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1.
Front Microbiol ; 11: 594820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193273

RESUMO

Human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T cells in the gut plays an insidious role in acquired immunodeficiency syndrome (AIDS) pathogenesis. Host immune function is closely related to gut microbiota. Changes in the gut microbiota cause a different immune response. Previous studies revealed that HIV-1 infection caused changes in gut microbiota, which induced immune deficiency. HIV-1 infection results in an abnormal composition and function of the gut microbiota, which may disrupt the intestinal epithelial barrier and microbial translocation, leading to long-term immune activation, including inflammation and metabolic disorders. At the same time, an abnormal gut microbiota also hinders the effect of antiviral therapy and affects the immune reconstruction of patients. However, studies on the impact of the gut microbiota on immune reconstitution in patients with HIV/AIDS are still limited. In this review, we focus on changes in the gut microbiota caused by HIV infection, as well as the impact and regulation of the gut microbiota on immune function and immune reconstitution, while we also discuss the potential impact of probiotics/prebiotics and fecal microbiota transplantation (FMT) on immune reconstitution.

2.
Eur J Pharmacol ; 889: 173493, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32860808

RESUMO

Gastric cancer (GC) is one of the most common malignant neoplasms of the digestive system, with China leading in terms of morbidity and mortality rates. Betulinic acid (BA) is a widely-occurring pentacyclic triterpenoid that has been reported to exhibit potent anti-inflammatory, antioxidant, and antitumor activities. BA can combat tumors by inducing apoptosis, regulating cell cycle, and inhibiting autophagy, but its mechanism of action in the context of GC is unclear. A preliminary study found that higher expression of vasodilator-stimulated phosphoprotein (VASP) was correlated with migration in the GC cell line. In this study, BGC-823 cells and MNK45 cells were treated with BA for investigating its effect on the proliferation and migration of cells. Moreover, the expression of VASP and upstream signal molecules were also investigated in this background. The results showed BA could inhibit the proliferation and migration the GC cells. Furthermore, NF-κB acted as a transcription factor to upregulate VASP expression. Moreover, BA could downregulate the expression of VASP at the protein and mRNA level by inhibiting NF-κB activity. In conclusion, these results suggest that BA could inhibit the expression of VASP by negatively regulating NF-κB, thereby inhibiting the proliferation and migration of the GC cells. Our study provides a theoretical basis for exploring the molecular mechanism underlying BA-induced inhibition of proliferation and migration in GC cells.

3.
Int J Clin Pharmacol Ther ; 58(7): 375-386, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32301702

RESUMO

OBJECTIVE: This study evaluated different influences of 14 single nucleotide polymorphisms (SNPs) and demographic factors leading to individual differences in the antihypertensive efficacy of felodipine in healthy Chinese subjects. MATERIALS AND METHODS: 24 subjects were sequenced for candidate SNPs. Plasma samples were obtained as clinical trial protocol, and were determined by a HPLC-MS/MS method. Pharmacokinetic parameters were calculated by WinNonlin 6.0. Statistical analysis was mainly performed by SPSS 22.0. A multiple linear regression model provided different weight coefficients of different demographic and genetic factors. RESULTS: The trend of Cmax is almost consistent with AUCss increase, but tmax of individuals is different; the antihypertensive effect of felodipine is individually different. A significant association was observed between systolic blood pressure decrease (ΔSBP) and SNPs of CACNA1C, CACNA1D, GNB3 respectively, while CACNA1C and CACNA1 were associated with diastolic blood pressure decrease (ΔDBP). CYP3A5 rs766746 and CYP3A4 rs2242480 were linked with Cmax and AUCss, and ABCB1 rs1045642 was associated with T1/2. Significant relationships were shown between AUCss and ΔSBP (p = 0.022) as well as Cmax and ΔSBP (p = 0.015). CONCLUSION: The efficacy of felodipine is individually different, influenced especially by CACNA1C rs1051375 and ABCB1 rs1045642. ΔDBP is associated with ΔSBP in multiple-dosing of felodipine in healthy Chinese subjects.


Assuntos
Anti-Hipertensivos , Felodipino , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Anti-Hipertensivos/farmacologia , Grupo com Ancestrais do Continente Asiático/genética , Canais de Cálcio Tipo L/genética , Citocromo P-450 CYP3A , Felodipino/farmacologia , Humanos , Espectrometria de Massas em Tandem
4.
World J Clin Cases ; 8(1): 11-19, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31970165

RESUMO

BACKGROUND: As one of the subsets of CD8+ T cells, Tc17 cells have recently been identified and are characterized by the secretion of interleukin (IL)-17, which is related to inflammatory diseases. AIM: To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development. METHODS: Flow cytometry assay, immunohistochemistry, and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer. Prior to cell suspension culture, ELISA was carried out to measure the production of IL-6, IL-1ß, IL-23, CXCL12, and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer. In addition, multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model. RESULTS: Compared with normal tissues, Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients. Cancer cells produced a greater amount of IL-6, IL-1ß, and IL-23, which in turn promoted Tc17 cell polarization. Unlike the traditional cytotoxic CD8+ T cells, Tc17 cells secreted IL-17, which subsequently promoted CXCL12 expression in tumor cells, eventually enhancing the proliferation and migration of tumor cells. Thus, the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer. CONCLUSION: Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer. We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.

5.
Medicine (Baltimore) ; 98(50): e18362, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852141

RESUMO

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS: We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS: Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION: For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas , Veia Porta/cirurgia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Tratamento Conservador/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa
6.
J Biochem Mol Toxicol ; 33(11): e22394, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31557376

RESUMO

Triptolide (TP), a major active ingredient of Tripterygium wilfordii, exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC-MS/MS approach was employed to explore the endocrine-disrupting effects of TP. The endocrine-disrupting effects of various concentrations (0-100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability. The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real-time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 µg/kg) for 28 days on both normal and collagen-induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 µg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2, CYP21A2, CYP17A1, and CYP11B1, which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.


Assuntos
Corticosteroides/metabolismo , Diterpenos/toxicidade , Hormônios Gonadais/metabolismo , Fenantrenos/toxicidade , Extratos Vegetais/toxicidade , Córtex Suprarrenal/patologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Compostos de Epóxi/toxicidade , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Progesterona Redutase/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Esteroide Hidroxilases/metabolismo , Espectrometria de Massas em Tandem , Tripterygium/química
7.
J Sep Sci ; 42(22): 3395-3402, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31508887

RESUMO

The ripened seeds of Strychnos nux-vomica L. have been extensively used as herbal medicines in Asian countries. Dihydroindole-type alkaloids are not only the active constituents but also the toxicants in Strychnos. However, the simultaneous determination of these alkaloids in both crude and processed Semen Strychni is still lacking. The present study represents the first quantitation and relative quantitation assay of 12 dihydroindole-type alkaloids in Strychnos nux-vomica unprocessed and sand-processed seeds using high-performance liquid chromatography coupled with diode array detection and mass spectrometry. The relative concentration of ten alkaloids was calculated by semi-quantification using the internal standard and their amounts in unprocessed and detoxified Semen Strychni were compared. We report here for the first time the significant increase of the two alkaloids, 19-N-methyl-strychnine, and 2,3-dimethoxy-19-N-methyl-strychnine, during the processing of Semen Strychni. Our study provides new insight into the true complexity of seed processing procedure and valuable information for assessing the efficacy and safety for clinical applications of Semen Strychni-containing drugs.


Assuntos
Alcaloides Indólicos/análise , Sementes/química , Strychnos nux-vomica/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Estrutura Molecular
8.
Surg Oncol ; 29: 159-167, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31196483

RESUMO

BACKGROUND AND AIMS: Serum ferritin (SF) may have a close relationship with the tumor. But no study has investigated the prognostic value of SF in hepatocellular carcinoma (HCC) patients receiving curative resection yet. Aim of this study is to explore the role of preoperative SF in survival outcomes of such patients. METHODS: We retrospectively analyzed 427 HCC patients who received curative hepatic resection in our medical center. Significant clinical and pathological data along with the association between SF and clinicopathological parameters were compared and analyzed. The prognostic significance of SF was determined by Kaplan-Meier analysis and the Cox proportional hazards regression model. RESULTS: The optimal cut-off value of SF for overall survival (OS) was 267 ng/ml. Preoperative SF level could predict OS (P = 0.001, HR = 1.651, 95%CI: 1.213-2.247) and recurrence-free survival (RFS) (P < 0.001, HR = 1.570, 95%CI: 1.221-2.018) independent of other prognostic factors. Patients with a low SF were more likely to have both favorable OS and RFS (both P < 0.001), and vice versa. The 1-, 3-, and 5-year OS and RFS rates were 91.4%, 80.1%, 71.7%, and 78.0%, 53.0%, 47.3% in low SF group, and 91.6%, 60.2%, 45.2%, and 61.3%, 36.4%, 29.0% in high SF group, respectively. CONCLUSIONS: Preoperative SF was a simple, inexpensive, convenient and reliable prognostic factor that could predict survival outcomes in HCC patients who received radical hepatic resection.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Ferritinas/sangue , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Cuidados Pré-Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
9.
Cancer Med ; 8(4): 1679-1693, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30806044

RESUMO

Breast cancer is one of the most common malignant tumors among women worldwide. About 70-75% of primary breast cancers belong to estrogen receptor (ER)-positive breast cancer. In the development of ER-positive breast cancer, abnormal activation of the ERα pathway plays an important role and is also a key point leading to the failure of clinical endocrine therapy. In this study, we found that the small molecule peptide chlorotoxin (CTX) can significantly inhibit the proliferation, migration and invasion of breast cancer cells. In in vitro study, CTX inhibits the expression of ERα in breast cancer cells. Further studies showed that CTX can directly bind to ERα and change the protein secondary structure of its LBD domain, thereby inhibiting the ERα signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ERα signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ERα/VASP signaling pathway. In in vivo study, CTX significantly inhibits growth of ER overexpressing breast tumor and, more importantly, based on the mechanism of CTX interacting with ERα, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti-ER-positive breast cancer, which also provides an important reference for the study of CTX anti-ER-related tumors.


Assuntos
Moléculas de Adesão Celular/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Venenos de Escorpião/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Moléculas de Adesão Celular/química , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Charibdotoxina/química , Charibdotoxina/isolamento & purificação , Charibdotoxina/farmacologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/genética , Fosfoproteínas/química , Fosfoproteínas/genética , Ligação Proteica , Venenos de Escorpião/química , Venenos de Escorpião/isolamento & purificação
10.
Asian J Surg ; 42(12): 981-989, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30782497

RESUMO

BACKGROUND: Portal hypertension (PH), which is closely associated with the severity of liver cirrhosis, has been suggested as a contraindication of liver resection for hepatocellular carcinoma (HCC). We aimed to explore the role of a potential player, histologic severity of liver cirrhosis, in affecting surgical outcomes of the patients with both HCC and PH. METHODS: A total of 374 HCC patients with PH underwent resection for HCC were retrospectively reviewed. By using the Laennec staging system, the patients were divided into two groups: the mild-moderate cirrhosis (MMC) group and the severe cirrhosis (SC) group. Propensity score matching (PSM) was conducted at a 1:1 ratio between the two groups, and 89 patients were matched for each group. Short-term and long-term outcomes were compared between two groups before and after PSM. RESULTS: The overall morbidity and 30-days mortality were significantly higher in the SC group than the MCC group (52.9% vs. 30.1%, P < 0.001 and 6.9% vs. 0.7%, P = 0.002). Severe cirrhosis was identified as an independent predictor of postoperative liver-related complications. Patients with MMC exhibited better 5-year overall survival (39.9% vs. 16.9%, P < 0.001) and disease-free survival (10.5% vs. 4.4%, P < 0.001) than those with SC. Multivariate analysis indicated that severe cirrhosis was significantly associated with lower disease-free survival and overall survival. These results were further confirmed in the PSM cohort. CONCLUSIONS: Histologic severity of liver cirrhosis determines the surgical outcomes of patients with both HCC and PH, and PH is not an absolute contraindication of liver resection.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hipertensão Portal/complicações , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
11.
Cell Death Dis ; 10(2): 60, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683838

RESUMO

The authors have retracted the article [Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma, Cell Death & Disease volume 7, page e2388 (2016), doi 10.1038/cddis.2016.260] because it has recently come to their attention that the A549 cells used in this research were contaminated with Hela cells, which may have altered the outcome of their experiment. The conclusions of this article are therefore unreliable. All authors agree to this retraction.

12.
Gene ; 678: 349-360, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30098429

RESUMO

OBJECTIVES: To conduct an integrated analysis of microRNA and mRNA expression profile and further discover vital molecules to uncover novel pathogenic mechanisms in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: MicroRNA and mRNA expression profiles were obtained from six paired primary SACC tumors and corresponding adjacent normal glands using high-throughput next-generation sequencing technology followed by an overall integrated bioinformatics analysis and subsequently molecular biology techniques validation. RESULTS: Compared with adjacent noncancerous normal gland, 2107 significant differentially expressed mRNA were determined in SACC. Gene ontology and KEGG pathway analysis suggested that the differentially expressed genes were relevant to many significant biological implications. Venn diagram analysis of differentially expressed genes in different group identified 29 differentially expressed overlapping mRNA. 40 differentially expressed microRNAs were also identified in SACC. Furthermore, integrated analysis of microRNA and mRNA expression profiles recognized a core microRNA-mRNA regulatory network and unmasked many novel genes including SCUBE3, CA6, hsa-miR-885-5p and other molecules which may play an essential role in the carcinogenesis of SACC. Also, Q-PCR and immunohistochemistry results reveal the high expression and distribution of SCUBE3 in SACC and dual luciferase reporter assay also preliminarily validated that SCUBE3 was a target of hsa-miR-885-5p. CONCLUSION: Contemporary microRNA/mRNA analysis have uncovered many mRNAs and microRNAs worthy further exploration in SACC. These are bound to help us shed light on the overall genetic background of SACC and further elucidate the potential molecular mechanism of SACC.


Assuntos
Carcinoma Adenoide Cístico/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , RNA Mensageiro/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Proteínas de Ligação ao Cálcio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos , Adulto Jovem
13.
Cell Death Dis ; 9(8): 829, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082717

RESUMO

Following publication of their article, the authors noticed that there were minor errors in Figs. 3, 7 and S5. The errors had no effect on the scientific content or conclusions. The rectified figures are given below.

14.
Cancer Med ; 7(8): 3875-3888, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29968965

RESUMO

Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF-7 cells and increase the proportion of MCF-7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA-MB-231 cells and increased the proportion of MDA-MB-231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG-132 showed that IQUB activated Akt to promote GSK3ß phosphorylation, which in turn activated Wnt/ß-catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3ß/ß-catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , beta Catenina/metabolismo , Adulto , Idoso , Apoptose/genética , Neoplasias da Mama/diagnóstico , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Modelos Biológicos , Gradação de Tumores , Estadiamento de Neoplasias , Via de Sinalização Wnt
15.
Front Pharmacol ; 9: 732, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034340

RESUMO

Saikosaponin d (SSd) is a major hepatoprotective component of saikosaponins derived from Radix Bupleuri, which was also linked to hepatotoxicity. Previous studies have demonstrated that caspases play a key role in SSd-induced liver cell death. Our in vitro and in vivo studies also showed that treatment with caspase inhibitor z-VAD-fmk could significantly reduce the L02 hepatocyte cells death and lessen the degree of liver damage in mice caused by SSd. In order to further reveal the underlying mechanisms of caspase inhibition in SSd-induced hepatotoxicity, mass spectrometry based untargeted metabolomics was conducted. Significant alterations in metabolic profiling were observed in SSd-treated group, which could be restored by caspase inhibition. Bile acids and phospholipids were screened out to be most significant by spearman correlation analysis, heatmap analysis and S-Plot analysis. These findings were further confirmed by absolute quantitation of bile acids via targeted metabolomics approach. Furthermore, cytokine profiles were analyzed to identify potential associations between inflammation and metabolites. The study could provide deeper insight into the hepatotoxicity of SSd and the efficacy of caspase inhibition.

16.
Medicine (Baltimore) ; 97(25): e11174, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924030

RESUMO

RATIONALE: Portal vein thrombosis is defined as any thrombosis that develops in the portal vein system. It is considered a very rare and extremely lethal complication of hepatopancreatobiliary surgery. PATIENT CONCERNS: Acute portal vein thrombosis after hepatectomy in patients with hepatolithiasisis very rare. Acute portal vein thrombosis is considered as a dangerous complication after hepatectomy. It is easy to ignore the symptom of acute portal vein thrombosis. Once the appropriate time of treatment is past, it would lead to patients' death. DIAGNOSE: Acute portal vein thrombosis after hepatectomy in a patient with hepatolithiasis INTERVENTIONS:: We consider anticoagulation therapy and percutaneous transhepatic portal vein puncture and thrombectomy once the diagnosis of acute portal vein thrombosis is confirmed. OUTCOMES: The patient's liver function continued to deteriorate, eventually resulting in death. LESSONS: Acute portal vein thrombosis after hepatectomy is difficult to diagnose. The management of acute portal vein thrombosis remains controversial according to its severity, location or time of discovering.


Assuntos
Sistema Biliar/patologia , Hepatectomia/efeitos adversos , Veia Porta/patologia , Trombose Venosa/complicações , Doença Aguda , Administração Intravenosa , Adulto , Anticoagulantes/uso terapêutico , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Evolução Fatal , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Hepatopatias/cirurgia , Masculino , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Complicações Pós-Operatórias/cirurgia , Trombectomia/métodos , Ultrassonografia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/cirurgia
17.
Arch Oral Biol ; 93: 141-148, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29913322

RESUMO

OBJECTIVES: The aim of the present study was to investigate whether tumor-derived supernatants down-regulate the immune function of plasmacytoid dendritic cells (pDCs) in oral cancer and the potential molecular mechanisms of this effect. MATERIALS AND METHODS: Immunohistochemistry (IHC) and flow cytometry were used to detect tumor-infiltrating and peripheral blood pDCs. MTS and flow cytometry were employed to evaluate the immune response of CD4+ T cells. Real-time PCR and ELISA assays were used to identify TLR-7 and TLR-9 expression, IFN-α production and tumor-secreted soluble cytokines. RESULTS: The proportion of pDCs (0.121%±0.043%) was significantly higher in Oral squamous cell carcinoma (OSCC) samples than in normal tissue (0.023%±0.016%) (P = 0.021). TLR9 mRNA was significantly lower in tumor-infiltrating pDCs and positively correlated to low IFN-α production (r = 0.956; P<0.01). The supernatant of oral cancer cells negatively regulated TLR9 mRNA expression and the subsequent IFN-α production of pDCs, which inhibited the immune response of CD4+ T cells. The neutralizing antibodies blocking assay showed that the specific inhibitory effect of pDC functionality was associated with the soluble fraction of the oral cancer environment, which is mainly mediated by IL-10 and TGF-ß cooperation. CONCLUSION: Tumor-derived supernatants may impair the function of tumor-infiltrating pDCs, which subsequently decreases the immune response of CD4+ T cells in human oral cancer through TGF-ß- and IL-10- dependent mechanisms. Careful manipulation of these impaired pDCs may help develop an important alternative immunotherapy for the treatment of oral cancer.


Assuntos
Carcinoma de Células Escamosas/imunologia , Células Dendríticas/imunologia , Interferon-alfa/metabolismo , Neoplasias Bucais/imunologia , Receptor Toll-Like 9/metabolismo , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Células Tumorais Cultivadas
18.
J Virol Methods ; 257: 85-92, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29703616

RESUMO

Plasmid bearing adenovirus genome is generally constructed with the method of homologous recombination in E. coli BJ5183 strain. Here, we utilized Gibson gene assembly technique to generate infectious clone of fowl adenovirus 4 (FAdV-4). Primers flanked with partial inverted terminal repeat (ITR) sequence of FAdV-4 were synthesized to amplify a plasmid backbone containing kanamycin-resistant gene and pBR322 origin (KAN-ORI). DNA assembly was carried out by combining the KAN-ORI fragment, virus genomic DNA and DNA assembly master mix. E. coli competent cells were transformed with the assembled product, and plasmids (pKFAV4) were extracted and confirmed to contain viral genome by restriction analysis and sequencing. Virus was successfully rescued from linear pKFAV4-transfected chicken LMH cells. This approach was further verified in cloning of human adenovirus 5 genome. Our results indicated that DNA assembly technique simplified the construction of infectious clone of adenovirus, suggesting its possible application in virus traditional or reverse genetics.


Assuntos
Aviadenovirus/crescimento & desenvolvimento , Aviadenovirus/genética , DNA Viral/genética , Genética Reversa/métodos , Animais , Linhagem Celular , Galinhas , Escherichia coli/genética , Plasmídeos , Recombinação Genética , Transfecção
19.
Front Pharmacol ; 9: 236, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29615909

RESUMO

The quality control research of traditional Chinese medicine (TCM) is lagged far behind the space of progress in modernization and globalization. Thus the concept of quality marker (Q-marker) was proposed recently to guide the quality investigations of TCM. However, how to discover and validate the Q-marker is still a challenge. In this paper, a system pharmacology based strategy was proposed to discover Q-marker of HuangQin decoction (HQD) to attenuate Intestinal Damage. Using this strategy, nine measurable compounds including paeoniflorin, baicalin, scutellarein, liquiritigenin, norwogonin, baicalein, glycyrrhizic acid, wogonin, and oroxylin A were screened out as potential markers. Standard references of these nine compounds were pooled together as components combination according to their corresponding concentration in HQD. The bioactive equivalence between components combination and HQD was validated using wound healing test and inflammatory factor determination experiment. The comprehensive results indicated that components combination is almost bioactive equivalent to HQD and could serve as the Q-markers. In conclusion, our study put forward a promising strategy for Q-markers discovery.

20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(6): 828-833, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29260515

RESUMO

OBJECTIVE: To explore the changes of micro RNA 155 (miR-155),BTB and CNC homologous protein 1 (BACH1),quinone oxidoreductase 1 (NQO1) and heme-oxygenase-1 (HO-1) in the process of arsenic trioxide-induced cell death,and to clarify the relationship between miR-155 and BACH1,providing experimental basis for the sensitivity of arsenic trioxide (ATO) treatment. METHODS: Human lung adenocarcinoma cell line A549 cells were treated with different concentrations of ATO. MTT assay and total antioxidant capacity detection kit were used to determine cell viability and total antioxidant capacity,respectively. BACH1,NQO1 and HO-1 protein expression were probed by Western blot and real-time fluorescence quantitative (qRT-PCR) was utilized to test the miR-155 level. A549 cells were transfected with miR-155 mimic and its negative control,then the expression level of miR-155 was detected by qRT-PCR,and these cells were treated with 20 µmol/L for 24 h followed by MTT and Western blot detection. RESULTS: 10 µmol/L ATO significantly reduced the cell viability in A549 cells. 10 µmol/L and 20 µmol/L ATO treatment activated BACH1 expression and inhibited miR-155,NQO1 and HO-1 expression,leading to decreased total antioxidant capacity. Importantly,the cell death induced by 20 µmol/L ATO was significantly decreased in miR-155 mimic transfection cells in comparison with non-transfected cells and miR-155 mimic negative control transfected cells. Moreover,high expression of miR-155 reduced BACH1 activation and increased NQO1 and HO-1 expression in cells treated with 20 µmol/L ATO ( P<0.05). CONCLUSION: Restraining total antioxidant capacity contributes to ATO induced cell death,the underlying mechanisms may be that ATO can activate BACH1 expression through inhibition of the miR-155 level,leading to subsequent inhibition of NQO1 and HO-1 expression. Taken together,these data suggest that miR-155 and BACH1 could be used as sensitivity targets for ATO treatment in lung cancer.


Assuntos
Adenocarcinoma/genética , Arsenicais/farmacologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Óxidos/farmacologia , Transdução de Sinais , Adenocarcinoma de Pulmão , Apoptose , Trióxido de Arsênio , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Heme Oxigenase-1/genética , Humanos , NAD(P)H Desidrogenase (Quinona)/genética
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