Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.481.859
Filtrar
1.
Gene ; 766: 145113, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32891771

RESUMEN

Breast cancer remains the most common malignancy in women worldwide. Circular RNAs (circRNAs) are a newly validated type of endogenous non-coding RNAs and accumulating evidence suggests that aberrant circRNAs are involved in disease pathogenesis. However, the function of circRNAs in breast cancer remains largely unknown. This study is aimed to characterize the potential role and mechanism of hsa_circ_0000442 (circ_0000442) in breast cancer. The human breast epithelial cell line (MCF-10A), breast cancer cell lines (MCF-7, T47D, BT474, SK-BR-3, MDA-MB-231, SUM-1315) and the Balb/C Nude mice were used for exploration, and the qRT-PCR, western blot, dual-luciferase reporter assay, glo assay, colony formation assay, and tumor xenograft were carried out for investigation. In this study, the results showed a lower expression of circ_0000442 in breast cancer tumor tissues compared with the adjacent normal tissues. Subsequently, circ_0000442 was found to acted as the sponge of miR-148b-3p in breast cancer cells, thus exerting the tumor-suppressive effects. In the subsequent mechanism study, results showed that miR-148b-3p directly targeted PTEN, a well-known tumor suppressor which negatively regulats PI3K/Akt pathway, thus promoting tumor growth in breast cancer. Overall, this study for the first time identified the tumor-suppressive role of circ_0000442 in breast cancer and found PTEN as a novel direct target of miR-148b-3p. The regulatory role of circ_0000442/miR-148b-3p/PTEN/PI3K/Akt axis was preliminarily confirmed in breast cancer cells and mouse models. These findings suggest an important progress in our standing of breast cancer and lay the foundation for the further function, diagnosis, therapy and prognosis research of circular RNAs in breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Circular/genética , Transducción de Señal/genética , Animales , Línea Celular , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Pronóstico
2.
Gene ; 766: 145134, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32898605

RESUMEN

BACKGROUND: Artesunate (ART) has been used extensively as anti-malarial drugs worldwide. Besides, it has also been reported to have anti-cancer activities. This study was aimed to explore the anti-cancer activity of ART in combination with cisplatin (CIS) on A549 cells. METHODS: Cells were cultured with different concentrations of ART and/or CIS for 24, 48, or 72 h to test the anti-proliferative effects by CCK-8 assay. Colony formation assay and EdU staining were also performed. TUNEL staining was used to illustrate the morphologic changes. Cell cycle and apoptosis were determined by flow cytometry assay, and Western blot analysis was conducted to detect the expression of apoptosis- and proliferation-related proteins. Caspase activities were determined by colorimetric assay kit. Moreover, the synergistic effect of ART with CIS in A549 cell xenograft model was also determined. RESULTS: ART significantly inhibited cell proliferation in dose- and time-dependent manners. Collectively, the combination treatment remarkably decreased colony formation rates and increased the rates of TUNEL-positive cells compared with mono-treatment. Mechanistically, the combination treatment influenced the expression of Bcl-2, Bax, p-P53, Caspase-3/7, Caspase-9, CyclinB1, P34, P21, and synergistically regulated the activity of P38/JNK/ERK1/2 MAPK pathway. In mice A549 xenograft tumors, the combination strategy significantly increased the anti-cancer efficacy of ART and CIS alone, consistent with the in vitro observations. CONCLUSIONS: ART exhibited significant anti-tumor effect on A549 cells and this efficiency could be enhanced by combination with CIS.


Asunto(s)
Antineoplásicos/farmacología , Artesunato/farmacología , Cisplatino/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células A549 , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Desnudos , Inhibidores de Proteínas Quinasas/farmacología
3.
Gene ; 766: 145150, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32949695

RESUMEN

There are a few studies indicating that small molecular compounds affect the proliferation, differentiation, apoptosis, and autophagy of female germline stem cells (FGSCs). However, whether small molecular compound 28 (C28) affect development of FGSCs remains unknown. In this study, we found that C28 reduced the viability and proliferation of FGSCs, respectively. Additionally, western blotting showed that the expression of autophagy marker light chain 3 beta II (LC3B-II) was significantly increased and expression of sequestosome-1 (SQSTM1) was significantly reduced in C28-treated groups. Immunofluorescence showed that, in C28-treated groups, the number of LC3B-II-positive puncta was increased significantly. These results indicated that C28 induced autophagy of FGSCs in vitro. Furthermore, data from Chromatin Immunoprecipitation Sequencing for H3K27ac showed that autophagy-related biological processes such as regulation of mitochondrial membrane potential, Golgi vesicle transport, and cellular response to reactive oxygen species were different after C28-treated. In addition, RNA-Seq showed that the expression of genes (Trib3, DDIT3, and ATF4) related to endoplasmic reticulum (ER) stress was enhanced by C28. These results suggest that the changes of H3K27ac and ER stress might be associated with C28-induced FGSC autophagy.


Asunto(s)
Acetilación/efectos de los fármacos , Autofagia/efectos de los fármacos , Histonas/genética , Células Madre Oogoniales/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Transcriptoma/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Femenino , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Células Madre Oogoniales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
4.
Gene ; 766: 145153, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32950633

RESUMEN

AIM: Acute lung injury (ALI) is the mild form of acute respiratory distress syndrome (ARDS) which is a common lung disease with a high incidence and mortality rate. Recent studies manifested that some circular RNAs were associated with ALI. In this study, we aimed to uncover the effect of circular RNA circ_0054633 on ALI initiation and progression and proposed a new mechanism related to ALI. METHODS: The lipopolysaccharides (LPS)-induced acute lung injury model were build both in vivo of rat and in vitro of primary murine pulmonary microvascular endothelial cells (MPVECs). Hematoxylin and eosin (H&E) was employed to observe the tissue morphology and estimate the degree of lung damage. We used real-time quantitative polymerase chain reaction (RT-qPCR) to measure the expression level of circ_0054633. The expression levels of inflammatory cytokines IL-17A and tumor necrosis factor-α (TNF-α) were detected by ELISA. The effects of circ_0054633 on MPVECs proliferation and apoptosis were detected with the help of CCK-8 and apoptosis assay, separately. The expression level of NF-κB p65 protein was measured by Western blot. RESULTS: circ_0054633, IL-17A, TNF-α and NF-κB p65 were all overexpressed in LPS-treated rat and MPVECs, and LPS enhanced the proliferation and apoptosis of MPVECs. While circ_0054633 silencing reversed the above promotion effects of LPS on IL-17A, TNF-α expression and MPVECs proliferation and apoptosis. CONCLUSIONS: Quietness of circ_0054633 alleviated LPS-induced ALI via NF-κB signaling pathway, implicating circ_0054633 may be a potential biomarker for diagnose and therapy of ALI.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Proliferación Celular/fisiología , Células Endoteliales/metabolismo , Inflamación/metabolismo , FN-kappa B/metabolismo , ARN Circular/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Inflamación/inducido químicamente , Interleucina-17/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
5.
Gene ; 766: 145152, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32979431

RESUMEN

OBJECTIVE: Cerebrovascular disease is one of the major diseases that seriously harm human health currently. The purpose of this study is to find an effective treatment and clarify its mechanism of action to provide a new idea and drug target for the clinical treatment of ischemic cerebrovascular disease. METHODS: The microglia cell line (BV2 cell line) was cultured in vitro. Prepare a hypoxia ischemia cell model by OGD and simulate the pathophysiological process of ischemic cerebrovascular disease in vivo. According to the techniques of LDH Cytotoxicity Assay Kit, flow cytometry of Annexin V-FITC Apoptosis Detection Kit, Laser Confocal Fluorescence Immunostaining (Double staining method), enzyme-linked immunosorbent assay (ELISA), and Western blotting, BV2 cells are observed through morphology and function changes induced by OGD. Moreover, these techniques were used to analyze changes in key proteins expression of signal transduction pathway in ischemic cerebrovascular disease, to explore the mechanism of gastrodin on ischemic cerebrovascular disease, and to elucidate the available ways for cell protection following ischemia and hypoxia. RESULTS: Gastrodin has no obvious toxic effect on BV-2 cells under physiological conditions. The death rate of BV-2 cells increases as the time of hypoxia increase. In the absence of oxygen, Gastrodin has a protective effect on the survival of BV-2 cells. This protective effect is related to the reduction of apoptosis rate. It can also improve the hypoxic tolerance of BV-2 cells, and there is no obvious Gastrodin dose-dependence. Moreover, Gastrodin has dual effects on BV-2 cells. The dual role of Gastrodin is closely related to the expression of several proteins which can affect the MAPK signal transduction pathway. CONCLUSION: Gastrodin has a dual effect on microglia with OGD. On the one hand, Gastrodin can inhibit the inflammatory cytokines secreted by microglia and aggravate the inflammatory response; on the other hand, Gastrodin can promote the secretion of protective cytokines from microglia to reduce the inflammatory response.


Asunto(s)
Alcoholes Bencílicos/farmacología , Glucosa/metabolismo , Glucósidos/farmacología , Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Ratones , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuroprotección/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
6.
Food Chem ; 334: 127475, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32688176

RESUMEN

Although numerous types of organisms have been used to enrich selenium, a low-cost and efficient organism is yet to be identified. This study aimed to develop a new means of selenium enrichment using Tenebrio molitor larvae. Our results indicated that the total selenium content in larvae was increased 83-fold to 54.21 ± 1.25 µg/g, and of this content, organic selenium accounted for over 97% after feeding the larvae with 20 µg/g of sodium selenite. Selenium was distributed unequally in the protein fraction with following order: alkali-soluble protein-bound selenium (36.32%) > salt-soluble protein-bound selenium (19.41%) > water-soluble protein-bound selenium (17.03%) > alcohol-soluble protein-bound selenium (3.21%). Additionally, 81% of the selenium within the soluble proteins was distributed in subunits possessing molecular weights of <40 kDa. After hydrolysis by alcalase, the protein hydrolysate of selenium-enriched larvae possessing 75% selenium recovery exhibited stronger antioxidant and immunoregulatory activities than those of regular larvae.


Asunto(s)
Antioxidantes/farmacología , Factores Inmunológicos/farmacología , Proteínas de Insectos/metabolismo , Hidrolisados de Proteína/farmacología , Selenio/farmacocinética , Tenebrio/metabolismo , Adulto , Aminoácidos/análisis , Aminoácidos/metabolismo , Animales , Antioxidantes/metabolismo , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Hidrólisis , Factores Inmunológicos/metabolismo , Proteínas de Insectos/farmacología , Larva/efectos de los fármacos , Larva/metabolismo , Ratones , Hidrolisados de Proteína/metabolismo , Células RAW 264.7 , Selenio/análisis , Subtilisinas/química , Subtilisinas/metabolismo , Tenebrio/efectos de los fármacos
7.
Gene ; 766: 145022, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32758579

RESUMEN

BACKGROUND: A better understanding of the mechanism(s) underlying cardioembolic stroke can promote recovery and reduce the risk of recurrent embolisms. METHODS: Peripheral blood mononuclear cell (PBMC) gene expression datasets from cardioembolic patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database (GSE58294). The Limma software package was utilized to identify differentially-expressed genes (DEGs). Protein-protein interaction (PPI) analysis of the DEGs was performed using STRING. A weighted gene co-expression network analysis (WGCNA) was used to build a gene co-expression network. In vitro experiments assessed the effects on neutrophils exposed to oxygen and glucose-deprived (OGD) cortical neurons. An in vivo murine model of thromboembolic stroke was constructed through thrombin injection to examine effects on circulating neutrophils. Mechanistic in vitro studies were conducted using the proteasome inhibitor MG132, the p53-Mdm2 binding inhibitor Nutlin-3a, Mdm2 small-interfering RNA (siRNA), and Ctnnb1 siRNA. RESULTS: DEG analysis identified 44 upregulated and 66 downregulated genes in cardioembolic stroke PBMCs. PPI analysis of these DEGs yielded one eight-node protein module with ß-catenin (CTNNB1) as the central hub protein. Integration of the DEGs with WGCNA-derived hub genes revealed the key hub DEGs CTNNB1 and mouse double minute 2 (MDM2). Follow-up experiments revealed Mdm2, p53, and phospho-ß-catenin upregulation in neutrophils exposed to OGD neurons in vitro and following thromboembolic stroke in vivo. Mechanistic studies revealed that neutrophils transcriptionally upregulate Ctnnb1 expression to compensate for Mdm2/p53-mediated ß-catenin degradation induced by exposure to OGD neurons, thereby promoting neutrophil survival. CONCLUSION: Compensatory Ctnnb1 transcriptional upregulation in neutrophils induced by ischemic neuron exposure may be involved in promoting neutrophil survival following cardioembolic stroke.


Asunto(s)
Neutrófilos/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/metabolismo , Proteína p53 Supresora de Tumor/genética , Regulación hacia Arriba/genética , beta Catenina/genética , Animales , Células Cultivadas , Regulación hacia Abajo/genética , Expresión Génica/genética , Redes Reguladoras de Genes/genética , Corazón/fisiopatología , Humanos , Leucocitos Mononucleares/metabolismo , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Transcripción Genética/genética , Activación Transcripcional/genética
8.
Gene ; 766: 145032, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32771387

RESUMEN

Control of gene expression by epigenetic regulators is fundamental to tissue development and homeostasis. Loss-of-function (LOF) studies using siRNAs for epigenetic regulators require that RNA interference rapidly reduces the cellular levels of the corresponding mRNAs and/or proteins. The most abundant chromatin structural proteins (i.e., the core histones H2A, H2B, H3 and H4) have relatively long half-lives and do not turn over rapidly, although their mRNAs are labile. The question arises whether epigenetic regulatory enzymes (e.g., Ezh2) or proteins that interact with histones via selective modifications (e.g., Cbx1 to Cbx8, Brd4) are stable or unstable. Therefore, we performed classical α-amanitin and cycloheximide inhibition assays that block, respectively, mRNA transcription and protein translation in mouse MC3T3 osteoblasts, ATDC5 chondrocytes and C2C12 myoblasts. We find that mRNA levels of Cbx proteins and Ezh2 were significantly depleted after 24 hrs, while their corresponding proteins remained relatively stable. As positive control, the half-life of the labile cyclin D1 protein was found to be less than 1 hr. Our study suggests that histone code readers and writers are relatively stable chromatin-related proteins, which is consistent with their long-term activities in maintaining chromatin organization and phenotype identity. These findings have conceptual ramifications for the interpretation of RNAi experiments that reduce the mRNA but not protein levels of epiregulatory proteins. We propose that siRNAs for at least some epigenetic regulatory proteins may exert their biological effects by blocking translation and new protein synthesis rather than by decreasing pre-existing protein pools.


Asunto(s)
Epigénesis Genética/genética , Sistema Musculoesquelético/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células 3T3 , Animales , Línea Celular , Cromatina/genética , Epigenómica/métodos , Histonas/genética , Ratones , Biosíntesis de Proteínas/genética , Estabilidad Proteica , Transcripción Genética/genética
9.
Food Chem ; 335: 127649, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32738538

RESUMEN

Rosa rugosa Thunb. seed oil (RR) extracted by supercritical CO2 was investigated. RR chemical composition, radical scavenging effect and oxidative stability were evaluated. RR aqueous emulsions were examined for cell cytotoxicity, proliferation, redox state and migration using mouse embryonic fibroblast Balb/3T3, human dermal fibroblast NHDF cell lines, and on neoplastic cell lines: acute monocytic leukemia THP-1 and lung adenocarcinoma A549. RR total contents of phytosterols, tocopherols, carotenoids and phenolics were 10115.23, 784.16, 40.32 and 10.30 mg/kg, respectively. Rich antioxidant composition of RR was reflected in its high antioxidant activity (2.1 mM/kg Trolox equivalent) as well as oxidative stability (activation energy 105.6 kJ/mol). The RR emulsions led to marked augmentation of the total cell protein content in BALB/3T3 and NHDF cultures, inhibited cancer cell migration and reduced ROS formation. The studied RR oil proved to have a remarkable combination of bioactive compounds and to exert an antioxidative and chemopreventive effects.


Asunto(s)
Aceites Vegetales/química , Aceites Vegetales/farmacología , Rosa/química , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Dióxido de Carbono/química , Carotenoides/química , Carotenoides/aislamiento & purificación , Carotenoides/farmacología , Línea Celular , Cromatografía con Fluido Supercrítico , Humanos , Ratones , Oxidación-Reducción , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Fitosteroles/química , Fitosteroles/aislamiento & purificación , Fitosteroles/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Aceites Vegetales/aislamiento & purificación , Semillas/química , Tocoferoles/química , Tocoferoles/aislamiento & purificación , Tocoferoles/farmacología
10.
Sci Total Environ ; 752: 141784, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32889265

RESUMEN

Emerging evidence suggests that perinatal dioxin exposure affects neurodevelopment and impairs multiple brain functions, including cognitive, language, learning and emotion, in the offspring. However, the impacts of gestational and lactational exposure to dioxin on behavior and related molecular events are still not fully understood. In this study, female C57BL/6J mice were orally administered three doses of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1 or 10 µg/kg body weight (bw)) during the pregnancy and lactation periods. The locomotion, exploration and anxiety-related behaviors were examined by an open field test of the young adult female offspring at postnatal day 68. We found that the maternal TCDD exposure, particularly at a low dose, increased movement ability, novelty-exploration and certain anxiety-related behaviors in the offspring. Such hyperactivity-like behaviors were accompanied by the upregulation of certain genes associated with cholinergic neurotransmission or synaptogenesis in the offspring brain. In accordance with the potential enhancement of cholinergic neurotransmission due to the gene upregulations, the enzymatic activity of acetylcholinesterase was decreased, which might lead to excess acetylcholine and consequent hyper-excitation at the synapses. Thus, we found that gestational and lactational TCDD exposure at low dose caused hyperactivity-like behaviors in young adult female offspring and speculated the enhancement of cholinergic neurotransmission and synaptogenesis as potential molecular events underlying the neurobehavioral effects.


Asunto(s)
Dibenzodioxinas Policloradas , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Humanos , Lactancia , Exposición Materna/efectos adversos , Ratones , Ratones Endogámicos C57BL , Dibenzodioxinas Policloradas/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente
11.
Sci Total Environ ; 753: 141871, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-32891997

RESUMEN

Arsenic is a global pollutant that can accumulate in rice and has been confirmed to disturb the gut microbiome. By contrast, the influence on the gut mycobiome is seldom concerned because fungi comprise a numerically small proportion of the whole gut microcommunity. To expand the detection of the mycobiome in different gut sections of mammals and investigate the influence of food arsenic on the gut mycobiome in the digestive tract, we treated mice with feeds containing different compositions of arsenic species (7.3% sodium arsenate, 72.7% sodium arsenite, 1.0% sodium monomethylarsonate, and 19.0% sodium dimethylarsinate) in rice at a total arsenic dose of 30 mg/kg. After 60 days of exposure, the feces of four different sites, the ileum, cecum, colon, and excreted feces, were collected and analyzed by internal transcribed spacer gene sequencing. Among the samples, the major fungal phyla were Ascomycota, Basidiomycota, and Zygomycota; the top 10 fungal genera were Aspergillus, Verticillium, Penicillium, Cladosporium, Alternaria, Fusarium, Ophiocordyceps, Trametes, Mucor, and Nigrospora. In control mice, along the murine digestive tract, the mycobial richness and composition were significantly changed; Aspergillus and Penicillium possessed the higher ability to be stabilized in the murine gut, and larger proportions of positive correlations were observed among the major fungi. After arsenic exposure, the fungal composition was more disturbed in the intestinal tract than in feces. Along the digestive tract, arsenic can trigger larger mycobial variations, and the sensitivities of major fungi to arsenic were changed. Thus, the murine intestinal spatial mycobiota are more perturbed than excreted fecal mycobiota after food arsenic exposure. Feces are insufficient to be selected as a representative of the gut mycobiota in arsenic exposure studies.


Asunto(s)
Arsénico , Micobioma , Animales , Heces , Hongos , Intestinos , Ratones , Trametes
12.
Sci Total Environ ; 753: 141949, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-32891999

RESUMEN

Bisphenol S (BPS) is the major substitute for the production of bisphenol A (BPA)-free products and detected in both food and environment. Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted, the potential influence of BPS is not fully understood. Herein, a non-targeted lipidomic study was performed to explore BPA/BPS exposure actions using the 3T3-L1 preadipocyte differentiation model, and revealed the comprehensive lipidome disturbance induced by either BPA or BPS exposure at different doses of 0.01, 1 and 100 µM. BPA was more potent than BPS in disturbance of lipid metabolism. A considerable similarity of BPS exposure to BPA was discovered. The key lipid remodeling in response to exposure was found to involve the cardiolipins, phosphatidylglycerols and fatty acids metabolic pathways, providing novel clues of potential mechanism in which both BPA and BPS exposure could be associated with increased risk of insulin resistance. Our study supplies the perspective into the lipidome response to environmental stress induced by BPA/BPS, and shows that BPA-free products are not necessarily safer. Substitution of BPA by its structural analog BPS should be therefore performed with caution.


Asunto(s)
Compuestos de Bencidrilo , Lipidómica , Animales , Compuestos de Bencidrilo/toxicidad , Ratones , Fenoles/toxicidad , Sulfonas
13.
Food Chem ; 336: 127744, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32781352

RESUMEN

Cardoon (Cynara cardunculus L.) bracts were collected at different maturation stages to investigate seasonal changes in the phenolic compounds profile and in vitro bioactivities. Among the 12 phenolic compounds tentatively identified, 3,5-O-dicaffeoylquinic acid (21.83 mg/g extract) and apigenin-7-O-glucuronide (10.6 mg/g extract) were the most abundant. Immature bracts (C1: principal growth stage (PGS) 5) had the highest phenolic compounds content, and anti-inflammatory (IC50 = 72 µg/mL) and cytotoxic (GI50 of 30-79 µg/mL) activities. Moreover, extract C1 inhibited efficiently the formation of thiobarbituric acid reactive substances (TBARS; IC50 = 26.8 µg/mL), while extract C8 (PGS 8/9) was more effective against oxidative haemolysis (IC50 38 and 75 µg/mL). The highest antibacterial and antifungal activities were attributed to samples C1 and C6 (PGS 7/8) and samples C2 (PGS 5/6) and C4 (PGS 6/7), respectively. Overall, the obtained results suggest the seasonal changes of polyphenolic composition and bioactivity of cardoon bracts of variable maturity.


Asunto(s)
Cynara/química , Fenoles/química , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cynara/crecimiento & desarrollo , Cynara/metabolismo , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Fenoles/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Células RAW 264.7 , Estaciones del Año
14.
Gene ; 764: 145080, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32858178

RESUMEN

Spermatocyte (spc) formation from spermatogonia (spg) differentiation is the first step of spermatogenesis which produces prodigious spermatozoa for a lifetime. After decades of studies, several factors involved in the functioning of a mouse were discovered both inside and outside spg. Considering the peculiar expression and working pattern of each factor, this review divides the whole conversion of spg to spc into four consecutive development processes with a focus on extracellular cues and downstream transcription network in each one. Potential coordination among Dmrt1, Sohlh1/2 and BMP families mediates Ngn3 upregulation, which marks progenitor spg, with other changes. After that, retinoic acid (RA), as a master regulator, promotes A1 spg formation with its helpers and Sall4. A1-to-B spg transition is under the control of Kitl and impulsive RA signaling together with early and late transcription factors Stra8 and Dmrt6. Finally, RA and its responsive effectors conduct the entry into meiosis. The systematic transcription network from outside to inside still needs research to supplement or settle the controversials in each process. As a step further ahead, this review provides possible drug targets for infertility therapy by cross-linking humans and mouse model.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Espermatocitos/fisiología , Espermatogénesis/genética , Espermatogonias/fisiología , Animales , Proteínas Morfogenéticas Óseas/metabolismo , Autorrenovación de las Células/genética , Humanos , Masculino , Ratones , Túbulos Seminíferos/citología , Túbulos Seminíferos/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Transcripción Genética , Tretinoina/metabolismo , Regulación hacia Arriba
15.
Gene ; 764: 145100, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32877748

RESUMEN

Adipocyte differentiation is an essential part of adipose tissue development, and is closely related to obesity and obesity-related diseases. In this study, we found that the expression of PPARγ, RUVBL2 and Adiponectin were concurrently obviously increased in the 5th-7th day of 3T3-L1 cell differentiation. PPARγ overexpression or the PPARγ activator facilitated Adiponectin trafficking and secretion and upregulated RUVBL2 expression as well as AS160 phosphorylation during adipogenic differentiation of 3T3-L1 cells. Consistently RUVBL2 overexpression also enhanced the polymerization and secretion of Adiponectin, in contrast, RUVBL2 knockdown reduced Adiponectin secretion. Further, PPARγ significantly enhanced RUVBL2 promoter activity and transcription. The progressive deletions and mutations of RUVBL2 promoter for PPARγ binding sites suggested that the PPARγ binding motif situated at -804/-781 bp is an essential component required for RUVBL2 promoter activity. Chromatin immunoprecipitation (ChIP) assays determined that PPARγ can directly interact with the RUVBL2 promoter DNA. Taken together, these data suggest that PPARγ promotes the expression, polymerization and secretion of Adiponectin by activating RUVBL2 transcriptionally, which accelerates 3T3-L1 cell differentiation.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/genética , Adipocitos/fisiología , Adipogénesis/genética , Adiponectina/metabolismo , ADN Helicasas/genética , PPAR gamma/metabolismo , Células 3T3-L1 , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Animales , Sitios de Unión/genética , Diferenciación Celular/genética , Inmunoprecipitación de Cromatina , Clonación Molecular , ADN Helicasas/metabolismo , Ratones , Mutación , Regiones Promotoras Genéticas/genética , Multimerización de Proteína/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Activación Transcripcional , Regulación hacia Arriba
16.
Sci Total Environ ; 751: 141734, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32882555

RESUMEN

We estimated associations between ambient air pollution, home environment and asthma as well as rhinitis among adults across China. A total of 40,279 young adults from eight Chinese cities participated in a questionnaire survey (participation rate 75%). There were questions on health and home environment. Information on city level gross domestic product (GDP) per capita, ambient temperature and PM10 and NO2 were collected from registers. Two-level logistic regression models were used to study health associations. Totally 1.6% reported asthma and 6.6% reported allergic rhinitis (AR). Higher temperature was associated with more asthma but less AR. Higher GDP was associated with less asthma but more AR. Higher degree of urbanization, higher level of NO2 and living near heavily trafficked road were risk factors for asthma and AR. Participants in older buildings reported more asthma. Redecoration and buying new furniture were related to more asthma and AR (OR = 1.15-1.91). Using natural gas (OR = 1.34) and biomass (OR = 1.35) for cooking were risk factors for AR. Burning mosquito coils and incense increased the risk of asthma and AR. Cat keeping (OR = 2.88), dog keeping (OR = 2.04), cockroaches (OR = 1.54) and rats or mice (OR = 1.46) were associated with asthma. Cockroaches increased the risk of AR (OR = 1.22). Air humidifier and air cleaner were linked to asthma and AR. Frequent cleaning and exposing bedding to sunshine were protective. In conclusion, urbanization, NO2 and traffic exhaust can increase the risk of adult asthma and AR. Higher ambient temperature was related to more asthma but less AR. Indoor animals such as cats, dogs, rats/mice and presence of cockroaches were associated with asthma or AR. Indoor chemical sources such as redecoration and new furniture were other risk factors. Cooking with natural gas or biomass and burning mosquito coils and incense were associated with asthma or AR. Frequent cleaning and exposing bedding to sunshine were protective.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Asma , Rinitis Alérgica , Anciano , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Animales , Asma/epidemiología , Gatos , China/epidemiología , Ciudades , Perros , Humanos , Ratones , Ratas , Rinitis Alérgica/epidemiología , Factores de Riesgo , Adulto Joven
17.
Food Chem ; 336: 127539, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32763730

RESUMEN

Hesperidin hydrolysates (HHS) was produced by the hydrolysis of hesperidin (HDN) in previous studies. The potential components in HHS were identified by LC-MS, and minor components (MCS) in HHS were isolated. Antioxidant activities by radical-scavenging capacities, reducing capacity and ß-carotene-linoleate assay, anti-inflammatory effects by inhibiting NO production of RAW 264.7 cells, and α-glucosidase inhibitory effects of HDN, HHS, MCS and henperetin (HTN) were investigated in present study. HHS showed higher radical scavenging activities, higher reducing capacity, and higher inhibitory activity in the ß-carotene-linoleate assay than HDN. HHS inhibited the production of NO and pro-inflammatory cytokines of RAW 264.7 cells more strongly than HDN. HHS also intensively inhibited α-glucosidase activity whereas HDN showed little activity. In addition, the effects of MCS on above activities showed it play a synergistic part with HTN. This work suggested that hydrolyzation of HDN enhance the activities, and provided valuable information on effective utilization of HDN.


Asunto(s)
Antiinflamatorios/química , Antioxidantes/química , Citrus/química , Inhibidores Enzimáticos/química , Hesperidina/análisis , Animales , Antiinflamatorios/farmacología , Catálisis , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Citrus/metabolismo , Inhibidores Enzimáticos/metabolismo , Hesperidina/metabolismo , Hesperidina/farmacología , Hidrólisis , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectrometría de Masas , Ratones , Óxido Nítrico/metabolismo , Células RAW 264.7 , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismo
18.
Gene ; 764: 145106, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32889059

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) are a new class of non-coding RNA with a stable structure formed by special loop splicing. Research increasingly suggests that circRNAs play a vital role in the pathogenesis and progression of various diseases. However, the roles of circRNAs in osteoblast differentiation under microgravity remain largely unknown. Here, we investigated the roles and mechanobiological response of circRNAs in osteoblasts under simulated microgravity. METHODS: Differential circRNA and mRNA expression profiles of MC3T3-E1 cells during exposure to microgravity were screened by RNA transcriptome sequencing technology (RNA-seq). The selected RNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied for gene function analyses. RESULTS: A total of 427 circRNAs and 1912 mRNAs were differentially expressed along with osteogenic differentiation in the simulated microgravity group (SMG) compared to the control group (CON). Of these, 232 circRNAs and 991 mRNAs were upregulated, whereas 95 circRNAs and 921 mRNAs were downregulated (fold change ≥ 2, p < 0.05). The results showed that the parental genes of circRNAs and mRNAs were mainly enriched in anatomical structure morphogenesis, anchoring junction and protein binding. KEGG analysis results showed that the differentially expressed mRNAs were enriched in the regulation of the actin cytoskeleton, focal adhesion, and Ras signalling pathway. Subsequently, 9 core regulatory genes, including 6 mRNAs and 3 circRNAs, were identified based on their possible function in osteoblast differentiation. Based on this analysis, circ_014154 was selected as the target circRNA, which likely plays important roles in osteogenic differentiation processes under microgravity. The circRNA-miRNA-mRNA network showed that circRNAs might act as miRNA sponges to regulate osteoblast differentiation. CONCLUSION: By presenting a better understanding of the molecular mechanisms of genes and circRNAs in simulated microgravity, the present study will provide a novel view of circRNAs in the regulation of osteogenic differentiation and bone formation.


Asunto(s)
Diferenciación Celular/genética , Osteoblastos/fisiología , Osteogénesis/genética , ARN Circular/metabolismo , Simulación de Ingravidez/efectos adversos , Animales , Línea Celular , Biología Computacional , Conjuntos de Datos como Asunto , Redes Reguladoras de Genes/fisiología , Ratones , MicroARNs/metabolismo , ARN Mensajero/metabolismo
19.
Sci Total Environ ; 750: 143085, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33182181

RESUMEN

Microplastics (MPs) are ubiquitous contaminants in the environment and can be transferred along the food chain, thus causing adverse effects in organisms, even human beings. Therefore, it is of practical importance to identify the environmental risks of MPs, which could lead to a significant impact on public health. In addition to the healthy population, there are large numbers of patients with chronic diseases around the world whose responses to MPs are understudied, representing a significant knowledge gap within the health risk assessment of MPs. In this study, the response sensitivity to MPs of mice with acute colitis was compared with that of healthy mice. The mice were fed water containing polystyrene microplastics (PS MP) at a concentration of 500 µg/L for 28 days. The results showed that PS MP exposure induced inflammatory effects and exerted great disturbance on liver metabolites. Moreover, exposure to PS MP exaggerated dextran sodium sulfate (DSS)-induced acute colitis, as well as lipid disorders, as verified by typical inflammatory factor expression and triglyceride accumulation. The increased intestinal permeability of mice with acute colitis caused by exposure to PS MP may be responsible for the upregulated adverse effects. The results of this study suggest that populations with chronic diseases might be more sensitive to environmental contamination, which should be considered during health risk assessments.


Asunto(s)
Colitis , Contaminantes Químicos del Agua , Animales , Colitis/inducido químicamente , Humanos , Hígado , Ratones , Microplásticos , Plásticos , Poliestirenos , Contaminantes Químicos del Agua/toxicidad
20.
Food Chem ; 337: 127771, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32777564

RESUMEN

Faveleira (Cnidoscolus quercifolius) is an emerging Brazilian plant, with seeds rich in edible oil. This study investigates physicochemical properties, chemical composition, thermal and oxidative stability, in vitro and in vivo toxicity, antioxidant, antinociceptive and anti-inflammatory activities of faveleira seed oil. It was observed that the oil has low acidity, value of peroxide, chlorophyll, carotenoids, ß-carotene and high concentrations of unsaturated fatty acids. In addition to presenting thermal and oxidative stability and high total phenolic content, with vanillin, eugenol and quercetin were predominating. The oil showed no toxicity in vitro and in vivo, and presented antioxidant, anti-inflammatory and antinociceptive activities. These findings provide relevant and appropriate conditions for processing of faveleira seed oil as functional food.


Asunto(s)
Euphorbiaceae/metabolismo , Aceites Vegetales/química , Analgésicos/química , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Antioxidantes/química , Brasil , Carotenoides/análisis , Supervivencia Celular/efectos de los fármacos , Clorofila/análisis , Euphorbiaceae/química , Ácidos Grasos/análisis , Masculino , Ratones , Dolor/inducido químicamente , Dolor/prevención & control , Fenoles/análisis , Aceites Vegetales/farmacología , Aceites Vegetales/uso terapéutico , Células RAW 264.7 , Semillas/química , Semillas/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA