Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 98
Filtrar
1.
Cancer Manag Res ; 13: 8535-8550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803402

RESUMO

Purpose: The occurrence and development of lung adenocarcinoma (LUAD) are related to many factors. Multiple researches showed that the renin-angiotensin system (RAS) plays an important role in lung cancer. This research mainly focuses on angiotensin II receptor 1 (AT1R) encoding gene AGTR1, an important part of the RAS. Methods: We comprehensively evaluated the expression of AGTR1 in pan-cancer based on RNA sequencing data obtained from The Cancer Genome Atlas (TCGA). We explored the correlation of AGTR1 with clinicopathological features, prognosis and tumor microenvironment in LUAD. We also explored the mechanism through enrichment analysis and verified it with cell lines and tissue samples. Results: We found that AGTR1 was less expressed in most tumors and related to prognosis based on the TCGA database. To further explore its mechanism, we mainly focused on LUAD. Combined with the verification results in the GEO database, AGTR1 was associated with a better prognosis in LUAD. High expression of AGTR1 was associated with less lymph node metastasis (P=0.007) and MET mutation (P=0.019). High expression of AGTR1 was related to the anti-tumor immune microenvironment with high infiltration of B cells, myeloid dendritic cells, monocytes, and low infiltration of myeloid-derived suppressor cells (all P<0.05). Enrichment analysis and in vitro verification results showed that AGTR1 was likely to play a role in LUAD through the PI3K/AKT3 pathway. Finally, we verified the above results through tissue samples and the construction of AGTR1 overexpressing cells. Conclusion: AGTR1 inhibits the progression of lung adenocarcinoma through the PI3K/AKT3 pathway.

2.
Environ Pollut ; 290: 118079, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488161

RESUMO

The residue of polychlorinated biphenyls (PCBs) exists throughout the environment and humans are subject to long-term exposure. As such, the potential environmental and health risk caused by low-dose exposure to PCBs has attracted much attention. 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126), the highest toxicity compound among dioxin-like-PCBs, has been widely used and mass-produced. Cardiotoxicity is PCB126's crucial adverse effect. Maintaining proper metabolism underlies heart health, whereas the impact of PCB126 exposure on cardiac metabolic patterns has yet to be elucidated. In this study, we administered 0.5 and 50 µg/kg bw of PCB126 to adult male mice weekly by gavage for eight weeks. Pathological results showed that low-dose PCB126 exposure induced heart injury. Metabolomic analysis of the heart tissue exposed to low-dose PCB126 identified 59 differential metabolites that were involved in lipid metabolism, amino acid metabolism, and the tricarboxylic acid (TCA) cycle. Typical metabolomic characteristic of cardiac hypertrophy was reflected by accumulation of fatty acids (e.g. palmitic, palmitoleic, and linoleic acid), and disturbance of carbohydrates including D-glucose and intermediates in TCA cycle (fumaric, succinic, and citric acid). Low-dose PCB126 exposure increased glycine and threonine, the amino acids necessary for the productions of collagen and elastin. Besides, PCB126-exposed mice exhibited upregulation of collagen synthesis enzymes and extracellular matrix proteins, indicative of cardiac fibrosis. Moreover, the expression of genes related to TGFß/PPARγ/MMP-2 signaling pathway was perturbed in the PCB126-treated hearts. Together, our results reveal that low-dose PCB126 exposure disrupts cardiac metabolism correlated with hypertrophy and fibrosis. This study sheds light on the underlying mechanism of PCBs' cardiotoxicity and identifies potential sensitive biomarkers for environmental monitoring.


Assuntos
Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animais , Fibrose , Hipertrofia , Metabolismo dos Lipídeos , Masculino , Camundongos , Bifenilos Policlorados/toxicidade
3.
Fitoterapia ; 155: 104970, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34419561

RESUMO

The natural product Huperzine A isolated from Huperzia serrata is a targeted inhibitor of acetylcholinesterase that has been approved for clinical use in the treatment of Alzheimer's disease. Given the large demand for natural sources of Huperzine A  (Hup. A), efforts have been made to explore whether it is also produced by endophytic fungi from H. serrata and, if so, identify its biosynthetic pathway. These studies have indicated that endophytic fungi from H. serrata represent a huge and largely untapped resource for natural products (including Hup. A) with chemical structures that have been optimized by evolution for biological and ecological relevance. To date, more than three hundred endophytic fungi have been isolated from H. serrata, of which 9 strains can produce Hup. A, whilst more than 20 strains produce other important metabolites, such as polyketones, xanthones, alkaloids, steroids, triterpenoids, furanone derivatives, tremulane sesquitepenes and diterpenoids. In total, 200 secondary metabolites have been characterized in endophytic fungi from H. serrata to date. Functionally, some have cholinesterase-inhibitory or antibacterial activity. This review also considers the different classes of secondary metabolites produced by endophytic fungi, along with their possible applications. We systematically describe the taxonomy, biology, and chemistry of these secondary metabolites. It also summarizes the biosynthetic synthesis of metabolites, including that of Hup. A. The review will aid researchers in obtaining a clearer understanding of this plant-endophyte relationship to better exploit the excellent resources it offers that may be utilized by pharmaceutical industries.

4.
Plant Sci ; 308: 110909, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34034866

RESUMO

Adventitious root (AR) formation is of great significance for apple rootstock breeding. It is widely accepted that miR393 influences AR formation in many plant species; however, the molecular mechanism by which factors regulate AR formation remains insufficient. In this study, the evolutionary relationship of mdm-miR393 and candidate target genes MdTIR1/AFB was systematically identified, and the expression patterns were analysed. Multisequence alignment analysis of miR393 family members suggests that miR393 conservatively evolved between different species. The evolutionary relationship of the TIR1/AFBs can be divided into G1, G2 and G3 subgroups. During AR formation, the expression level of mdm-miR393a/b/c was significantly upregulated at 1 d and 7 d by exogenous auxin treatment. Furthermore, the expression levels of MdTIR1A, MdTIR1D, MdAFB1, MdAFB2, MdAFB3, MdAFB4 and MdAFB8 also appeared to be significantly changed by exogenous auxin induction. Subsequently, tissue-specific expression analysis showed that the expression levels of mdm-miR393 and MdTIR1/AFBs in different tissues exhibited significant differences. The promoter of mdm-miR393 contains multiple elements that respond to ABA, adversity and light signals; auxin treatment can activate the mdm-MIR393b promoter but is obviously inhibited by NPA treatment. The targeting relationship between mdm-MIR393b and MdTIR1A was verified by expression patterns, degradation group data, transient tobacco conversion results, and genes functions experiments. Heterologous overexpression of mdm-MIR393b (35S::mdm-MIR393b) decreased the number of ARs in the phenotype and reduced the expression level of the target gene NtTIR1 in tobacco. Compared to the wild type, the 35S::mdm-MIR393b transgenic plants demonstrated insensitivity to auxin. Furthermore, tir1 mutant exhibited reduced root system structure relative to the control. The above results illustrated that mdm-MIR393b is involved in mediating AR formation by targeted regulation of MdTIR1A expression in apple rootstock.


Assuntos
Proteínas F-Box/genética , Ácidos Indolacéticos/metabolismo , Malus/genética , MicroRNAs/genética , Proteínas de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , RNA de Plantas/genética , Sequência de Bases , Proteínas F-Box/metabolismo , Malus/crescimento & desenvolvimento , MicroRNAs/metabolismo , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , RNA de Plantas/metabolismo , Alinhamento de Sequência
5.
Eur J Pharmacol ; 896: 173923, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33539818

RESUMO

Chemotherapies such as 5-fluorouracil (5-FU) and cisplatin (CDDP) have been widely used to treat laryngeal squamous cell carcinoma (LSCC), the second most common head and neck squamous cell carcinoma. However, chemoresistance seriously impairs chemotherapeutic efficacy. Our present study reveals that 5-FU and CDDP treatment increase the expression of histone deacetylase 1 (HDAC1) in LSCC cells. Consistently, increased levels of HDAC1 are observed in chemoresistant cells. Knockdown of HDAC1 significantly restores the sensitivity of LSCC cells, as HDAC1 increases the expression of interleukin-8 (IL-8), which is essential for LSCC chemoresistance. Mechanistically, HDAC1 directly initiates the transcription of IL-8 though binding to its promoter. Simultaneously, si-HDAC1 increases the levels of miR-93, which binds to the 3'UTR of IL-8 mRNA to trigger its degradation. In summary, the HDAC1/IL-8 axis can confer chemotherapeutic resistance to LSCC cells.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Fluoruracila/farmacologia , Histona Desacetilase 1/metabolismo , Interleucina-8/metabolismo , Neoplasias Laríngeas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1/genética , Humanos , Interleucina-8/genética , Neoplasias Laríngeas/enzimologia , Neoplasias Laríngeas/patologia , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/enzimologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
6.
Exp Physiol ; 106(4): 958-971, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33517584

RESUMO

NEW FINDINGS: What is the central question of this study? The aim was to investigate whether diaphragm hypertrophy and gastrocnemius atrophy during hibernation of Daurian ground squirrels involve differential regulation of protein metabolism and regeneration. What is the main finding and its importance? We clarified the differences in protein metabolism and muscle regenerative potential in the diaphragm and gastrocnemius of hibernating ground squirrels, reflecting the different adaptability of muscles. ABSTRACT: Are differences in the regulation of protein metabolism and regeneration involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in cross-sectional area (CSA) and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1 and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1 and LC3-II) and muscle regeneration (MyoD, myogenin and myostatin). In the hibernation group compared with the summer active group, the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4%. Our study also indicated that increased protein synthesis, decreased protein degradation and increased muscle regenerative potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation and decreased muscle regenerative potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism might contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.

8.
Environ Pollut ; 268(Pt B): 115733, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011576

RESUMO

With numerous new chemicals introduced into the environment everyday, identification of their potential hazards to the environment and human health is a considerable challenge. Developing adverse outcome pathway (AOP) framework is promising in helping to achieve this goal as it can bring In Vitro testing into toxicity measurement and understanding. To explore the toxic mechanism underlying environmental chemicals via the AOP approach, an integration of adequate experimental data with systems biology understanding is preferred. Here, we describe a novel method to develop reliable and sensible AOPs that relies on chemical-gene interactions, toxicity pathways, molecular regulations, phenotypes, and outcomes information obtained from comparative toxicogenomics database (CTD) and Ingenuity Pathway Analysis (IPA). Using Benzo(a)pyrene (BaP), a highly studied chemical as a stressor, we identified the pivotal IPA toxicity pathways, the molecular initiating event (MIE), and candidate key events (KEs) to structure AOPs in the liver and lung, respectively. Further, we used the corresponding CTD information of multiple typical AHR-ligands, including 2,3,7,8-tetrachlorodibenzoparadioxin (TCDD), valproic acid, quercetin, and particulate matter, to validate our AOP networks. Our approach is likely to speed up AOP development as providing a time- and cost-efficient way to collect all fragmented bioinformation in published studies. It also facilitates a better understanding of the toxic mechanism of environmental chemicals, and potentially brings new insights into the screening of critical paths in the AOP network.


Assuntos
Rotas de Resultados Adversos , Bases de Dados Factuais , Humanos , Fígado , Fenótipo , Medição de Risco , Toxicogenética
9.
J Hazard Mater ; 404(Pt B): 124111, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189059

RESUMO

With the spread of organophosphorus flame retardants (OPFRs), the environmental and health risks they induce are attracting attention. Triphenyl phosphate (TPHP) is a popular alternative to brominated flame retardant and halogenated OPFRs. Neurodevelopmental toxicity is TPHP's primary adverse effect, whereas the biomarkers and the modes of action have yet to be elucidated. In the present study, 0.5, 5, and 50 mg/kg of TPHP were orally administered to mice from postnatal day 10 (P10) to P70. The behavioral tests showed a compromised learning and memory capability. Proteomic analysis of the hippocampus exposed to 0.5 or 50 mg/kg of TPHP identified 531 differentially expressed proteins that were mainly involved in axon guidance, synaptic function, neurotransmitter transport, exocytosis, and energy metabolism. Immunoblot and immunofluorescence analysis showed that exposure to TPHP reduced the protein levels of TUBB3 and SYP in the synapses of hippocampal neurons. TPHP exposure also downregulated the gene expression of neurotransmitter receptors including Grins, Htr1α, and Adra1α in a dose-dependent fashion. Moreover, the calcium-dependent synaptic exocytosis governed by synaptic vesicle proteins STX1A and SYT1 was inhibited in the TPHP-treated hippocampus. Our results reveal that TPHP exposure causes abnormal learning and memory behaviors by disturbing synaptogenesis and neurotransmission.


Assuntos
Retardadores de Chama , Animais , Retardadores de Chama/toxicidade , Hipocampo , Camundongos , Organofosfatos/toxicidade , Proteômica , Transmissão Sináptica , Sinaptotagmina I , Peixe-Zebra
10.
Virol J ; 17(1): 173, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176821

RESUMO

With CA16, enterovirus-71 is the causative agent of hand foot and mouth disease (HFMD) which occurs mostly in children under 5 years-old and responsible of several outbreaks since a decade. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death; EV71 has been identified in all severe cases. Therefore, it is actually one of the most public health issues that threatens children's life. [Formula: see text] is a protease which plays important functions in EV71 infection. To date, a lot of [Formula: see text] inhibitors have been tested but none of them has been approved yet. Therefore, a drug screening is still an utmost importance in order to treat and/or prevent EV71 infections. This work highlights the EV71 life cycle, [Formula: see text] functions and [Formula: see text] inhibitors recently screened. It permits to well understand all mechanisms about [Formula: see text] and consequently allow further development of drugs targeting [Formula: see text]. Thus, this review is helpful for screening of more new [Formula: see text] inhibitors or for designing analogues of well known [Formula: see text] inhibitors in order to improve its antiviral activity.


Assuntos
Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Enterovirus Humano A/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Doença de Mão, Pé e Boca/tratamento farmacológico , RNA Viral/antagonistas & inibidores , Animais , Antivirais/isolamento & purificação , Criança , Avaliação Pré-Clínica de Medicamentos/tendências , Enterovirus Humano A/enzimologia , Inibidores Enzimáticos/isolamento & purificação , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/virologia , Humanos , Camundongos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Filogenia
11.
J Diabetes Complications ; 34(10): 107666, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32636061

RESUMO

AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-fourCOVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P<0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4+T lymphocyte counts in severe patients were lower than those in non-severe patients (P<0.05). Logistic regression analysis identified decreased CD4+T lymphocyte counts (odds ratio [OR]=0.988, 95%Confidence interval [95%CI] 0.979-0.997) and increased SAA levels (OR=1.029, 95%CI 1.002-1.058) as risk factors for severity of COVID-19 with diabetes (P<0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4+T lymphocyte counts and high SAA levels.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , COVID-19 , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Taxa de Sobrevida , Avaliação de Sintomas
12.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204528

RESUMO

Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a significant cause of morbidity and mortality worldwide, in people of all ages. A series of novel 2-benzoxyl-phenylpyridine derivatives were evaluated for their potential antiviral activities against CVB3 and adenovirus type 7 (ADV7). Preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on both CVB3 and ADV7 viruses; they could effectively inhibit virus-induced cytopathic effects, reduce viral progeny yields, and had similar or superior antiviral activities compared with the control drug, ribavirin. Further, these compounds targeted the early stages of CVB3 replication in cells, including viral RNA replication and protein synthesis, rather than inactivating the virus directly, inhibiting virus adsorption/entry, or affecting viral release from cells. Our data demonstrate that the tested 2-benzoxyl-phenylpyridine derivatives are effective inhibitors of CVB3 and ADV7, raising the possibility that these compounds might be feasible candidates for anti-viral agents.


Assuntos
Antivirais/síntese química , Enterovirus Humano B/fisiologia , Piridinas/síntese química , Adenovírus Humanos/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Células HeLa , Humanos , Estrutura Molecular , Piridinas/química , Piridinas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
13.
Arch Toxicol ; 94(2): 541-552, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894355

RESUMO

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a phosphorus-based flame retardant common in consumer goods and baby products. Concerns have been raised about TDCPP exposure and neurodevelopmental toxicity. However, the mechanism and early response for TDCPP-induced neurotoxicity are poorly understood. This study investigates the role of microglia-mediated neuroinflammation in TDCPP-induced neurotoxicity in mice and primary cells. TDCPP was administered to C57BL/6 pups (0, 5, or 50 mg/kg/day) via an oral gavage from postnatal days 10-38 (28 days). The results showed that TDCPP exposure for 28 days altered the gene expression of neuronal markers Tubb3, Nefh, and Nes, and led to apoptosis in the hippocampus. The mRNA levels of pro-inflammatory factors Il-1ß, Tnfα and Ccl2 dose dependently increased in the hippocampus at both 24 h and 28 days following exposure, accompanied by microglia activation characterized by an amoeboid-like phenotype. In in vitro studies using the primary microglia isolated from neonatal mice, exposure to TDCPP (0-100 µM) for 24 h resulted in cellular activation. It also increased the expression of genes responsible for inflammatory responses including surface markers and pro-inflammatory cytokines. These changes occurred in a dose-dependent fashion. Neurite outgrowth of primary mouse hippocampal neurons was inhibited by treatment with the conditioned medium harvested from microglia exposed to TDCPP. These results reveal that neonatal exposure to TDCPP induces neuronal damage through microglia-mediated inflammation. This provides insight into the mechanism of TDCPP's neurodevelopmental toxicity, and suggests that microglial cell is a sensitive responder for OPFRs exposure.


Assuntos
Retardadores de Chama/toxicidade , Hipocampo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Síndromes Neurotóxicas/patologia , Compostos Organofosforados/toxicidade , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiologia , Inflamação/induzido quimicamente , Masculino , Camundongos Endogâmicos C57BL , Microglia/patologia , Síndromes Neurotóxicas/etiologia , Testes de Toxicidade/métodos
14.
Front Physiol ; 10: 1449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824343

RESUMO

Hibernating mammals experience conditions of extreme oxidative stress, such as fasting, muscle disuse, and repeated hypoxic ischemia-reperfusion, during the torpor-arousal cycle. Despite this, they experience little oxidative injury and are thus an interesting model of anti-oxidative damage. Thus, in the current study, we explored the levels and underlying mechanism of oxidative stress and antioxidant capacity in three skeletal muscles [slow-twitch soleus (SOL), fast-twitch extensor digitorum longus (EDL), and mixed gastrocnemius (GAS)] of Daurian ground squirrels (Spermophilus dauricus) during hibernation. Results showed that hydrogen peroxide content in the EDL and GAS decreased significantly during pre-hibernation (PRE) and late torpor (LT) compared to levels in the summer active (SA) group. Furthermore, relative to SA levels, malondialdehyde content decreased significantly during interbout arousal (IBA) and early torpor (ET) in all three skeletal muscles and decreased in the EDL and GAS during LT. Compared with the SA group, glutathione peroxidase 1 (GPx1) and catalase (CAT) protein expression in the SOL and superoxide dismutase 1 (SOD1) and SOD2 expression in the GAS increased significantly during the entire hibernation season. Furthermore, SOD1 in the IBA group and CAT and GPx1 in the ET and LT groups increased significantly in the EDL. The activities of most tested antioxidant enzymes were higher in the IBA group than in the LT group, whereas CAT remained highly active throughout the hibernation season in all three muscles. Nrf2 and p-Nrf2 protein levels were significantly elevated in the SOL and EDL during hibernation, and increased during the PRE, IBA, and ET states in the GAS. Thus, activation of the Nrf2/Keap1 antioxidant pathway resulted in the elimination of excess reactive oxygen species (ROS). Specifically, ROS levels were maintained at physiological levels by the up-regulation of antioxidant enzyme expression in skeletal muscles under oxidative stress during hibernation, thus preventing oxidative injury over the torpor-arousal cycle. Different antioxidant patterns and oxidative stress levels were also observed among the different skeletal muscles of hibernating Daurian ground squirrels.

15.
BMC Neurosci ; 20(1): 36, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366324

RESUMO

BACKGROUND: Postoperative pain (POP) is a severe acute pain encountered in patients suffering from an operation, and is less than adequately controlled by the currently available analgesics. Phosphatidylinositol 3-kinase (PI3K) has been reported to have an important role in neuropathic and inflammatory pain. Our previous research revealed that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice. The aim of this study was to clarify whether post-surgical inhibition of PI3K would attenuate the POP and the underlying mechanisms. METHODS: A POP model was established by plantar incision in Kunming mice. A behavioral test was performed to determine mechanical allodynia, thermal hyperalgesia, and cumulative pain scores. The spinal Fos was detected by immunohistochemistry. The spinal expression of protein kinase B (Akt) or phosphorylated Akt (pAkt) was explored using western blot. The cellular location of pAkt was determined by immunofluorescence. RESULTS: Post-surgical inhibition of PI3K attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision significantly in male mice, and mildly in female mice. Post-surgical inhibition of PI3K attenuated the expression of spinal Fos in male mice. Plantar incision induced a time-dependent expression of spinal pAkt in male mice, which was primarily expressed in the spinal dorsal horn, and localized with the neuron and microglia's marker. Post-surgical inhibition of PI3K attenuated the activation of Akt induced by plantar incision in male mice as well. CONCLUSIONS: We concluded that post-surgical inhibition of PI3K could attenuate the pain-related behaviors induced by plantar incision, by suppressing the activation of spinal Akt in male mice. This finding might be used in clinical studies to reach a better understanding of POP mechanisms and optimal treatment.


Assuntos
Cromonas/farmacologia , Hiperalgesia/fisiopatologia , Morfolinas/farmacologia , Dor Pós-Operatória/prevenção & controle , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Wortmanina/farmacologia , Animais , Feminino , Traumatismos do Pé/complicações , Hiperalgesia/complicações , Hiperalgesia/prevenção & controle , Masculino , Camundongos , Medição da Dor/efeitos dos fármacos , Dor Pós-Operatória/complicações , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Caracteres Sexuais , Medula Espinal/metabolismo
16.
Aquat Toxicol ; 214: 105224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31255847

RESUMO

Polybrominated diphenyl ethers (PBDEs) are distributed throughout the environment. Despite a moratorium on their use, concentrations of PBDEs in the atmosphere and in residential environments remain high due to their persistence. The environmental health risks remain concerning and one of the major adverse effects is neurodevelopmental toxicity. However, the early response and effects of PBDEs exposure on the developing brain remain unknown. In the present study, we investigated the impacts of 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) on vascular growth and vascular barrier function with an emphasis on cerebral blood vessels, in the early life stages, using a zebrafish model. No general toxicity was observed in exposing zebrafish larvae to 0-0.5 µM BDE-99 at 72 hpf. BDE-99 exposure resulted in neither general toxicity nor pronounced developmental impairment in somatic blood vessels, including intersegmental vessels (ISV) and common cardinal veins (CCV). Meanwhile, both 0.05 µM and 0.5 µM of BDE-99 reduced cerebrovascular density as well as down-regulation of VEGFA and VEGFR2 in the head. In addition, BDE-99 exposure increased vascular leakage, both in cerebral and truncal vasculature at 72 hpf. The accentuated vascular permeability was observed in the head. The mRNA levels of genes encoding tight junction molecules decreased in the BDE-99-exposed larvae, and more robust reductions in Cldn5, Zo1 and Jam were detected in the head than in the trunk. Moreover, proinflammatory factors including TNF-α, IL-1ß and ICAM-1 were induced, and the expression of neurodevelopment-related genes was suppressed in the head following BDE-99 exposure. Taken together, these results reveal that developmental exposure to BDE-99 impedes cerebrovascular growth and disturbs vascular barrier formation. The cerebral vasculature in developing zebrafish, a more sensitive target for BDE-99, may be a promising tool for the assessment of the early neurodevelopmental effects due to PBDEs exposure.


Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Exposição Ambiental , Éteres Difenil Halogenados/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Animais , Encéfalo/irrigação sanguínea , Encéfalo/crescimento & desenvolvimento , Permeabilidade Capilar/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Larva/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
17.
Chemosphere ; 227: 647-656, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31015085

RESUMO

In this study, CuFe2O4 nanocomposite loaded on natural sepiolite (CuFe2O4/SEP) was prepared by the citrate sol-gel method. CuFe2O4/SEP was characterized by X-ray diffraction, Brunauer-Emmett-Teller adsorption analysis, scanning electron microscopy, and energy dispersive spectroscopy. The CuFe2O4/SEP composite was stable and showed an excellent catalytic activity for ozonation. The efficiency of quinoline mineralization in the catalytic ozonation with CuFe2O4/SEP was 90.3%, and this value was 5.4 times higher than that of the uncatalyzed ozonation (16.8%). The quinoline mineralization followed a pseudo first-order kinetics with all the catalysts. The rate constant for the mineralization of quinoline by ozonation in the presence of CuFe2O4/SEP was 0.0885 min-1, which was 16.7 times higher than that in ozone alone (0.0053 min-1). Radical scavenging tests revealed that hydroxyl radical (OH) and superoxide radical (O2-) were the reactive oxygen species (ROS) in the quinoline degradation. In the presence of CuFe2O4/SEP, ozone and hydrogen peroxide were rapidly converted into the ROS. Although neutral and alkaline pH were more beneficial for the quinoline mineralization, CuFe2O4/SEP exhibited significant catalytic activity even under acidic conditions. Meanwhile, five-cycle successive tests suggested that CuFe2O4/SEP was recyclable and hence, stable. Furthermore, the feasibility of the catalytic ozonation for the treatment of biologically treated coking wastewater was evaluated. The catalytic ozonation resulted in 57.81% total organic carbon removal efficiency at 60 min, which was 2.9 times higher than that in the uncatalyzed ozonation (19.99%).


Assuntos
Coque/análise , Cobre/química , Compostos Ferrosos/química , Ozônio/química , Quinolinas/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Catálise , Silicatos de Magnésio/química
18.
J Cell Physiol ; 234(11): 19728-19739, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30941772

RESUMO

Stress conditions like hypoxia, ischemia, and ischemia/reperfusion can trigger excessive endoplasmic reticulum stress (ERS), which can lead to cell apoptosis-induced skeletal muscle atrophy in non-hibernators. However, although hibernators experience multiple stress conditions during hibernation, their skeletal muscles appear to be well protected. We hypothesize that hibernators effectively avoid cell apoptosis, at least partially, by controlling ERS level. Here, we focused on the potential occurrence of ERS and how hibernators cope with it during different hibernation states. Results indicated that the protein expression levels of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like ER protein kinase, phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), and activating transcription factor 4 were significantly increased during hibernation, but primarily recovered in posthibernation. In the torpor-arousal cycle, the expression levels of the above indicators were lower during inter-bout arousal (IBA) than that during late torpor (LT). However, there was no change in C/EBP homologous protein expression and no apoptosis in skeletal muscles during the different hibernation states. In conclusion, the upregulation of p-eIF2α and GRP78 were identified as two crucial mechanisms mediated by the PERK signaling pathway to alleviate elevated ERS. The downregulation of ERS during IBA may be a unique countermeasure for hibernating squirrels to prevent excessive ERS. Thus, these special anti-excessive ERS abilities of ground squirrels contribute to the prevention of skeletal muscle cell apoptosis during hibernation.


Assuntos
Hibernação/genética , Atrofia Muscular/genética , Sciuridae/fisiologia , eIF-2 Quinase/genética , Animais , Apoptose/genética , Estresse do Retículo Endoplasmático/genética , Fator de Iniciação 2 em Eucariotos/genética , Regulação da Expressão Gênica/genética , Proteínas de Choque Térmico/genética , Hibernação/fisiologia , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Sciuridae/genética , Transdução de Sinais/genética , Fator de Transcrição CHOP
19.
Plant Physiol Biochem ; 139: 66-81, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878839

RESUMO

Adventitious root (AR) formation is essential for the vegetative propagation of apple rootstocks. miRNAs play a significant role in regulating AR development, however, large-scale transcriptomic data on miRNA mediated AR formation in apple rootstocks is lacking. Therefore, in order to identify the molecular mechanisms underlying AR formation in 'M9-T337' apple rootstocks, transcriptomic changes occurring during key time points of AR formation (0, 3, and 16 days) were analyzed using high-throughput sequencing with a focus on miRNAs. A total of 84 known miRNAs and 56 novel miRNAs have differentially expressed were identified. Additionally, a total of 88 target genes of known miRNAs and 76 target genes of novel miRNAs were identified by degradome sequencing. The expression levels of the miRNAs and target genes were quantified by RT-qPCR. Results indicate that miRNAs and their target genes are associated with auxin signal-related (miR160 and miR390), stress response-related (miR398, miR395 and miR408), cell fate transformation-, proliferation- and enlargement-related (miR171, miR156, miR166, miR319 and miR396). These all involve pathways that participate in AR formation in 'M9-T337' apple rootstock. In addition, hormones (AUX, CTK, GA3, BR, JA, and ABA) are also involved in regulating AR formation. The candidate genes belonging to pathways associated with AR formation exhibited significantly higher expression levels, providing evidence that they may be involved in the regulation of AR development. The collective results of the present study indicate that the developmental process associated with AR formation in apple rootstock is extremely complex. The known and novel miRNAs and target genes that were identified by high-throughput and degradome sequencing, respectively, provide a framework for the future analysis of miRNAs associated with AR development in apple rootstocks, and provide new information that can be used to better understand AR development in woody plants.


Assuntos
Ácidos Indolacéticos/metabolismo , Malus/crescimento & desenvolvimento , MicroRNAs/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Transdução de Sinais , Regulação da Expressão Gênica de Plantas , Malus/metabolismo , Malus/fisiologia , MicroRNAs/fisiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/fisiologia , Reação em Cadeia da Polimerase , Estresse Fisiológico
20.
J Inorg Biochem ; 193: 130-132, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711559

RESUMO

A new strategy to construct polyoxovanadate hybrids incorporating amino acid esters in mild conditions was presented in this paper. These new hybrids were not only structurally determined by Single Crystal X-Ray diffraction, but also exhibited higher antitumor activities against laryngeal carcinoma, rhabdomyoma, and breast adenocarcinoma tumor cells compared with the traditional commercial medicine 5-fluorouracil. These results would provide a promising lead scaffold for further design and synthesis of potential anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Vanadatos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/farmacologia , Humanos , Vanadatos/síntese química , Vanadatos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...