Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
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.

2.
Transl Androl Urol ; 9(3): 1244-1251, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32676407

RESUMO

Background: The treatment of ketamine-induced bladder contractures remains poorly studied. We therefore evaluated the efficacy of cystectasia with a sodium hyaluronate balanced solution in this kind of bladder contracture. Methods: Eighteen patients presenting with ketamine-induced bladder contracture between July 2010 and February 2018 were selected and analysed. Ketamine was discontinued in all patients, who were then treated with weekly cystectasia (0.09% sodium hyaluronate balanced solution) 3 times. The volume of the first perfusion was twice the preoperatively measured bladder capacity, and the volume of the subsequent two perfusions was increased by 100 mL each time. The Pelvic Pain and Urgency/Frequency (PUF) symptom score, O'Leary-Sant Interstitial Cystitis (IC) Symptom Index (ICSI), IC Problem Index (ICPI), Quality of Life (QOL) score, and bladder capacity were recorded before surgery and 3 and 12 months after the 3rd expansion. Results: No significant complications were observed during the 3 expansions. Fourteen patients completed the full follow-up schedule. Preoperatively and at the 3- and 12-month follow-up evaluations performed after the 3rd expansion, the PUF symptom scores were 20.4±3.6, 11.5±3.1, and 13.2±3.3, respectively; the mean ICSI was 13.6±2.8, 7.7±2.3, and 8.2±2.5, respectively; the mean ICPI was 10.6±2.6, 7.3±2.1, and 7.7±2.5, respectively; and the mean QOL scores were 6.0±0, 2.1±0.5, and 2.7±0.8, respectively; and the mean bladder catheter volume was 83±27, 234±56, and 228±52 mL, respectively. There were significant differences between all preoperative and postoperative values. Conclusions: Cystectasia with a sodium hyaluronate balanced solution is an effective treatment modality for ketamine-induced bladder contracture.

3.
Int J Infect Dis ; 97: 278-282, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32502664

RESUMO

OBJECTIVES: Although COVID-19 is known to be caused by human-to-human transmission, it remains largely unclear whether ambient air pollutants and meteorological parameters could promote its transmission. METHODS: A retrospective study was conducted to study whether air quality index (AQI), four ambient air pollutants (PM2.5, PM10, NO2 and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase COVID-19 incidence in Wuhan and XiaoGan between Jan 26th to Feb 29th in 2020. RESULTS: First, a significant correlation was found between COVID-19 incidence and AQI in both Wuhan (R2=0.13, p<0.05) and XiaoGan (R2=0.223, p<0.01). Specifically, among four pollutants, COVID-19 incidence was prominently correlated with PM2.5 and NO2 in both cities. In Wuhan, the tightest correlation was observed between NO2 and COVID-19 incidence (R2=0.329, p<0.01). In XiaoGan, in addition to the PM2.5 (R2=0.117, p<0.01) and NO2 (R2=0.015, p<0.05), a notable correlation was also observed between the PM10 and COVID-19 incidence (R2=0.105, p<0.05). Moreover, temperature is the only meteorological parameter that constantly correlated well with COVID-19 incidence in both Wuhan and XiaoGan, but in an inverse correlation (p<0.05). CONCLUSIONS: AQI, PM2.5, NO2, and temperature are four variables that could promote the sustained transmission of COVID-19.


Assuntos
Poluição do Ar/efeitos adversos , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Temperatura , Betacoronavirus , Monóxido de Carbono/efeitos adversos , China/epidemiologia , Cidades , Infecções por Coronavirus/transmissão , Humanos , Incidência , Dióxido de Nitrogênio/efeitos adversos , Pandemias , Material Particulado/efeitos adversos , Pneumonia Viral/transmissão , Estudos Retrospectivos
4.
Chin J Integr Med ; 26(12): 936-942, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32572781

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of Tanreqing Injection (, TRQI) combined with conventional treatment on clinical outcomes in the treatment of patients with influenza. METHODS: The electronic databases searched were Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (PubMed), EMbase (OvidSP), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP) and WanFang Data Knowledge Service Platform, and we checked the reference sections of the retrieved articles as well. The search was performed in October 2018, and we used the randomized controlled trials (RCTs) that corresponded to the new diagnostic criteria for influenza. Two review authors independently screened the internalized articles in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement checklist. We evaluated the quality of the articles and extracted the data from the studies using the Revmen5.3 software. RESULTS: We included 12 RCTs of over 882 cases in this meta-analysis. Compared to conventional treatment, TRQI combined with conventional treatment could increase the total effective rate [9 RCTs, n=648, odds ratio (OR): 4.92, 95% confidence interval (CI): 2.94, 8.24, P<0.0001, random effects model], decrease the average time for fever clearance [7 RCTs, n=564, mean difference (MD): -1.08, 95% CI: -1.68, -0.48, P=0.0004, random effects model] and decrease the time for resolution of cough (5 RCTs, n=362, MD: -1.76, 95% CI: -2.63, -0.90, P<0.0001, random effects model). CONCLUSION: Based on this meta-analysis of RCTs, TRQI combined with conventional treatment had a statistically significant benefit in increasing the total effective treatment rate and reducing the time for fever clearance as well as time for resolution of cough.

5.
Breast Cancer ; 27(3): 363-371, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31728872

RESUMO

BACKGROUND: Breast cancer has become a dangerous killer for the female, which seriously threatened women's life, leading to huge pressures to society. The present study assessed the mechanism underlying the involvement of bone marrow tyrosine kinase on chromosome X (BMX) in breast cancer development. METHODS: The expression of BMX was examined by qPCR and immunohistochemistry. The effect of BMX on cell proliferation and migration was detected by Clone formation assay and Transwell assay. In vitro study, the correlation of BMX with Wnt/ß-catenin pathway was explored by western blot and TOP/FOP flash assay. RESULTS: In the present study, we found that BMX was up-regulated in breast cancer, which was associated with the tumor differentiation and TNM stage. Oncogenic BMX enhanced the ability of breast cancer cell proliferation and migration. Furthermore, BMX could up-regulate the protein expression levels of p-ß-catenin (Y142), p-ß-catenin(Y654) and inhibit the expression level of p-ß-catenin (S33/37), thus activating Wnt/ß-catenin pathway in MCF-7 and MDA-MB-231 cells. In addition, we revealed that BMX promoted GSK3ß phosphorylation, which suppressed the degradation of ß-catenin. CONCLUSIONS: In this study, we identified that BMX-activated Wnt/ß-catenin signaling pathway, playing an oncogenic role in breast cancer, suggesting that BMX could become a potential treatment target of breast cancer.

6.
Int J Biol Sci ; 15(12): 2733-2749, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754343

RESUMO

Breast cancer is one of the most common malignant tumors worldwide. Metastasis remains the leading cause of death in breast cancer patients. Research on the mechanism of breast cancer metastasis has become a core issue in breast cancer research. Our previous series of studies have shown that VASP, as a key oncogene, plays an important role in the development of various tumors such as breast cancer. In this study, we find that miR-638 can target to inhibit VASP expression, and Lin28 acts as an RNA-binding protein to regulate the processing of miR-638, which inhibits its maturation and promotes the expression of VASP. In addition, we also find that CREB1 acts as a transcription factor that binds to the promoter of Lin28 gene and activates the Lin28/miR-638/VASP pathway. Furthermore, CREB1 can also directly bind to the promoter of VASP, and activate VASP expression, forming a CREB/Lin28/miR-638/VASP interactive network, which plays an important role in promoting cell proliferation and migration in breast cancer. Our study explained the mechanism of CREB1/Lin28/miR-638/VASP network promoting the development of breast cancer, which further elucidated the mechanism of VASP as a key oncogene, and also provided a theoretical basis for expanding new approaches to tumor biotherapy.


Assuntos
Neoplasias da Mama/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Biomarcadores Tumorais , Neoplasias da Mama/genética , Moléculas de Adesão Celular/genética , Proliferação de Células , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Fator de Crescimento Epidérmico/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Proteínas dos Microfilamentos/genética , Neoplasias Experimentais , Fosfoproteínas/genética , Prognóstico , Mapas de Interação de Proteínas , Proteínas de Ligação a RNA/genética , Cicatrização
7.
Pathol Res Pract ; 215(10): 152575, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31387807

RESUMO

The important role of LncRNA in the development of breast cancer is attracting more and more attention. In the previous study, we found that the expression level of LncRNA SNHG6 in breast cancer tissues and cells was significantly increased, but its mechanism in the development of breast cancer was still unclear. Our study found that knockdown of SNHG6 significantly inhibited the proliferation, migration and invasion of breast cancer cells MCF-7 and MDA-MB-231 cells. Further study showed that knockdown of SNHG6 significantly inhibited the expression level of VASP. More importantly, SNHG6 and VASP both can bind directly to miR-26a, suggesting that SNHG6 could act as a ceRNA to sponge miR-26a, thereby promoting the expression of VASP, which leading to activated proliferation, migration and invasion of breast cancer cells. Taken together, this study revealed the important role of the SNHG6/miR-26a/VASP regulatory network in the development of breast cancer, and provided a reference for exploring new pathogenesis and biomarkers of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Moléculas de Adesão Celular/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Invasividade Neoplásica/genética , Fosfoproteínas/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Inativação Gênica , Humanos , Invasividade Neoplásica/patologia , RNA Longo não Codificante/genética
8.
Oxid Med Cell Longev ; 2019: 8194804, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341536

RESUMO

Generally, inflammatory bowel disease (IBD) can be caused by psychology, genes, environment, and gut microbiota. Therefore, IBD therapy should be improved to utilize multiple strategies. Shen Ling Bai Zhu San (SLBZS) adheres to the aim of combating complex diseases from an integrative and holistic perspective, which is effective for IBD therapy. Herein, a systems pharmacology and microbiota approach was developed for these molecular mechanisms exemplified by SLBZS. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, potential active compounds and their corresponding direct targets were retrieved. Then, the network relationships among the active compounds, targets, and disease were built to deduce the pharmacological actions of the drug. Finally, an "IBD pathway" consisting of several regulatory modules was proposed to dissect the therapeutic effects of SLBZS. In addition, the effects of SLBZS on gut microbiota were evaluated through analysis of the V3-V4 region and multivariate statistical methods. SLBZS significantly shifted the gut microbiota structure in a rat model. Taken together, we found that SLBZS has multidimensionality in the regulation of IBD-related physiological processes, which provides new sights into herbal medicine for the treatment of IBD.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Humanos , Microbiota
9.
Mol Med Rep ; 20(2): 1943-1951, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257464

RESUMO

Saikosaponin b2 (SSb2) can be extracted from Bupleurum spp. roots (Radix Bupleuri), which belongs to the Umbelliferae family. The current study aimed to explore the effects of SSb2 on proliferation of breast cancer cells and to identify the mechanism by which SSb2 affects breast cancer cell migration. mRNA expression levels of STAT3 and vasodilator­stimulated phosphoprotein (VASP) were determined and increased expression was observed in 16 breast cancer tissues compared with the paracancerous tissues. MTT, wound healing, colony formation assays and western blot suggested that SSb2 inhibited MCF­7 proliferation and migration. It was further identified by western blot analysis that SSb2 treatment reduced levels of phosphorylated STAT3, VASP, matrix metallopeptidase (MMP) 2 and MMP9 in MCF­7 compared with the untreated cells. In addition, it was demonstrated that inhibition of STAT3 phosphorylation decreased VASP expression levels and induction of STAT3 phosphorylation increased VASP levels. Furthermore, it was observed that the treatment of Kunming mice with SSb2 at 30 mg/kg/day for 30 days induced no obvious changes in the liver or kidney tissues, as determined by haematoxylin and eosin staining. In conclusion, these results indicated that SSb2 may be a potential antitumor drug for the treatment of breast cancer, which acts by suppressing proliferation and migration by downregulating the STAT3 signalling pathway and inhibiting the expression of VASP, MMP2 and MMP9 expression.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Moléculas de Adesão Celular/genética , Proteínas dos Microfilamentos/genética , Ácido Oleanólico/análogos & derivados , Fosfoproteínas/genética , Fator de Transcrição STAT3/genética , Saponinas/farmacologia , Adolescente , Adulto , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Metaloproteinase 9 da Matriz/genética , Camundongos , Pessoa de Meia-Idade , Ácido Oleanólico/farmacologia , Adulto Jovem
10.
Org Lett ; 21(13): 5078-5081, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31199158

RESUMO

Catalytic ring opening of five- to eight-membered lactones with quinones is achieved through a redox chain mechanism. With low loading of a simple metal triflate Lewis acid catalyst and a chain initiator, C-H bonds of many quinones were efficiently functionalized with carboxylic acid-containing side chains. This method also features 100% atom economy and wide substrate scope. A novel route to the anti-asthma drug Seratrodast was developed. Mechanism study suggests that the redox chain reaction likely undergoes a carbocation intermediate.

11.
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
12.
Mol Immunol ; 101: 386-395, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30064075

RESUMO

OBJECTIVES: Indirubin (IR) is a bisindole compound extracted from the leaves of Chinese herb Indigo Naturalis. Indigo Naturalis has been widely used in traditional Chinese medicine to treat inflammatory and autoimmune diseases. Psoriasis is a chronic immune-mediated inflammatory skin disease in which γδ T cells play an important role. This study aims to determine the immunoregulatory effects and the underlying mechanisms of Indirubin in psoriasis-related inflammatory responses. METHODS: BALB/c mice with imiquimod (IMQ)-induced psoriasis-like dermatitis were treated with saline (Model), 1 mg/kg methotrexate (MTX) that serves as a positive control, or 12.5, 25 and 50 mg/kg Indirubin(IR) intragastrically. Keratinocytes proliferation, inflammatory cells infiltration, the expression of inflammatory cytokines and Jak/Stat pathway-related proteins in the skin lesion were examined. The abundance of γδ T cells in lymph nodes and spleen was determined by flow cytometry. The IL-17 expression and secretion, and the activation of Jak3/Stat3 pathways in in vitro cultured γδ T cell were tested. RESULTS: Indirubin ameliorated keratinocyte proliferation, reduced the infiltration of CD3+ T cells, IL-17 A-producing γδ T cells, and CD11b+ neutrophils, inhibited the mRNA expression of Il1, Il6, Il23, Il17a and Il22, and the protein expression of Jak/Stat pathway-related molecules in the skin lesion. Indirubin also reduced the abundance of γδ T cell and CCR6+ γδ T cells (the major IL-17 A producer) in spleen and lymph nodes. In cultured γδ T cells, Indirubin inhibited the mRNA expression of Il17a and Ifng, and the secretion of IL-17 A, while suppressed the activation of Jak3/Stat3 pathways. CONCLUSION: Indirubin alleviates IMQ-induced psoriasis-like dermatitis mainly through reducing the inflammatory responses mediated by IL-17 A-producing γδ T cells involving Jak3/Stat3 activation. Our results highlighted the novel mechanisms by which Indirubin ameliorates psoriasis-related inflammatory responses, supporting its therapeutic potential.


Assuntos
Imiquimode/efeitos adversos , Inflamação/patologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Pele/patologia , Células Th17/imunologia , Animais , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Mediadores da Inflamação/metabolismo , Interleucina-17/biossíntese , Janus Quinase 3/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Fosforilação/efeitos dos fármacos , Psoríase/induzido quimicamente , Psoríase/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
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
14.
Life Sci ; 207: 90-104, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29859222

RESUMO

AIMS: Psoriasis vulgaris is mediated by T and dendritic cells. This study aimed to investigate the effects of acetyl-11-keto-ß-boswellic acid (AKBA) on activated dendritic cells (DCs) using an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated with resiquimod (R848) in vitro. MATERIALS AND METHODS: The mice were treated with IMQ and intragastrically administered 25-100 mg/kg/day of AKBA, 1 mg/kg/day of methotrexate (MTX), or normal saline. The inflammation of skin lesions in IMQ mice were evaluated by psoriasis area and severity index (PASI) and pathological staining. The related proteins of Toll-like receptor (TLR)7/8 pathways were assessed using Western blotting, and the expression levels of interleukin (IL)-23 and IL-12p40 mRNA using reverse transcription-polymerase chain reaction. The numbers of DCs and marker-positive BMDCs were assessed using flow cytometry and the levels of inflammatory factors using the enzyme-linked immunosorbent assay. KEY FINDINGS: AKBA and MTX obviously improved the psoriasis-like skin lesions of IMQ-treated mice. AKBA also obviously decreased the PASI score, reduced the thickness of epidermis, ameliorated the infiltration of CD3+ and CD11c+ cells in skin lesions, decreased the activation of local DCs, inhibited the mRNA expression and secretion of inflammatory factors IL-12 and IL-23, inhibited the maturation and differentiation of DCs to promote T-cell differentiation, and inhibited the activation of TLR7/8 and IRF signaling pathways. SIGNIFICANCE: This study implied that AKBA might have an anti-inflammatory effect on psoriasis by inhibiting the maturation and activation of DCs via the TLR8 and IRF signaling pathways.


Assuntos
Citocinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Psoríase/tratamento farmacológico , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/metabolismo , Triterpenos/química , Aminoquinolinas , Animais , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular , Proliferação de Células , Técnicas de Cocultura , Células Dendríticas/metabolismo , Eritema/metabolismo , Imiquimode , Inflamação , Subunidade p35 da Interleucina-12/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , RNA Mensageiro/metabolismo , Transdução de Sinais , Baço/metabolismo
15.
Ultrastruct Pathol ; 42(1): 49-54, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29192840

RESUMO

The aim of this study is to investigate the effects of betulinic acid (BA) on triple-negative breast cancer MDA-MB-231 cells and observe the ultrastructural changes. The concentration of BA required to induce apoptosis in MDA-MB-231 cells has been previously reported. In this study, a cell counting kit-8 proliferation assay was used to measure cell viability and the apoptosis rate. Western blotting was performed to observe the protein expression levels of Bcl-2. Cell morphology and changes in cell density were observed by microscopy. Electron microscopy revealed pyknotic nuclei as well as vacuoles. Collectively, our results showed the morphological mechanisms by which BA impairs the ultrastructure of MDA-MB-231 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/patologia , Triterpenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Microscopia Eletrônica de Transmissão , Triterpenos Pentacíclicos
16.
Mol Med Rep ; 17(1): 1132-1140, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115535

RESUMO

Cardiomyocyte apoptosis is closely associated with the pathogenesis of heart failure. Jujuboside A (JUA) is a type of saponin isolated from the seeds of Zizyphus jujuba. In traditional Chinese medicine, it is believed that JUA possesses multiple biological effects, including antianxiety, antioxidant and anti­inflammatory activities. The present study aimed to evaluate the effects of JUA on norepinephrine (NE)­induced apoptosis of H9c2 cells and to investigate its underlying mechanisms. Rat H9c2 cardiomyocytes were pretreated with JUA and were then exposed to NE as an in vitro model of myocardial apoptosis. A cell viability assay, scanning electron microscopy, transmission electron microscopy, flow cytometry assay, acridine orange/ethidium bromide staining, reverse transcription­quantitative polymerase chain reaction and western blotting, all revealed that NE induced H9c2 cell apoptosis. The results demonstrated that NE inhibited cell viability, and enhanced cell damage and apoptosis of H9c2 cells. Conversely, pretreatment with JUA was able to reverse NE­induced decreased cell viability and increased apoptosis. Furthermore, JUA suppressed upregulation of the B­cell lymphoma 2 (Bcl­2)­associated X protein/Bcl­2 ratio, and inhibited the increased protein expression levels of cleaved caspase­3 and cleaved caspase­9 following NE exposure. However, the protein expression levels of cleaved caspase­12 and cleaved caspase­8 were not significantly altered following exposure to NE or JUA pretreatment. In addition, in JUA­pretreated cells, the protein expression levels of phosphorylated (p)­p38 and p­c­Jun N­terminal kinase were downregulated compared with in NE­treated cells. Furthermore, JUA regulated the activation of extracellular signal­regulated kinase (ERK) in NE­treated cells and significantly increased the expression levels of p­AKT. Taken together, these data suggested that JUA may protect against NE­induced apoptosis of cardiomyocytes via modulation of the mitogen­activated protein kinase and AKT signaling pathways. Therefore, JUA may be considered a potential therapeutic strategy for the treatment of heart disease.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Norepinefrina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo
17.
Mol Med Rep ; 16(6): 8307-8314, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28983593

RESUMO

Long­term glucocorticoid therapy results in various side effects, including a high incidence of glucocorticoid­induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis. Excess glucocorticoids reduce the viability of bone marrow­derived mesenchymal stem cells (BMSCs) and prolong osteoclast survival. These two types of cell are essential in the balance between bone formation and resorption. Tetramethylpyrazine (TMP), the pharmacologically active component extracted from Chuanxiong, has been reported to protect BMSCs from glucocorticoid­induced apoptosis. In the present study, the protective effects of TMP on BMSC differentiation and osteoclasts maturation in GIOP were investigated in vivo and in vitro. The immunostaining of osterix (OSX) and tartrate­resistant acid phosphatase (TRAP) staining indicated that TMP promoted osteogenesis and inhibited osteoclastogenesis in a rat model of GIOP. Treatment with 10­6 M dexamethasone (Dex) significantly inhibited BMSC differentiation and increased TRAP­positive cells in vitro. However, different concentrations of TMP (50, 100 and 200 µM) ameliorated the negative effects of Dex by promoting the activity of alkaline phosphatase (ALP) and the calcium mineralization of BMSCs following osteogenic induction, which increased the expression levels of osteogenic genes, including ALP, collagen type I α1, osteocalcin and OSX, and decreased osteoclastogenesis­related genes, including TRAP, nuclear factor of T­cells cytoplasmic 1 and cathepsin K. In addition, it was found that the inhibition of receptor activator of nuclear factor­κB ligand and intereleukin­6 in BMSCs may be a possible mechanism for the protective effects of TMP against glucocorticoid­induced osteoclastogenesis. These results are the first, to the best of our knowledge, to demonstrate that TMP promotes BMSC differentiation and inhibits osteoclastogenesis to ameliorate bone mass change in GIOP.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteogênese/efeitos dos fármacos , Pirazinas/farmacologia , Animais , Reabsorção Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Feminino , Interleucina-6/genética , Interleucina-6/metabolismo , Osteoclastos/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Ratos , Tomografia Computadorizada por Raios X
18.
Mol Med Rep ; 16(6): 8427-8433, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28983612

RESUMO

Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro­computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array­based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases­1 and monocyte chemotactic protein­1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.


Assuntos
Proteínas Sanguíneas , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/diagnóstico , Idoso , Animais , Biomarcadores , Diagnóstico Precoce , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Animais , Ovariectomia/efeitos adversos , Análise Serial de Proteínas , Ratos , Reprodutibilidade dos Testes , Microtomografia por Raio-X
19.
Ultrastruct Pathol ; 41(4): 284-290, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28691892

RESUMO

This paper explores the connection between paclitaxel, a chemotherapeutic agent, and gastric cancer cells. In this experiment, it is demonstrated that paclitaxel triggers autophagy and inhibits proliferation of gastric cancer cells. An 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect cell viability and the IC50 of paclitaxel. Western blot was used to detect the expression levels of P62, and to measure the protein expression of autophagy. Immunofluorescence was used to reveal the appearance of punctate structures in the cytoplasm-this ultrastructure associated with autophagy was observed by microscopy. Electron microscopy revealed the formation of double-membrane autophagosomes, a typical structure of autophagy. In conclusion, our research indicates that paclitaxel may influence gastric cancer BGC823 cells by way of inducing autophagy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Paclitaxel/farmacologia , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos
20.
Angew Chem Int Ed Engl ; 56(28): 8196-8200, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28544368

RESUMO

Allylation and benzylation of p-quinones was achieved through an unusual redox chain reaction. Mechanistic studies suggest that the existence of trace hydroquinone initiates a redox chain reaction that consists of a Lewis acid catalyzed Friedel-Crafts alkylation and a subsequent redox equilibrium that regenerates hydroquinone. The electrophiles could be various allylic and benzylic esters. The addition of Hantzsch ester as an initiator improves the efficiency of the reaction.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA