02 mL. YHPG (6, 12, and 18 g/kg) dose-dependently decreased the lung index and viral load; the inhibition ratio of lung index was 5.31, 18.22, and 34.06%, respectively. Further detection revealed that YHPG (12 and 18 g/kg) significantly attenuated lung pathological changes, and increased the spleen and thymus indexes. Moreover, YHPG significantly down-regulated the mRNA and protein expression of Bax and caspase-3 in lung tissues of mice infected with IFV, and up-regulated the expression of Bcl-2. CONCLUSIONS: YHPG has significant antiviral effects in IFV-infected mice, partially by inhibiting influenza virus replication and regulating the occurrence of apoptosis induced by influenza virus infection, suggesting that YHPG may be a promising antiviral agent with potential clinical application prospects.

3.
Aging (Albany NY) ; 12(14): 14949-14965, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32701483

RESUMO

Hepatitis B virus (HBV) infection is an important factor causing hepatocellular carcinoma (HCC). The aim of this study was to investigate the metabolic characteristics and related metabolic enzyme changes during the progression from chronic hepatitis B (CHB) to liver cirrhosis (LC) and, ultimately, to HCC. An untargeted metabolomics assay was performed in plasma from 50 healthy volunteers, 43 CHB patients, 67 LC patients, and 39 HCC patients. A total of 24 differential metabolites (DMs) were identified. Joint pathway analysis suggested striking changes in amino acid metabolism and lipid metabolism from CHB to HCC. The panel of L-serine, creatine and glycine distinguished LC from CHB, and L-serine, cystathionine, creatine and linoleic acid distinguished HCC from LC. Bioinformatic analysis of publicly available data showed that differential metabolite profile-associated enzyme genes, including alanine-glyoxylate aminotransferase-2 (AGXT2), D-amino-acid oxidase (DAO), and cystathionine gamma-lyase (CTH), were downregulated, while bisphosphoglycerate mutase (BPGM), cystathionine-ß-synthase (CBS), phosphoserine phosphatase (PSPH) and acyl-CoA thioesterase 7 (ACOT7) were upregulated, in HCC, all of which correlated with a poor prognosis for HCC patients. Our results indicated that serum metabolites and related enzymes are of considerable significance for the diagnosis and prognosis of HCC and can provide a theoretical basis and therapeutic index for future diagnosis and treatment.

4.
Sci Rep ; 10(1): 3963, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127629

RESUMO

The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing ("meta-transcriptomics") to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence and abundance of viral, bacterial, and eukaryotic pathogens, and to reveal mixed infections, pathogen genotypes/subtypes, evolutionary origins, epidemiological history, and antimicrobial resistance. We identified 11 RNA viruses, 4 DNA viruses, 4 species of bacteria, and 1 fungus. While most are known to cause ARIs, others, such as echovirus 6, are rarely associated with respiratory disease. Co-infection of viruses and bacteria and of multiple viruses were commonplace (9/48), with one patient harboring 5 different pathogens, and genome sequence data revealed large intra-species diversity. Expressed resistance against eight classes of antibiotic was detected, with those for MLS, Bla, Tet, Phe at relatively high abundance. In summary, we used a simple total RNA sequencing approach to reveal the complex polymicrobial infectome in ARI. This provided comprehensive and clinically informative information relevant to understanding respiratory disease.


Assuntos
Metagenoma/genética , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Bactérias/classificação , Bactérias/genética , Bactérias/patogenicidade , Vírus de DNA/classificação , Vírus de DNA/genética , Vírus de DNA/patogenicidade , Resistência Microbiana a Medicamentos/genética , Feminino , Fungos/classificação , Fungos/genética , Fungos/patogenicidade , Humanos , Masculino , Filogenia , Vírus de RNA/classificação , Vírus de RNA/genética , Vírus de RNA/patogenicidade , Vírus/classificação , Vírus/genética , Vírus/patogenicidade
5.
Virol Sin ; 34(5): 489-500, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31161555

RESUMO

The study was conducted to explore the mechanisms of sex differences in the response to chronic hepatitis B (CHB) in terms of DNA methylation, SNP genotype, and gene expression. Genomic DNA was isolated from peripheral blood mononuclear cells (PBMCs) of CHB patients and healthy controls and evaluated using the Human Methylation 450 K Assay. The DNA methylation level at hg37 chromosome (CHR) X: 7810800 was further validated using pyrosequencing. SNP genotypes, VCX mRNA expression of PBMCs, and plasma VCX protein concentration were further examined using SNaPshot, RT-qPCR, and Western blot, respectively. Results showed that a total of 5529 CpG loci were differentially methylated between male and female CHB patients. DNA methylation level and CC + CT frequency at CHR X: 7810800, VCX mRNA expression of PBMCs, and plasma VCX protein concentration were higher in female than in male CHB patients. The CHR X: 7810800 locus was hypermethylated in CHB patients with CC + CT genotypes in comparison with those with the TT genotype. In cases of CC + CT genotypes, VCX mRNA expression was negatively correlated with the DNA methylation level. CHB patients with higher levels of HBV DNA, AST, and GGT or higher GPRI scores exhibited lower VCX expression. In conclusion, SNPs and DNA methylation at the CHR X: 7810800 locus cooperatively regulate VCX expression in CHB. The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis, as observed in male CHB patients.


Assuntos
Metilação de DNA , Hepatite B Crônica/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Adulto , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/sangue , Regiões Promotoras Genéticas , Regulação para Cima , Adulto Jovem
6.
Molecules ; 24(6)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901941

RESUMO

Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-ß1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-ß1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model.


Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Resveratrol/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Metaloproteinases da Matriz/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Biosci Rep ; 39(1)2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30446524

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most fatal types of cancer with significant mortality and morbidity worldwide. MicroRNAs (miRs) have been confirmed to have positive functions in NSCLC. In the present study, we try to explore the role of miR-758 in proliferation, migration, invasion, and apoptosis of NSCLC cells by regulating high-mobility group box (HMGB) 3 (HMGB3.) NSCLC and adjacent tissues were collected. Reverse transcription quantitative PCR (RT-qPCR) was employed to detect expression of miR-758 and HMGB3 in NSCLC and adjacent tissues, in BEAS-2B cells and NSCLC cell lines. The targetted relationship between miR-758 and HMGB3 was identified by dual luciferase reporter gene assay. The effects of miR-758 on proliferation, migration, invasion, cell cycle, and apoptosis of A549 cells. MiR-758 expression was lower in NSCLC tissues, which was opposite to HMGB3 expression. The results also demonstrated that miR-758 can target HMGB3. The cells transfected with miR-758 mimic had decreased HMGB3 expression, proliferation, migration, and invasion, with more arrested cells in G1 phase and increased apoptosis. Our results supported that the overexpression of miR-758 inhibits proliferation, migration, and invasion, and promotes apoptosis of NSCLC cells by negative regulating HMGB2. The present study may provide a novel target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteína HMGB3/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Células A549 , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGB3/metabolismo , Humanos , Neoplasias Pulmonares/genética
8.
Virus Res ; 255: 117-126, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30030018

RESUMO

Enterovirus 71 (EV71) is one of the major pathogens causing hand, foot, and mouth disease (HFMD) with neurological and systemic complications worldwide, and it is mostly discovered in infants and young children. It is of great significance to establish suitable animal models of EV71 infection on research of distribution and pathogenesis of the virus. In this study, we established a successful infection of a non-mouse-adapted isolate of EV71 via oral route in 7-day-old Mongolian gerbil (Meriones unguiculatus), all of which were paralyzed and died within 10 days post infection. Analysis of virus loads in twelve tissues showed that virus was first detected in intestine, blood, heart, lung, and muscle one day post-infection, and then in the rest of the tissues/organs within the next few days, among which thymus, spleen, spinal cord and muscles had the highest virus titer at 5 days post infection. Pathological examination showed that severe necrosis was observed in skeletal muscle and spinal cord, and edema was observed in both heart and lung. Comparisons of host gene expression of various tissues from infected and non-infected gerbils revealed a general up-regulation of genes related to anti-viral response and a viral receptor gene (sialic acid-linked glycans), as well as a tissue(gut)-specific up-regulation of genes related to neuronal communication. Collectively, our results showed that EV71 could induce severe neurological complications as well as massive tissue damage all over the body, which indicates that oral infection of 7-day gerbils can be a suitable animal model to study the infection of EV71 in human.


Assuntos
Modelos Animais de Doenças , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/virologia , Animais , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/genética , Infecções por Enterovirus/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Gerbillinae , Interações Hospedeiro-Patógeno/genética , Análise de Sobrevida , Carga Viral
9.
Zhongguo Zhong Yao Za Zhi ; 43(5): 1028-1033, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29676104

RESUMO

This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice in vivo, in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus in vivo. The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Animais , Vírus da Influenza A Subtipo H1N1 , Sistema de Sinalização das MAP Quinases , Glicoproteínas de Membrana/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 3 Toll-Like/metabolismo , Receptor 7 Toll-Like/metabolismo
10.
Zhongguo Zhong Yao Za Zhi ; 43(3): 563-570, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29600623

RESUMO

To study the effect and underlying mechanism of Mahuang Tang against influenza A virus in vitro, the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID50) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods, and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER), median efficacious concentration(EC50) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4, TLR7, MyD88 and TRAF6 in MDCK cells at 24, 48 h after the treatment. The experiment results indicated that TCID50 of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC50 values of two different treatment methods were 4.92,1.59 g·L⁻¹ respectively, the TI values were 12.53, 38.78 respectively, and when the concentration of Mahuang Tang was 5.00 g·L⁻¹ï¼Œ ER values were 50.21%, 98.41% respectively, showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile, as compared with the virus group, the virus load was significantly inhibited in Mahuang Tang groups, and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4, TLR7,MyD88 and TRAF6 at 24, 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Infecções por Orthomyxoviridae , Animais , Cães , Vírus da Influenza A Subtipo H1N1/fisiologia , Células Madin Darby de Rim Canino , Receptor 4 Toll-Like/metabolismo , Receptor 7 Toll-Like/metabolismo , Replicação Viral/efeitos dos fármacos
11.
Inflammopharmacology ; 26(6): 1455-1467, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29502306

RESUMO

Yinhuapinggan granule (YHPG), a modified prescription based on Ma-Huang-Tang (MHT), is used in traditional Chinese medicine (TCM) to treat influenza, cough, and viral pneumonia. In this study, we investigated the antiviral effects of YHPG by means of pre-, post-, and co-treatment, and its underlying mechanisms on regulating the levels of inflammatory-related cytokines, modulating the mRNA expressions of interferon-stimulated genes in influenza virus-infected murine macrophage cells (RAW264.7), and evaluating the protein expressions of key effectors in the Type I IFN and pattern recognition receptor (PRRs) signaling pathways. The results showed that YHPG markedly inhibited influenza virus (IFV) replication in pre-, post- and co-treatment assay, especially in post-treatment assay. Antiviral mechanisms studies revealed that YHPG (500 and 250 µg/mL) significantly up-regulated levels of IFN-ß, IFN-stimulated genes (Mx-1, ISG-15 and ISG-56) compared with the IFV control group, while the levels of IL-6 and TNF-α were significantly down-regulated. Furthermore, western blot analysis results revealed that the protein expressions of the phosphorylated forms of TBK1, IRF3, ERK1/2, P38 MAPK and NF-κB p65 were significantly down-regulated in RAW264.7 cells with the YHPG (500 and 250 µg/mL) treatment, while the expression of the phosphorylated form of STAT1 was significantly enhanced. Based on these results, YHPG had antiviral effects in IFV-infected RAW264.7 cells, which might be associated with regulation of the inflammatory cytokines production, evaluation of the levels of IFN-stimulated genes, and modulation of the protein expressions of key effectors in the Type I IFN and PRRs signaling pathways.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Interferons/farmacologia , Camundongos , Células RAW 264.7 , RNA Viral/antagonistas & inibidores , RNA Viral/biossíntese , Transdução de Sinais/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
12.
Oncotarget ; 9(1): 1075-1090, 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-29416678

RESUMO

Circulating microRNAs (miRNAs) can be employed as biomarkers to diagnose liver and other diseases. Noninvasive approaches are needed to complement and improve the current strategies for screening for biomarkers liver cirrhosis. We determined whether the serum levels of miRNAs can distinguish between chronic hepatitis B (CHB) and CHB-induced cirrhosis (HBC) and investigated the potential mechanisms involved. We found that serum miR-27a was significantly up-regulated in HBC, distinguishing HBC from CHB and healthy controls (Ctrl) (P<0.0001, the area of under the curve (AUC) =0.82 and 0.87, respectively). Specifically, when miR-27a was combined with miR-122, HBC was differentiated from CHB with an AUC=0.94. The serum miR-27a level in HBC patients with hepatic decompensation was significantly higher than that in patients with compensated HBC (P=0.0009). MiR-27a was also significantly up-regulated in the serum of rats with DMN-induced liver cirrhosis compared to that in saline-treated rats (P<0.0001). Furthermore, the down-regulation of miR-27a inhibited the proliferation and overexpression of miR-27a in activated hepatic stellate cells (HSCs) through the up-regulation of α-SMA and COL1A2 expression by targeting PPARγ, FOXO1, APC, P53 and RXRα. Our study demonstrated that circulating miR-27a can be used as a predictor for the activation of HSCs and the occurrence and development of HBC.

13.
Acta Pharmacol Sin ; 39(6): 942-951, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29072258

RESUMO

Fuzheng-Huayu formula (FZHY), a Chinese herbal mixture prescription, has been proven effective in treating liver fibrosis and cirrhosis in both clinical trials and animal experiments. In this study we assessed the metabolic mechanisms of traditional Chinese medicine (TCM) syndrome-based FZHY treatment in liver cirrhosis (LC). A total of 113 participants, including 50 healthy controls and 63 LC patients, were recruited. According to the diagnosis and differentiation of the TCM syndromes, the LC patients were classified into 5 TCM syndrome groups including the liver stagnation syndrome (LSS), spleen deficiency and damp overabundance syndrome (SDDOS), damp-heat accumulation syndrome (DHAS), liver-kidney Yin deficiency syndrome (LKYDS), and blood stagnation syndrome (BSS), and administered FZHY for 6 months. FZHY treatment significantly decreased serum levels of hyaluronic acid (HA), a biochemical marker for LC, as well as TCM syndrome scores (the TCM syndrome scores were decreased in all the groups with significant decreases in the LSS and LKYDS groups). Furthermore, FZHY treatment gradually shifted the metabolic profiles of LC patients from a pathologic state to a healthy state, especially in LC patients with LSS and LKYDS. Twenty-two differently altered metabolites (DAMs) were identified, including carbohydrates, amino acids, fatty acids, etc with 9 DAMs in LSS patients, 9 in LKYDS patients, and 4 in other patients. The metabolic pathways involved in the conversion of amino acids and the body's detoxification process were regulated first, followed by the pathways involved in the body's energy supply process. In conclusion, the evaluation of the effect of TCM syndrome-based FZHY treatment show that FZHY has a better effect on LKYDS and LSS than on the other TCM syndromes, and the metabolic mechanisms might be involved in the increased detoxification function in LKYDS and the improvement of energy supply in LSS, which provides important evidence for the clinical application of TCM syndrome-based treatment.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Metabolômica/métodos , Biomarcadores/sangue , Estudos de Casos e Controles , China , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Fatores de Tempo , Resultado do Tratamento
14.
Anticancer Res ; 37(11): 6141-6151, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29061795

RESUMO

BACKGROUND/AIM: The synergistic combinations of natural products have long been the basis of Traditional Chinese herbal Medicine formulas. In this study, we investigated the synergistic effects of a combination of berberine and evodiamine against human breast cancer MCF-7 cells in vitro and in vivo, and explored its mechanism. MATERIALS AND METHODS: Cell survival was measured using the MTT assay. Apoptosis-related proteins were observed using western blot analysis. Apoptosis was detected with flow cytometric analysis and by Hoechst 33258 staining. Tumor xenografts were used in vivo. RESULTS: Compared to berberine or evodiamine treatments alone, the combination treatment of berberine (25 µM) and evodiamine (15 µM) synergistically inhibited the proliferation of MCF-7 cells in a time-dependent manner and resulted in the G0/G1 phase accumulation of cells that exhibited increased expression levels of the CDK inhibitors p21 and p27 with a concomitant reduction in the expression levels of cell-cycle checkpoint proteins cyclin D1, cyclin E, CDK4, and CDK6. Furthermore, the combination treatment induced apoptosis that was accompanied by increased expression levels of p53 and Bax, reduced expression levels of Bcl-2, activation of caspase-7, and caspase-9, and the cleavage of PARP. The combination of berberine and evodiamine synergistically inhibited tumor growth in vivo in MCF-7 human breast cancer xenografts. CONCLUSION: Combination of berberine and evodiamine acts synergistically to suppress the proliferation of MCF-7 cells by inducing cell cycle arrest and apoptosis, illustrating the potential synergistic and combinatorial application of bioactive natural products.


Assuntos
Apoptose/efeitos dos fármacos , Berberina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinazolinas/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/metabolismo , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Cancer Cell Int ; 17: 84, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28959140

RESUMO

BACKGROUND: Curcumin, a natural compound derived from the turmeric rhizome Curcuma longa Linn, has anticancer and chemoresistance reduction biological activities. We evaluated the efficacy of curcumin in sensitizing chemotherapy drugs through regulation of Bcl-2-mediated apoptosis in breast cancer stem-like cells (BCSCs). METHODS: Cell survival was measured using MTT assay. Apoptosis-related proteins were observed using western blot analysis. Apoptosis was detected with flow cytometric analysis and by Hoechst 33258 staining. The mitochondrial membrane potential was observed with flow cytometric analysis. RESULTS: The ability of BCSCs to propagate decreased gradually along the passages and was completely lost at the fifth passage [0.1 µmol/L mitomycin C (MMC) with 5 µmol/L curcumin in MCF-7 and 0.5 µmol/L MMC with 5 µmol/L curcumin in MDA-MB-231 cells]. Curcumin combined with MMC treatment significantly decreased the levels of antiapoptotic Bcl-2 and Bcl-w expression, increased the levels of proapoptotic Bax, Bak, Bad, Bik, and Bim expression, and activated caspase-3 and caspase-9 in MCF-7 BCSCs. In the presence of Bcl-2 siRNA, the apoptosis rate increased by 15% in cells treated with curcumin and MMC. The mitochondrial membrane potential decreased by approximately 20% in MCF-7 BCSCs undergoing the combination treatment of curcumin and MMC. The combination-induced decrease in Bcl-2 was regulated by the presence of the Wnt-specific inhibitor PFK115-584 and PI3k inhibitor LY294002. CONCLUSIONS: Our study indicates that curcumin might represent a novel therapeutic agent for treating breast cancer chemoresistance induced by MMC.

16.
J Microbiol Immunol Infect ; 50(5): 578-585, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26698687

RESUMO

BACKGROUND/PURPOSE: Along with the improving vaccine coverage, suspected vaccine-associated measles has been reported in Zhejiang Province, China. In order to maintain the accuracy of the measles surveillance system, it is critical to discriminate between measles vaccine and wild-type virus. METHODS: Eight suspected cases of vaccine-associated measles were reported in Zhejiang Province during 2011 and 2014. Sera collected within 4 days and throat swabs collected within 6 days after rash onset were tested with immunoglobulin M and measles virus (MeV) RNA to confirm MeV infection. In order to further identify the vaccine-associated cases, throat swabs with positive MeV RNA were tested using an allelic discrimination real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay developed in this study, RT-PCR-restriction fragment length polymorphism (RFLP) recommended by the National Measles Laboratory, and RT-PCR followed by sequencing and genotyping. RESULTS: Combining anti-measles immunoglobulin M and RNA testing, eight cases were confirmed as MeV infection. Of the eight, two were identified as vaccine-associated cases by the allelic discrimination rRT-PCR assay, and one was identified by RT-PCR-RFLP. Subsequent sequencing and genotyping confirmed that the sequences of the two cases were identical to that of the Chinese vaccine strain. The developed allelic discrimination rRT-PCR was 10 times more sensitive than the RT-PCR-RFLP assay when RNA standards generated from three genotypes of MeV were tested. CONCLUSION: Vaccine-associated measles has been identified in Zhejiang. The developed allelic discrimination rRT-PCR assay is rapid and sensitive, which will facilitate the surveillance for vaccine-associated measles.


Assuntos
Técnicas de Laboratório Clínico/métodos , Vacina contra Sarampo/efeitos adversos , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Sarampo/diagnóstico , Sarampo/virologia , Anticorpos Antivirais/sangue , Pré-Escolar , China/epidemiologia , Genótipo , Técnicas de Genotipagem , Humanos , Imunoglobulina M/sangue , Lactente , Sarampo/sangue , Sarampo/imunologia , Vacina contra Sarampo/genética , Vacina contra Sarampo/imunologia , Vírus do Sarampo/classificação , Vírus do Sarampo/isolamento & purificação , Polimorfismo de Fragmento de Restrição , RNA Viral/sangue , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade , Vacinação
17.
J Ethnopharmacol ; 189: 148-56, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27196295

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Decoction (HQD), a classical traditional Chinese medicine (TCM) formula, is used to treating liver injury in China. The aim of the study is to investigate mechanisms of HQD against dimethylnitrosamine (DMN)-induced liver fibrosis underlying metabolic profiles of bile acids. MATERIALS AND METHODS: DMN-induced liver fibrosis rats were administrated HQD and its compounds, astragalosides (AS), glycyrrhizic acid (GA) and their combination. The anti-fibrosis effects were evaluated and targeted metabolomics by UPLC-MS was used to examine whether HQD had an influence on bile acid metabolism. The levels of mRNAs associated with bile acid metabolism were expressed by RT-PCR. Chenodeoxycholic acid (CDCA)-induced hepatic stellate cells (HSCs) proliferation and activation were examined using MTS assay and Western blot. RESULTS: Histopathological changes and serum liver function in HQD group had significant improvements (P<0.01). Concentrations of free bile acids and taurine conjugates were significantly increased in DMN group (P<0.05). HQD and its compounds restored the increased bile acids to normal levels, and HQD was more effected on parts of bile acids. Furthermore, the levels of mRNAs related bile acid synthesis and reabsorption such as CYP7A1, CYP8B1, CYP27A1, OATP2, OATP3, OATP4 and NTCP were significantly down-regulated in DMN group (P<0.05), mRNAs related excretion such as MRP3 and BESP were up-regulated (P<0.01), and CYP7A1, CYP8B1, OATP3, OATP4, NTCP and MRP3 restored to normal levels by HQD treatment. Moreover, CDCA-induced HSCs proliferation and activation were weaken by HQD (P<0.05) with down-regulated α-SMA, TGF-ß1, p-Smad2 and p-Smad3 expressions. CONCLUSIONS: HQD alleviated DMN-induced liver fibrosis with a better effect than its compounds, which may be involved in the regulation of bile acid metabolism enzyme. Moreover, HQD may inhibit CDCA-induced HSCs proliferation and activation.


Assuntos
Ácidos e Sais Biliares/sangue , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dimetilnitrosamina , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Biomarcadores/sangue , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cromatografia Líquida de Alta Pressão , Regulação Enzimológica da Expressão Gênica , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/enzimologia , Células Estreladas do Fígado/patologia , Hidroxiprolina/metabolismo , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/patologia , Masculino , Espectrometria de Massas , Metabolômica/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar
18.
J Chromatogr A ; 1431: 36-46, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26777090

RESUMO

We report the template-free fabrication of three-dimensional hierarchical nanostructures, i.e., three-dimensional interconnected magnetic chemically modified graphene oxide (3D-Mag-CMGO), through a simple and low-cost self-assembly process using one-pot reaction based on solvothermal method. The excellent properties of the 3D-Mag-CMGO are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM), FTIR, elementary analyzer (EA) and X-ray photoelectron spectroscopy (XPS). The easiness-to-handle of the magnetic dispersive solid phase extraction (Mag-dSPE) procedure is developed for preconcentration of 21 allergenic disperse dyes from river water. The obtained results show the higher extraction capacity of 3D-Mag-CMGO with recoveries between 80.0-112.0%. Furthermore, an ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) method for determination of 21 allergenic disperse dyes in river at sub-ppt levels has been developed with pretreatment of the samples by Mag-dSPE. The limits of quantification (LOQs) for the allergenic disperse dyes are between 0.57-34.05ng/L. Validation results on linearity, specificity, trueness and precision, as well as on application to the analysis of 21 allergenic disperse dyes in fifty real samples demonstrate the applicability to environment monitoring analysis.


Assuntos
Alérgenos/análise , Cromatografia Líquida , Corantes/análise , Monitoramento Ambiental/métodos , Óxidos/química , Rios/química , Espectrometria de Massas em Tandem , Grafite/química , Magnetismo
19.
Int Immunopharmacol ; 30: 85-93, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26655878

RESUMO

Yinhuapinggan granule (YHPG), a Chinese medicine granule on the basis of Ma-Huang-Tang (Ephedra Decoction) and the clinical experience of Professor Wan Haitong, has been shown to inhibit the growth of influenza virus in vitro. The aim of this study was to investigate the protective effects of YHPG on mice with influenza viral pneumonia and its effects on regulating related inflammatory cytokines in influenza virus A-infected mice. ICR mice were inoculated intranasally with 15 LD50 viral dose of influenza virus A/PR/8/34 (H1N1) and treatments with YHPG (7.5, 15 and 30g/kg) were orally administrated daily for 5 consecutive days after challenge, respectively. The results showed that mortality rate, lung index, lung histopathological changes, IL-6 and TNF-α in serum were significantly attenuated in the treatment of YHPG (15 and 30g/kg) than those in the IFV control group, while the levels of IL-2 was significantly enhanced. Moreover, the RT-PCR results revealed that YHPG (15 and 30g/kg) significantly depressed the expressions of IL-1ß, IFN-γ and TNF-α mRNA in lung tissues. Furthermore, the immunohistochemical staining results also revealed that the expression of NF-κB p65 proteins was downregulated when treated with YHPG (15 and 30g/kg). These results showed YHPG has protective effects on IFV-infected mice, due to its ability of alleviation of lung damage, regulation of the cytokine production via inhibiting the NF-κB p65 activation, attenuation of systemic and pulmonary inflammatory responses.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Vírus da Influenza A/imunologia , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Animais , Citocinas/genética , Citocinas/metabolismo , Pulmão/imunologia , Pulmão/virologia , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , Infecções por Orthomyxoviridae/complicações , Pneumonia Viral/etiologia
20.
Chin Med ; 10: 39, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26691002

RESUMO

BACKGROUND: Huangqi decoction (HQD) is used for liver fibrosis and cirrhosis treatment in Chinese medicine. This study aims to investigate the pharmacological actions of HQD against liver fibrosis in rats by high-throughput gene expression profiling, network analysis and real-time qRT-PCR. METHODS: We analyzed the profiles of differentially expressed genes (DEGs) in dimethylnitrosamine (DMN)-induced liver fibrosis in rat. The liver tissue samples of control group (n = 3), model group (n = 3) and HQD group (n = 3) were examined by microarrays. Pathways were analyzed by KEGG. Pathway-gene and protein-protein interaction (PPI) networks were constructed with Cytoscape software. The expression of candidate genes was verified by qRT-PCR. P values less than 0.05 indicated statistical significance. RESULTS: Collagen deposition and hydroxyproline (Hyp) content were decreased in the HQD group compared with the model group (P < 0.001), while that of Hyp in the model group were increased compared with the control group (P < 0.001). In comparison with the model group, 1085 DEGs (all P < 0.05, |fold change| >1.5) and 52 pathways in the HQD group were identified. TGF-beta, ECM-receptor interaction, and the cell adhesion molecules pathways were significantly recovered by HQD (P < 0.001). A pathway-gene network was constructed, including 303 DEGs and 52 pathways, and 514 nodes and 2602 edges, among 142 genes with node degrees greater than 10. The expressions of PDGFra, PDGFrb, PDGFb, PDGFd, COL1A1, COL1A2, COL5A2, and THBS1 were significantly down-regulated by HQD (P < 0.001). CONCLUSION: HQD down-regulated the expressions of PDGFra, PDGFrb, PDGFb, PDGFd, COL1A1, COL1A2, COL5A2 and THBS1, and TGF-ß and PDGF signaling pathways in the DMN-induced liver fibrosis in rats.

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