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1.
Food Funct ; 15(7): 3411-3419, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38470815

RESUMO

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1ß, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.


Assuntos
Lesão Pulmonar , NF-kappa B , Bifenil Polibromatos , Camundongos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Estresse Oxidativo , Apoptose , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Polifenóis/farmacologia , Chá , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/farmacologia
2.
Fish Shellfish Immunol ; 146: 109382, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242263

RESUMO

The extensive application of Tetrabromobisphenol A (TBBPA) leads to the pollution of part of the water environment and brings great safety risks to aquatic animals. As a natural extract, tea polyphenols (TPs) have antioxidant and anti-inflammatory effects. Gills are one of the immune organs of fish and constitute the first line of defense of the immune system. However, it was unclear whether TPs could mitigate TBBPA-induced gills injury. Therefore, an animal model was established to investigate the effect of TPs on TBBPA-induced gills. The results indicated that TBBPA changed the coefficient and tissue morphology of carp gills. In addition, TBBPA induced oxidative stress and inflammation, leading to ferroptosis and apoptosis in carp gills. Dietary addition of TPs significantly improved the antioxidant capacity of carp, effectively inhibited the overexpression of TLR4/NF-κB and its mediated inflammatory response. Moreover, TPs restored iron metabolism, reduced the expression of pro-apoptotic factors thereby alleviating ferroptosis and apoptosis in carp gills. This study enriched the protective effect of TPs and provided a new way to improve the innate immunity of carp.


Assuntos
Carpas , Ferroptose , Bifenil Polibromatos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Antioxidantes/metabolismo , Receptor 4 Toll-Like/genética , Carpas/metabolismo , Brânquias , Polifenóis/farmacologia , Polifenóis/metabolismo , Transdução de Sinais , Proteínas de Peixes , Inflamação/induzido quimicamente , Inflamação/veterinária , Inflamação/metabolismo , Apoptose , Chá/metabolismo
3.
Aquat Toxicol ; 265: 106780, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38041969

RESUMO

Microplastics (MPs) are widely distributed pollutants in the environment and accumulate in the aquatic environment due to human activities. Carp, a common edible aquatic organism, has been found to accumulate MPs in body. MicroRNA (miRNAs) is a non-coding short RNA that regulates protein expression by binding to target genes in various physiological processes such as proliferation, differentiation and apoptosis. The ovary is a crucial role in carp reproduction. In this study, we established a model of carp exposed to polyethylene microplastics (PE-MPs) in the aquatic environment to investigate the specific mechanism of PE-MPs causing ovarian injury and the involvement of miR-132/calpain (CAPN) axis. H&E stained sections revealed that PE-PMs induced inflammation in ovarian tissues and impaired oocyte development. TUNEL analysis showed an increased rate of apoptosis in ovarian cells treated with PE-PMs. RT-PCR and Western Blot assays confirmed that exposure to PE-MPs significantly decreased miR-132 expression while increasing CAPN expression at both mRNA and protein levels. The concentration of calcium ions was significantly increased in tissues, leading to CAPN enzyme activity increase. The expression of mitochondrial damage-related genes (bax, AIF, cyt-c, caspase-7, caspase-9, and caspase-3) was higher while the expression of anti-apoptotic genes (bcl-2 and bcl-xl) was lower. Protein levels of bax, AIF, caspase-3, bcl-2 and bcl-xl changed accordingly with the genetic alterations. Additionally, we discovered that PE-MPs can activate the p65 factor through the TRAF6/NF-kB pathway resulting in elevated production of pro-inflammatory factors IL-6, IL-1ß and TNF-a which contribute to ovarian inflammation development. This study investigates the impact of PE-MPs on carp ovarian function and provides insights into miRNAs' role and their target genes.


Assuntos
Carpas , MicroRNAs , Poluentes Químicos da Água , Animais , Feminino , Humanos , Microplásticos , Polietileno , Caspase 3/genética , Plásticos , Calpaína , Proteína X Associada a bcl-2 , Ovário , Poluentes Químicos da Água/toxicidade , Proteínas Proto-Oncogênicas c-bcl-2/genética , MicroRNAs/genética , Apoptose/genética , Inflamação/induzido quimicamente
4.
Cancer Med ; 12(23): 21129-21137, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37990780

RESUMO

OBJECTIVE: To compare the efficacy and safety of first-line anti-PD-1 combined with chemotherapy versus chemotherapy alone in patients with advanced urothelial carcinoma (UC). METHOD: Patients with advanced UC who received first-line treatment of chemotherapy (n = 51, gemcitabine/paclitaxel [albumin-bound] combined with platinum) or immunochemotherapy (n = 50, PD-1 inhibitors plus chemotherapy) were enrolled. The efficacy and safety were analyzed between the two groups. RESULTS: This study included data from 101 patients, including 51 patients in the chemotherapy group and 50 patients in the immunochemotherapy group. The median progression-free survival of the immunochemotherapy group was significantly longer than that of the chemotherapy group (11.5 vs. 7.17 m, HR = 0.56, p = 0.009). The two groups' overall survival showed no significant difference (20.3 vs. 17.8 m, p = 0.204). The objective response rates and the disease control rates of the two groups were 38.0% versus 49.0% (p = 0.26) and 88.0% versus 80.4% (p = 0.29). The incidence of adverse reactions (AEs) in the immunochemotherapy group and chemotherapy group were 90.0% and 84.3% (p = 0.394), respectively, and the incidence of Grade III-IV AEs were 32.0% and 35.3% (p = 0.726), respectively. CONCLUSION: In the first-line treatment of patients with advanced UC, anti-PD-1 therapy combined with chemotherapy might have better efficacy than chemotherapy alone, and AEs are similar between the two groups.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Paclitaxel/efeitos adversos , Desoxicitidina/efeitos adversos , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Oncol Lett ; 15(2): 1459-1468, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434837

RESUMO

To evaluate the prognostic significance of the altered expression of capicua transcriptional repressor (CIC) in isocitrate dehydrogenase (IDH)-mutant oligodendroglial tumors, a cohort of 54 IDH-mutant oligodendroglial tumors (designated as the Xijing cohort) were examined by immunohistochemistry (IHC), and two public expression data sets from The Cancer Genome Atlas (TCGA; n=265) and the Gene Expression Omnibus (GEO; n=45) were analyzed in the present study. The prognostic value was evaluated by survival analysis and Cox hazards models. Overall survival (OS) was investigated with Kaplan-Meier curves and log-rank tests. Gene set enrichment analysis (GSEA) was also performed to characterize the functional profiles of each subgroup. It was revealed that in IDH-mutant, 1p/19q co-deleted oligodendroglial tumors, higher CIC expression (at mRNA and protein levels) was associated with a more favorable OS time (log-rank P-values: TCGA, P=0.034; GEO, P=0.012; Xijing cohort, P=0.029). By contrast, among IDH-mutant, 1p/19q intact tumors, higher CIC expression was associated with poorer OS time (log-rank P-values: TCGA, P=0.007; GEO, P=0.017; Xijing cohort, P=0.012). To the best of our knowledge, this is the first study demonstrating the distinct prognostic value of altered CIC expression with regard to the 1p/19q status among IDH-mutant oligodendroglial tumors. The dual roles of CIC may be influenced by its transcriptional regulatory activity and the consequent functional profiles. Additionally, a simple risk classification scheme based on CIC expression alone is proposed for the optimal prediction of prognosis in patients with oligodendroglial tumors.

6.
Expert Opin Biol Ther ; 10(6): 927-36, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20415602

RESUMO

IMPORTANCE OF THE FIELD: Despite numerous advances made during the last decade in brain tumor therapy, the prognosis of glioblastoma has not improved and these tumors inevitably recur with no effective treatment. Thus, any new therapeutic strategy to target this most malignant tumor will be of significant benefit. RNAi is a powerful gene silencing method that might be used in combination with other agents to improve the efficacy of glioblastoma treatment. AREAS COVERED IN THIS REVIEW: Recent progress and challenges of pre-clinical and clinical research of RNAi therapy for glioblastoma. The review covers literature from 2003 to 2009. WHAT THE READER WILL GAIN: The principle of RNA interference therapy, three categories of RNAi triggers, different RNAi delivery system and pre-clinical and clinical studies that are currently underway to evaluate the validity of RNAi as a potential therapeutic strategy against glioblastoma are discussed. TAKE HOME MESSAGE: RNA inference therapy combined with other therapeutics may offer therapeutic potential for glioblastoma multiforme. Further studies are required to develop more efficient and specific delivery systems, select suitable gene targets, optimize treatment dose and administration schedule, evaluate the efficacy of combination treatment strategies, establish a validated clinical response measure system etc.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Interferência de RNA , RNA Interferente Pequeno/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Sistemas de Liberação de Medicamentos , Humanos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/efeitos adversos
7.
Cancer Biol Ther ; 8(11): 1018-23, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19421009

RESUMO

The leucine-rich and immunoglobulin-like domains (LRIG) gene family contains LRIG1, 2 and 3. LRIG1 is a negative regulator of EGFR, but little is known about the function of LRIG2. To determine the role of LRIG2 in the progression of glioma, we performed RNA interference-mediated knockdown of LRIG2 in a human glioma cell line (GL15). Downregulation of LRIG2 expression resulted in: rapid EGF-mediated loss of EGFR; decreased proliferation; G(0)/G(1) arrest; increased spontaneous apoptosis; enhanced cell adhesion and increased invasion capability of GL15 cells in vitro. These findings indicate that LRIG2 possesses distinct functions compared with LRIG1 and validate the attractiveness of LRIG2 as a target in glioma therapy.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Glioblastoma/genética , Glicoproteínas de Membrana/genética , RNA Interferente Pequeno/genética , Apoptose/genética , Adesão Celular/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/patologia , Regulação para Baixo , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/biossíntese , Receptores ErbB/genética , Glioblastoma/patologia , Humanos , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/deficiência , Interferência de RNA , RNA Neoplásico/genética , Transfecção
8.
Cancer Lett ; 278(1): 104-12, 2009 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-19200647

RESUMO

LRIG3 (leucine-rich repeats and immunoglobulin-like domains, LRIG) gene is both under-and over-expressed in human cancers and its role on tumor growth is not fully clarified. Here, we used a human U6 promoter-driven DNA template approach to induce short hairpin RNA (shRNA)-triggered RNA interference (RNAi) to block LRIG3 gene expression in the human glioma cell line GL15. Specific knockdown of LRIG3 by shRNA resulted in significantly increase of the GL15 invasion and adhesion activity in vitro and markedly promoted cell growth. LRIG3 repression also induced increment of the proportion of G0/G1 cells and inhibited apoptosis in GL15 cells. Our results demonstrated that RNAi against LRIG3 could effectively down regulate LRIG3 gene expression. LRIG3 might be involved in the regulation of EGFR signaling, and serve as a tumor suppressor gene in the pathogenesis of glioma.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Glioma/genética , Proteínas de Membrana/genética , Interferência de RNA , Apoptose/genética , Adesão Celular , Ciclo Celular/genética , Divisão Celular/genética , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/patologia , Receptores ErbB/fisiologia , Glioblastoma/genética , Glioblastoma/patologia , Glioma/patologia , Humanos , Invasividade Neoplásica , Regiões Promotoras Genéticas , RNA Neoplásico/genética , Transdução de Sinais/genética
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