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1.
Toxicology ; 431: 152353, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887333

RESUMO

Exposure to environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes cleft palate at high rates, but little is known about the underlying biological mechanisms. In the present study, we cultured osteoblasts from human fetal palate mesenchymal cells (hFPMCs) to explore the effects of TCDD on osteogenic differentiation. The results showed that TCDD significantly decreased cell proliferation, alkaline phosphatase (ALP) activity and calcium deposition. RNA analyses and protein detection demonstrated that TCDD downregulated a wide array of pro-osteogenic biomarkers. Further investigation of the underlying molecular mechanisms revealed that exposure to TCDD activated aryl hydrocarbon receptor (AhR) signaling and inhibited BMP-2/TGF-ß1/Smad pathway molecules. The inactivation of AhR signaling using CRISPR/Cas9-mediated AhR deletion or by genetic siRNA knockdown significantly blocked the effects induced by TCDD, suggesting a critical role of AhR activation in the TCDD-mediated inhibition of hFPMC osteogenic differentiation. The cotreatment with TGF-ß1 or BMP-2 and TCDD significantly relieved the activation of AhR and rescued the impairment of osteogenesis caused by TCDD. Taken together, our findings indicated that TCDD inhibited the osteogenic differentiation of hFPMCs via crosstalk between AhR and BMP-2/TGF-ß1/Smad signaling pathway.

2.
Nat Commun ; 10(1): 4827, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645592

RESUMO

Macroautophagy, a key player in protein quality control, is proposed to be systematically impaired in distinct tissues and causes coordinated disruption of protein homeostasis and ageing throughout the body. Although tissue-specific changes in autophagy and ageing have been extensively explored, the mechanism underlying the inter-tissue regulation of autophagy with ageing is poorly understood. Here, we show that a secreted microRNA, mir-83/miR-29, controls the age-related decrease in macroautophagy across tissues in Caenorhabditis elegans. Upregulated in the intestine by hsf-1/HSF1 with age, mir-83 is transported across tissues potentially via extracellular vesicles and disrupts macroautophagy by suppressing CUP-5/MCOLN, a vital autophagy regulator, autonomously in the intestine as well as non-autonomously in body wall muscle. Mutating mir-83 thereby enhances macroautophagy in different tissues, promoting protein homeostasis and longevity. These findings thus identify a microRNA-based mechanism to coordinate the decreasing macroautophagy in various tissues with age.


Assuntos
Envelhecimento/genética , Caenorhabditis elegans/genética , MicroRNAs/genética , Animais , Autofagia/genética , Proteínas de Caenorhabditis elegans/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/metabolismo , Intestinos , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Músculos/metabolismo , Fatores de Transcrição/metabolismo
3.
EMBO Rep ; 20(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30872315

RESUMO

Dietary restriction (DR) is known to have a potent and conserved longevity effect, yet its underlying molecular mechanisms remain elusive. DR modulates signaling pathways in response to nutrient status, a process that also regulates animal development. Here, we show that the suppression of Wnt signaling, a key pathway controlling development, is required for DR-induced longevity in Caenorhabditis elegans We find that DR induces the expression of mir-235, which inhibits cwn-1/WNT4 expression by binding to the 3'-UTR The "switch-on" of mir-235 by DR occurs at the onset of adulthood, thereby minimizing potential disruptions in development. Our results therefore implicate that DR controls the adult lifespan by using a temporal microRNA switch to modulate Wnt signaling.

4.
J Drug Target ; 27(8): 866-875, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30601069

RESUMO

Recently, a wealth of information has emerged connecting the activation of the NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome to stroke pathogenesis, although the exact influence of the NLRP3 inflammasome on stroke is still in the stage of preliminary study and is awaiting further confirmation. In this paper, we will review the structure, assembly and activation of the NLRP3 inflammasome and its expression in the neurovascular units and will speculate on its possible roles in neurovascular injury post-stroke. Evidence on this topic suggests that targeting NLRP3-mediated inflammation at multiple levels may provide a new therapeutic strategy to prevent the deterioration of neurovascular units after stroke. However, many aspects of the biological link between the NLRP3 inflammasome and stroke remain ill-defined or even completely unknown. As fresh insights come to light regarding the NLRP3 inflammasome, the opportunities to develop new therapeutic strategies for stroke patients are expected to improve accordingly.

5.
Medicine (Baltimore) ; 97(50): e13476, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558002

RESUMO

RATIONALE: Multifocal cerebral hemorrhage refers to the cerebral hemorrhage in 2 or more lesions at the same time or 48 h in the brain caused by various causes, which has an acute onset, high mortality rate, and poor clinical treatment effect. Subarachnoid hemorrhage (SAH) is caused by the direct flow of blood into the subarachnoid cavity due to the rupture of the diseased vessels at the base or surface of the brain. Cerebral venous sinus thrombosis (CVST) affects approximately 5 people per million and accounts for approximately 1% of all stroke events. CVST with both SAH and multifocal intracerebral hemorrhage (ICH) as the first presentation is extremely rare. PATIENT CONCERNS: A 57-year-old woman presented with dizziness, nausea, and vomiting. DIAGNOSIS: Neuroimaging confirmed a diagnosis of CVST. INTERVENTIONS: The patient was treated with dehydration, scavenging free radicals, and nerve protection therapy. OUTCOMES: After 4 weeks of systematic treatment, the patient resumed independent daily activities and was discharged with only slight non-fluent aphasia. She did not exhibit recurrent thrombosis at an 18-month follow-up point. MAIN LESSONS: The usual treatment for sinus thrombosis is anticoagulation or local thrombolysis. Systemic anticoagulation is the first-line treatment for CVST, even in patients with cerebral hemorrhage or SAH. The present patient's hemorrhage clearly contraindicated heparin; therefore, no anticoagulants or thrombolytic agents were administered during the 4-week hospitalization. We discuss issues for consideration in similar cases and provide an example of determining an individualized approach to treatment.


Assuntos
Hemorragia Cerebral/etiologia , Trombose dos Seios Intracranianos/complicações , Hemorragia Subaracnóidea/etiologia , Feminino , Humanos , Pessoa de Meia-Idade
6.
Environ Sci Pollut Res Int ; 25(26): 26209-26217, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29974445

RESUMO

Antibiotic resistance genes (ARGs) are regarded as emerging contaminants related with human activities. Aquatic environments of an urban city are apt for the persistence and prevalence of ARGs. In this study, we investigated the occurrence and distribution of ARGs and integrase genes in the sediment samples collected from drinking water sources, urban rivers, and coastal areas of Zhuhai, China, in the dry and wet seasons of 2016. The results show that sulfonamide resistance gene of sulII was present at the highest detection frequency (85.71%); and its average concentrations were also the highest in both dry and wet seasons (3.78 × 107 and 9.04 × 107 copies/g sediment, respectively), followed by tetC, tetO, tetA, ermB, dfrA1, and blaPSE-1. Temporally, the concentrations of total ARGs in the wet season were likely higher than those in the dry season; and spatially, the concentrations of total ARGs in the drinking water sources were substantially lower than those in the urban rivers and nearby coastal areas, indicating the different degrees of anthropogenic impact and consequent health risks. Positive correlations were found between intI1 and each quantitative ARG in all wet season samples rather than dry season samples, which suggested higher temperature and more rain in summer might have positive influences on ARG dissemination, especially that mediated by intI1 gene and class I integrons.


Assuntos
Resistência Microbiana a Medicamentos/genética , Poluentes Ambientais/análise , Genes Bacterianos , Sedimentos Geológicos/análise , Antibacterianos , China , Cidades , Água Potável/análise , Humanos , Integrons , Reação em Cadeia da Polimerase , Rios/química , Estações do Ano , Sulfonamidas
7.
Sci Total Environ ; 636: 1009-1019, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29913564

RESUMO

The occurrence, spatiotemporal distribution and ecological risks of 27 antibiotics in water and sediments from rivers and coastal area of Zhuhai, Pearl River estuary, south China were investigated. Higher concentrations of antibiotics were found in river water in dry season than those in wet season (p < 0.01), especially for quinolones (QNs) (6.36-463 ng/L) and aminoglycosides (AGs) (94.9-458 ng/L). In coastal water samples, the concentrations of antibiotics were up to 419 ng/L and 357 ng/L in dry season and wet season, respectively. Higher concentrations of antibiotics in coastal sediment samples were observed in wet season compared with those in dry season (p < 0.01). This may be ascribed to the greater discharge of antibiotics from mariculture and surface sediment flushing in wet season, leading to the accumulation of polluted sediments in the estuary. Redundancy analysis showed that the concentrations of antibiotics in water were correlated with biological/chemical oxygen demand, ammonia nitrogen, and/or total nitrogen (TN). In addition, sediment organic matter (SOC) and TN strongly affected the distribution of antibiotics in sediments. Ecological risk assessment based on risk quotients (RQs) indicated that most antibiotics in water samples posed insignificant risk to fish and green algae, and insignificant to medium risk to daphnid.


Assuntos
Antibacterianos/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , China , Estuários , Sedimentos Geológicos/química , Rios/química
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