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1.
Angew Chem Int Ed Engl ; : e202410982, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935427

RESUMO

High-performance and temperature-resistant lithium-ion batteries (LIBs), which are able to operate at elevated temperatures (i.e., >60 °C) are highly demanded in various fields, especially in military or aerospace exploration. However, their applications were  impeded by the poor electrochemical performance and unsatisfying safety issues, which was induced by the severe side reactions between electrolytes and electrodes at high temperatures. Herein, with the synergetic effects of solvation chemistry and functional additive in the elaborately designed weakly solvating electrolyte, a unique robust organic/inorganic hetero-interphase, composed of gradient F, B-rich inorganic components and homogeneously distributed Si-rich organic components, was successfully constructed on both cathodes and anodes, which would effectively inhibit the constant decomposition of electrolytes and dissolution of transition metal ions. As a result, both cathodes and anodes, without compromising their low-temperature performance, operate at temperatures ≥100 ℃, with excellent capacity retentions of 96.1 % after 500 cycles and 93.5% after ≥200 cycles, respectively, at 80 ℃. Ah-level LiCoO2||graphite full cells with a cut-off voltage of 4.3 V also exhibited superior temperature-resistance with a capacity retention of 89.9% at temperature as high as 120 ℃. Moreover, the fully charged pouch cells exhibited highly enhanced safety, demonstrating their potentials in practical applications at ultrahigh temperatures.

2.
Biophys J ; 114(4): 929-938, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29490252

RESUMO

Regulation of cell volume is a fundamental property of all mammalian cells. Multiple signaling pathways are known to be activated by cell swelling and to contribute to cell volume homeostasis. Although cell mechanics and membrane tension have been proposed to couple cell swelling to signaling pathways, the impact of swelling on cellular biomechanics and membrane tension have yet to be fully elucidated. In this study, we use atomic force microscopy under isotonic and hypotonic conditions to measure mechanical properties of endothelial membranes including membrane stiffness, which reflects the stiffness of the submembrane cytoskeleton complex, and the force required for membrane tether formation, reflecting membrane tension and membrane-cytoskeleton attachment. We find that hypotonic swelling results in significant stiffening of the endothelial membrane without a change in membrane tension/membrane-cytoskeleton attachment. Furthermore, depolymerization of F-actin, which, as expected, results in a dramatic decrease in the cellular elastic modulus of both the membrane and the deeper cytoskeleton, indicating a collapse of the cytoskeleton scaffold, does not abrogate swelling-induced stiffening of the membrane. Instead, this swelling-induced stiffening of the membrane is enhanced. We propose that the membrane stiffening should be attributed to an increase in hydrostatic pressure that results from an influx of solutes and water into the cells. Most importantly, our results suggest that increased hydrostatic pressure, rather than changes in membrane tension, could be responsible for activating volume-sensitive mechanisms in hypotonically swollen cells.


Assuntos
Citoesqueleto de Actina/metabolismo , Aorta/metabolismo , Membrana Celular/química , Módulo de Elasticidade , Endotélio Vascular/metabolismo , Soluções Hipotônicas/farmacologia , Estresse Mecânico , Actinas/metabolismo , Aorta/citologia , Aorta/efeitos dos fármacos , Tamanho Celular , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Concentração Osmolar
3.
BMC Microbiol ; 18(1): 52, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866030

RESUMO

BACKGROUND: Iron plays important roles in the growth, reproduction and pathogenicity of Aeromonas hydrophila. In this study, we detected and compared the mRNA and protein expression profiles of A. hydrophila under normal and iron restricted medium with 200 µM 2,2-Dipyridyl using RNA Sequencing (RNA-seq) and isobaric tags for relative and absolute quantification (iTRAQ) analyses. RESULTS: There were 1204 genes (601 up- and 603 down-regulated) and 236 proteins (90 up- and 146 down-regulated) shown to be differentially expressed, and 167 genes and proteins that showed consistent expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially expressed genes and proteins were mainly involved in iron ion transport, protein activity, energy metabolism and virulence processes. Further validation of the RNA-seq and iTRAQ results by quantitative real-time PCR (qPCR) revealed that 18 of the 20 selected genes were consistently expressed. The iron-ion absorption and concentration of A. hydrophila under iron-limited conditions were enhanced, and most virulence factors (protease activity, hemolytic activity, lipase activity, and swimming ability) were also increased. Artificial A. hydrophila infection caused higher mortality in cyprinid Megalobrama amblycephala under iron-limited conditions. CONCLUSION: Understanding the responses of pathogenic Aeromonas hydrophila within the hostile environment of the fish host, devoid of free iron, is important to reveal bacterial infection and pathogenesis. This study further confirmed the previous finding that iron-limitation efficiently enhanced the virulence of A. hydrophila using multi-omics analyses. We identified differentially expressed genes and proteins, related to enterobactin synthesis and virulence establishment, that play important roles in addressing iron scarcity.


Assuntos
Aeromonas hydrophila/patogenicidade , Perfilação da Expressão Gênica/métodos , Proteômica/métodos , Regulação para Cima , Fatores de Virulência/genética , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Animais , Proteínas de Bactérias/genética , Cyprinidae/microbiologia , Metabolismo Energético , Regulação Bacteriana da Expressão Gênica , Ferro/metabolismo , Análise de Sequência de RNA
4.
Fish Physiol Biochem ; 43(4): 987-997, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28236008

RESUMO

Transferrin (Tf) plays an important function in iron homeostasis and metabolism of organisms. In this study, we identified and characterized the Tf gene in Megalobrama amblycephala and evaluated its expression in basal conditions as well as after iron overload and experimental infection with Aeromonas hydrophila. Furthermore, we studied the iron binding properties of recombinant Tf. The full-length M. amblycephala Tf complementary DNA (cDNA) (GenBank accession no.: KX698308) of 2245 bp was cloned and contained a 1953 bp open reading frame (ORF) encoding 650 amino acid residues and flanked by a 68 bp 5' and a 204 bp 3' untranslated regions (UTR). Predicted conservative structure illustrated that M. amblycephala Tf consisted of two conservative Tf domains. Amino acid sequence alignment revealed that M. amblycephala Tf had high similarity with that of cyprinids deposited in Genbank, and phylogenetic analysis showed that M. amblycephala Tf clustered with Ctenopharyngodon idella and Hypophthalmichthys molitrix. Tissue expression pattern analyses demonstrated that the liver was the main Tf mRNA expressing organ, being significantly higher than other tissues (p < 0.05). In the liver, Tf mRNA expression in fish artificially injected with the pathogenic bacteria A. hydrophila was significantly upregulated, reaching a peak at 12 h post injection (hpi) and then decreasing afterward. The expression in FeCl3-injected fish showed a similar tendency, but reached a peak at 8 hpi. Meanwhile, fish serum iron significantly decreased following A. hydrophila injection, but increased to peak at 4 hpi and then decreased in FeCl3-injected fish. The recombinant M. amblycephala Tf showed iron binding capacity using CAS analysis. These results are helpful to understand the structure and regulation of expression of Tf, as well as the specific function of Tf for both immune responses and iron homeostasis.


Assuntos
Aeromonas hydrophila , Clonagem Molecular , Regulação da Expressão Gênica/fisiologia , Ferro/farmacologia , Perciformes/metabolismo , Transferrina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Doenças dos Peixes/metabolismo , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Transferrina/genética
5.
Syst Parasitol ; 94(1): 73-80, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28062987

RESUMO

Actinosporean infection of oligochaetes living in the mud of a commercial gibel carp pond with myxosporean disease was studied. Six actinospore types were detected exclusively from the oligochaete Branchiura sowerbyi Beddard with very high prevalence (18%). Five out of the six types were identified as the same actinosporeans described in previous reports, the sixth actinosporean was identified as a new Neoactinomyxum type and described here based on morphological and molecular characterisation. Spore body of the actinospore was globular, much smaller than caudal processes. Three caudal processes were disc-like in apical view, hemispherical in side view, closer together and encircling the spore body. The number of sporoplasm cells was detected as eight in one specimen. The new actinosporean markedly differed from other Neoactinomyxum types in literature having much bigger caudal processes. DNA sequence analyses further confirmed the morphological identification, and revealed the actinosporean described here (KU641392) possessed less than 94% sequence similarity with myxozoans available in the GenBank database.


Assuntos
Myxozoa/classificação , Oligoquetos/parasitologia , Animais , Myxozoa/citologia , Myxozoa/genética , RNA Ribossômico 18S/genética , Especificidade da Espécie , Esporos de Protozoários/citologia
6.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(9): 1046-1050, 2016 Sep.
Artigo em Zh | MEDLINE | ID: mdl-30645840

RESUMO

Objective To observe the effect of Chinese herbs combined dehydroepiandrosterone (DHEA) pretreatment on pregnancy outcomes of elderly patients with normal ovarian function undergoing in vitro fertilization-embryo transfer ( IVF-ET). Methods Totally 233 IVF patients with normal ovarian function scheduled for IVF-ET, 36 -42 years old, were assigned to the combined group, the DHEA group, the control group according to random number table. Patients in the combined group (76 cases) were pretreated with Chinese herbs plus DHEA before IVF cycle for 8 weeks. Patients in the DHEA group (82 cases) were pretreated with DHEA before IVF cycle for 8 weeks. Those in the control group (75 cases) received no pretreatment. The number of retrieved oocytes , the fertilization rate, the rate of good quality embryos, the number of frozen embryos, clinical pregnancy rate, early spontaneous abortion rate, live birth rate, levels of anti-Mullerian hormone (AMH) , the cycle cancellation rate, endometrial thickness and estradiol (E2) level on human chorionic gonadotropin (hCG) injection day, the dosage and duration of Gn were observed in the 3 groups. Results The good quality embryo rate was significantly higher in the combined group and the DHEA group than in the control group (P <0. 05). Compared with the control group, the fertilization rate, the number of frozen embryos, the clinical pregnancy rate, and the live birth rate were higher; the early spontaneous abortion rate was lower in the two pretreatment groups (P > 0. 05). AMH increased more significantly in the two pretreatment groups after treatment (P <0. 05). There was no obvious change in the control group. The post-treatment number of retrieved oocytes, the cycle cancellation rate, E2 level and endometrial thickness on hCG injection day, the dosage and duration of Gn had no significant difference among the 3 groups (P >0. 05). Conclusion Pretreatment of Chinese herbs combined DHEA could improve the good quality embryo rate of elderly patients with normal ovarian re- serve, which might be associated with AMH.


Assuntos
Desidroepiandrosterona , Medicamentos de Ervas Chinesas , Fertilização in vitro , Reserva Ovariana , Aborto Espontâneo , Adulto , Idoso , Desidroepiandrosterona/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Transferência Embrionária , Feminino , Humanos , Indução da Ovulação , Gravidez , Resultado da Gravidez , Taxa de Gravidez
7.
Front Med (Lausanne) ; 11: 1344702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695028

RESUMO

Background and objective: It remains uncertain if the addition of Saccharomyces boulardii (S. boulardii) to bismuth quadruple therapy (BQT) recommended in the current guidelines can enhance the Helicobacter pylori (H. pylori) eradication rate and decrease the incidence of adverse events. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue. Methods: We performed comprehensive searches in PubMed, Embase, Web of Science, and Cochrane library databases from the inception of the databases through to November 1, 2023. A meta-analysis was conducted to determine the pooled relative risk (RR) with 95% confidence intervals (CI) using a random-effects model. We utilized the revised Cochrane Risk of Bias Tool to assess the risk of bias of included studies. Results: A total of six RCTs (1,404 patients) included in this meta-analysis. The results of the intention-to-treat analysis showed that the combination of S. boulardii with BQT had a higher eradication rate than BQT alone (87.0% versus 83.3%), with a pooled RR of 1.05 (95% CI: 1.00-1.10, p = 0.03). In the per-protocol analysis, however, there was no statistical significance between the two groups in the eradication rate (93.7% versus 91.0%, RR = 1.03, 95% CI: 1.00-1.06, p = 0.07). The combination of S. boulardii and BQT had a significantly lower rate of overall adverse events (22% vs. 39%, RR = 0.56, 95% CI: 0.44-0.70, p < 0.00001), diarrhea (7.9% vs. 25.7%, RR = 0.29, 95% CI: 0.17-0.48, p < 0.00001), constipation (2.9% vs. 8.4%, RR = 0.35, 95% CI: 0.14-0.88, p = 0.03) and abdominal distention (4.9% vs. 12.7%, RR = 0.41, 95% CI: 0.23-0.72, p = 0.002) than BQT alone. For the assessment of risk of bias, five studies were deemed to have some concerns, while one study was judged to have a low risk. Conclusion: Current evidence suggests that supplementation with S. boulardii in BQT may not have a major effect on the H. pylori eradication rate, but significantly reduces the incidence of overall adverse events, diarrhea, abdominal distention and constipation. Combining S. Boulardii with BQT can help alleviate symptoms, potentially improving patient adherence. Systematic review registration: https://osf.io/n9z7c.

8.
Bioresour Technol ; 377: 128935, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36958683

RESUMO

This study aimed to elucidate the multiple strategies employed by anaerobes during granulation in a laboratory upflow anaerobic sludge blanket reactor, based on microbial succession and interactions. The anaerobic granulation process featured staged dominance of microbial genera, corresponding well with the environmental traits. Across the stages (selection, seeding, expansion, and maturation), chemotaxis attraction of nitrogen and/or carbon sources and flagellar motion were the primary strategy of microbial assembly. The second messengers - cyclic adenosine and guanosine monophosphates - partially regulated the agglomeration of filamentous Euryachaeota and Chloroflexi as the inner cores, while quorum sensing mediated the expansion of granules prior to maturation. Antagonism or competition governed the interactions within the phylogenetic molecular ecological network during sludge granulation, which were largely driven by the low-abundance (<1%) taxa. These new insights suggest that better engineering solutions to enhance chemotaxis attraction and species selection could achieve more efficient anaerobic granular sludge processes.


Assuntos
Reatores Biológicos , Esgotos , Anaerobiose , Filogenia , Bactérias Anaeróbias
9.
Nat Commun ; 14(1): 4975, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37591830

RESUMO

Iron-based catalysts are promising candidates for advanced oxidation process-based wastewater remediation. However, the preparation of these materials often involves complex and energy intensive syntheses. Further, due to the inherent limitations of the preparation conditions, it is challenging to realise the full potential of the catalyst. Herein, we develop an iron-based nanomaterial catalyst via soft carbon assisted flash joule heating (FJH). FJH involves rapid temperature increase, electric shock, and cooling, the process simultaneously transforms a low-grade iron mineral (FeS) and soft carbon into an electron rich nano Fe0/FeS heterostructure embedded in thin-bedded graphene. The process is energy efficient and consumes 34 times less energy than conventional pyrolysis. Density functional theory calculations indicate that the electron delocalization of the FJH-derived heterostructure improves its binding ability with peroxydisulfate via bidentate binuclear model, thereby enhancing ·OH yield for organics mineralization. The Fe-based nanomaterial catalyst exhibits strong catalytic performance over a wide pH range. Similar catalysts can be prepared using other commonly available iron precursors. Finally, we also present a strategy for continuous and automated production of the iron-based nanomaterial catalysts.

10.
Medicine (Baltimore) ; 100(42): e27569, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678897

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is 1 of the most serious complications of diabetes mellitus and the leading cause of end-stage renal disease in the world. Huangkui capsule, extracted from Abelmoschus manihot (L.) medic (AM), has been widely used to treat DN. However, there is no consensus on the efficacy of Huangkui capsule for DN. This study aims to perform meta-analysis to systematically review the efficacy and safety of Huangkui capsule. METHODS: The following 9 electronic databases will be comprehensively searched: PubMed, web of science, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang data, and Chinese BioMedicine Literature Database. The retrieval time is from their inception to May 2021. According to the inclusion and exclusion criteria, 2 reviewers independently completed the study selection, data extraction, risk of bias assessment, and data synthesis. Review Manager Version 5.3 software will be used to conduct meta-analysis. RESULTS: This study provides a high-quality synthesis to assess the efficacy of Huangkui capsule for treating diabetic nephropathy. CONCLUSION: The result of this systematic review will provide objective evidence-based basis to judge the effectiveness and safety of Huangkui capsule on diabetic nephropathy.


Assuntos
Abelmoschus , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Extratos Vegetais/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Metanálise como Assunto
11.
Sci Rep ; 11(1): 20849, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675276

RESUMO

This study systematically explored the underlying mechanism of Rhizoma Coptidis against type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking and experimental validation. We retrieved and screened active compounds of Rhizoma Coptidis and corresponding T2DM-related targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened via topological analysis. GO and KEGG enrichment analyses were performed by using DAVID. Finally, molecular docking and experimental studies were performed after bioinformatic analysis for verification. There were 14 active compounds and 19 core targets of Rhizoma Coptidis-T2DM, of which quercetin was identified as the main compound and IL6, VEGFA and TNF were the most significant core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis ameliorated T2DM by regulating multiple biological processes and pathways. Docking studies indicated that IL6, VEGFA and TNF could stably bind with all active compounds of Rhizoma Coptidis. The results of our experiments revealed that Rhizoma Coptidis could inhibit the expression of IL6 and TNFα and enhance islet cell viability. This study suggests anti-inflammatory therapeutic effects of Rhizoma Coptidis on T2DM, thereby providing a scientific basis and new insight for further research on the antidiabetic effect of Rhizoma Coptidis.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Farmacologia em Rede , Coptis chinensis/química , Diabetes Mellitus Tipo 2/metabolismo , Medicamentos de Ervas Chinesas/química , Humanos , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas/efeitos dos fármacos , Quercetina/química , Quercetina/farmacologia
12.
Cells ; 10(11)2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34831185

RESUMO

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.


Assuntos
Doenças do Sistema Nervoso Central/enzimologia , Doenças do Sistema Nervoso Central/patologia , Sistema Nervoso Central/enzimologia , Sistema Nervoso Central/patologia , Fosfolipases A2 Secretórias/metabolismo , Vesículas Extracelulares/enzimologia , Humanos , Peroxidação de Lipídeos , Lipidômica , Fosfolipases A2 Secretórias/química
13.
Healthcare (Basel) ; 9(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374838

RESUMO

In the era of artificial intelligence, big data and 5G, health care for elderly people is facing an important digital transformation. The objective of this study is to design the data analysis module of the elderly health service monitoring system (HSMS) and attempt to put forward a new healthy aging (HA) model that is applicable not only to the individual HA, but also to the regional HA system. Based on the HA theory of collaborative governance, we divided the elderly HSMS into four modules, including physical health, mental health, ability of daily activity, and social participation. Then, factors that influence HA were assessed by stepwise logistic regression to build the analysis model, using the public micro-panel data of the China Health and Retirement Longitudinal Survey (CHARLS). Age (odds ratio (OR) = 1.55 (95% confidence interval (CI): 1.06-2.27)), living in urban areas (OR = 1.57 (95% CI: 1.03-2.39)), being literate (OR = 1.51 (95% CI: 1.01-2.23)), expecting to get long-term health care in the future from their grown children (OR = 1.69 (95% CI: 1.10-2.61)) and having literate grown children (OR = 2.01 (95% CI: 0.26-0.97)) had a significant positive impact on HA of elderly people. Therefore, the F-W (factors and weighs, also family and welfare) model is proposed in this paper. The outcomes can contribute with designing HSMS for different provinces and several different regions in China and leave a door open to improve the model and algorithm application for HSMS in the future studies.

14.
Mol Neurobiol ; 57(2): 1085-1098, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677009

RESUMO

Growing evidence suggests that docosahexaenoic acid (DHA) exerts neuroprotective effects, although the mechanism(s) underlying these beneficial effects are not fully understood. Here we demonstrate that DHA, but not arachidonic acid (ARA), suppressed oligomeric amyloid-ß peptide (oAß)-induced reactive oxygen species (ROS) production in primary mouse microglia and immortalized mouse microglia (BV2). Similarly, DHA but not ARA suppressed oAß-induced increases in phosphorylated cytosolic phospholipase A2 (p-cPLA2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) in BV2 cells. LC-MS/MS assay indicated the ability for DHA to cause an increase in 4-hydroxyhexenal (4-HHE) and suppress oAß-induced increase in 4-hydroxynonenal (4-HNE). Although oAß did not alter the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, exogenous DHA, ARA as well as low concentrations of 4-HHE and 4-HNE upregulated this pathway and increased production of heme oxygenase-1 (HO-1) in microglial cells. These results suggest that DHA modulates ARA metabolism in oAß-stimulated microglia through suppressing oxidative and inflammatory pathways and upregulating the antioxidative stress pathway involving Nrf2/HO-1. Understanding the mechanism(s) underlying the beneficial effects of DHA on microglia should shed light into nutraceutical therapy for the prevention and treatment of Alzheimer's disease (AD).


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Microglia/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ácido Araquidônico/metabolismo , Ácido Araquidônico/farmacologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Espectrometria de Massas em Tandem/métodos
15.
ACS Chem Neurosci ; 10(1): 209-215, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30399318

RESUMO

Cerebral amyloid angiopathy (CAA), a condition depicting cerebrovascular accumulation of amyloid ß-peptide (Aß), is a common pathological manifestation in Alzheimer's disease (AD). In this study, we investigated the effects of Azelnidipine (ALP), a dihydropyridine calcium channel blocker known for its treatment of hypertension, on oligomeric Aß (oAß)-induced calcium influx and its downstream pathway in immortalized mouse cerebral endothelial cells (bEND3). We found that ALP attenuated oAß-induced calcium influx, superoxide anion production, and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and calcium-dependent cytosolic phospholipase A2 (cPLA2). Both ALP and cPLA2 inhibitor, methylarachidonyl fluorophosphate (MAFP), suppressed oAß-induced translocation of NFκB p65 subunit to nuclei, suggesting that cPLA2 activation and calcium influx are essential for oAß-induced NFκB activation. In sum, our results suggest that calcium channel blocker could be a potential therapeutic strategy for suppressing oxidative stress and inflammatory responses in Aß-stimulated microvasculature in AD.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Ácido Azetidinocarboxílico/análogos & derivados , Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Células Endoteliais/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/fisiologia , Animais , Ácido Azetidinocarboxílico/farmacologia , Linhagem Celular Transformada , Angiopatia Amiloide Cerebral/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Células Endoteliais/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
16.
Mol Neurobiol ; 56(5): 3222-3234, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30112630

RESUMO

Cytosolic phospholipase A2 (cPLA2) mediates oligomeric amyloid-ß peptide (oAß)-induced oxidative and inflammatory responses in glial cells. Increased activity of cPLA2 has been implicated in the neuropathology of Alzheimer's disease (AD), suggesting that cPLA2 regulation of oAß-induced microglial activation may play a role in the AD pathology. We demonstrate that LPS, IFNγ, and oAß increased phosphorylated cPLA2 (p-cPLA2) in immortalized mouse microglia (BV2). Aß association with primary rat microglia and BV2 cells, possibly via membrane-binding and/or intracellular deposition, presumably indicative of microglia-mediated clearance of the peptide, was reduced by inhibition of cPLA2. However, cPLA2 inhibition did not affect the depletion of this associated Aß when cells were washed and incubated in a fresh medium after oAß treatment. Since the depletion was abrogated by NH4Cl, a lysosomal inhibitor, these results suggested that cPLA2 was not involved in the degradation of the associated Aß. To further dissect the effects of cPLA2 on microglia cell membranes, atomic force microscopy (AFM) was used to determine endocytic activity. The force for membrane tether formation (Fmtf) is a measure of membrane-cytoskeleton connectivity and represents a mechanical barrier to endocytic vesicle formation. Inhibition of cPLA2 increased Fmtf in both unstimulated BV2 cells and cells stimulated with LPS + IFNγ. Thus, increasing p-cPLA2 would decrease Fmtf, thereby increasing endocytosis. These results suggest a role of cPLA2 activation in facilitating oAß endocytosis by microglial cells through regulation of the membrane-cytoskeleton connectivity.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Membrana Celular/metabolismo , Citoesqueleto/metabolismo , Microglia/metabolismo , Fosfolipases A2 Citosólicas/metabolismo , Multimerização Proteica , Animais , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Citoesqueleto/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Interferon gama/farmacologia , Cinética , Lipopolissacarídeos/farmacologia , Camundongos , Fosfolipases A2 Citosólicas/antagonistas & inibidores , Ratos
17.
Chemosphere ; 231: 225-232, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129403

RESUMO

To investigate the associations between prenatal exposure to single metal and multiple metals and the risk of low birth weight (LBW), we conducted a nested case-control study of 246 LBW and 406 NBW mother-infant pairs based on a prospective birth cohort study. 22 serum metals were detected by inductively coupled plasma quadruple mass spectrometry (ICP-MS). Categorical analyses showed serum Co and Ti were associated with LBW (Co: 3rd vs 4th. quartile: OR = 1.83, 95%CI: 1.14-2.92, Ptrend = 0.043; Ti: 2nd vs. 4th quartile: OR = 0.51, 95% CI: 0.32-0.81, P trend = 0.051), especially gestational age >13 weeks (Co: 3rd vs. 4th quartile: OR = 1.94, 95% CI: 1.13 - 3.32, Ptrend = 0.043; Ti: 2nd vs. 4th quartile: OR = 0.50, 95% CI: 0.30 - 0.84, P trend= 0.073). Cubic spline analyses showed serum Co and serum Ti had non-linearity associations with LBW (Co: P for overall = 0.048, P-nonlinearity = 0.014; Ti: P for overall = 0.015, P- nonlinearity = 0.008). In multi-metal compound exposure model, 15 metals selected by elastic net model were significantly associated with the increased risk of LBW and OR (95%CI) was 5.14 (2.81-9.40). Our study suggested that lower level serum Co was positively associated with LBW and lower level serum Ti was negatively associated with LBW, especially gestational age >13 weeks, and both of them had non-linearity dose-relationships with LBW. And multi-metal compound model was significantly associated with LBW compared with single metal model.


Assuntos
Poluentes Ambientais/sangue , Recém-Nascido de Baixo Peso/metabolismo , Exposição Materna/estatística & dados numéricos , Metais/sangue , Adulto , Peso ao Nascer , Estudos de Casos e Controles , China , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Mães , Gravidez , Estudos Prospectivos , Adulto Jovem
18.
Sci Rep ; 8(1): 10771, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018374

RESUMO

The study aimed to investigate the associations between maternal lifestyles and antenatal stress and anxiety. 1491 pregnant women were drawn from the Guangxi birth cohort study (GBCS). A base line questionnaire was used to collect demographic information and maternal lifestyles. The Pregnancy Stress Rating Scale (PSRS) and Self-Rating Anxiety Scale (SAS) were used to assess prenatal stress and anxiety, respectively. Regression analyses identified the relationship between maternal lifestyles and prenatal stress and anxiety: (1) Hours of phone use per day was positively correlated to prenatal stress and anxiety and increased with stress and anxiety levels (all P trend < 0.05). In addition, not having baby at home was positively correlated to prenatal stress. (2) Self-reported sleep quality was negative with prenatal stress and anxiety, and decreased with stress and anxiety levels (all P trend < 0.01). Moreover, not frequent cooking was negatively correlated to prenatal stress and having pets was negatively correlated to prenatal anxiety (P < 0.05). However, having pets was not correlated to prenatal stress (P > 0.05). Our results showed that adverse lifestyles increase the risk of antenatal stress and anxiety, a regular routine and a variety of enjoyable activities decreases the risk of prenatal stress and anxiety.


Assuntos
Ansiedade , Estilo de Vida , Gestantes/psicologia , Estresse Psicológico , Adulto , China , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Gravidez , Autorrelato
19.
PLoS One ; 12(10): e0186135, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29045415

RESUMO

The morphology and the drug sensitivity of the strain GYX2014-1 isolated from the hepatic pancreatic tissue of moribund Litopenaeus vannamei were evaluated by conventional culture characteristics, physical and chemical characteristics, and molecular biology methods. Detection of extracellulase and hemolysin activity shows that the isolated GYX2014-1 has protease, lipase, gelatinase activity, but none of amylase, or lecithinase activity. The 16S rRNA gene (GenBank accession number: KT781675) was analyzed, and a phylogenetic tree analysis showed that the isolated pathogen was most closely related to V. vulnificus (GenBank accession number: NR 118570)-a match of more than 99%. The phenotypic traits and molecular biology of isolated bacteria, determined their identity as Vibrio vulnificus (V. vulnificus). In addition, artificially infected L. vannamei with Vibrio vulnificus appeared with the same disease symptoms as those of naturally infected shrimp. Drug sensitivity tests showed that V. vulnificus is highly sensitive to fosfomycin, cefradine and sinomin, and was resistant to penicillin, amikacin and kanamycin. This experiment is the first to separate V. vulnificus from L. vannamei, and the findings of this study can be used as a reference for disease control and health management.


Assuntos
Penaeidae/virologia , Vibrio vulnificus/genética , Vibrio vulnificus/isolamento & purificação , Animais , Sequência de Bases , Contagem de Colônia Microbiana , Espaço Extracelular/enzimologia , Testes de Sensibilidade Microbiana , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Vibrioses/microbiologia
20.
PLoS One ; 12(2): e0170346, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28170408

RESUMO

Occludin is a key tight junction (TJ) protein in cerebral endothelial cells (CECs) playing an important role in modulating blood-brain barrier (BBB) functions. This protein (65kDa) has been shown to engage in many signaling pathways and phosphorylation by both tyrosine and threonine kinases. Despite yet unknown mechanisms, pro-inflammatory cytokines and endotoxin (lipopolysaccharides, LPS) may alter TJ proteins in CECs and BBB functions. Here we demonstrate the responses of occludin in an immortalized human cerebral endothelial cell line (hCMEC/D3) to stimulation by TNFα (10 ng/mL), IL-1ß (10 ng/mL) and LPS (100 ng/mL). Exposing cells to TNFα resulted in a rapid and transient upward band-shift of occludin, suggesting of an increase in phosphorylation. Exposure to IL-1ß produced significantly smaller effects and LPS produced almost no effects on occludin band-shift. TNFα also caused transient stimulation of p38MAPK and ERK1/2 in hCMEC/D3 cells, and the occludin band-shift induced by TNFα was suppressed by SB202190, an inhibitor for p38MAPK, and partly by U0126, the MEK1/2-ERK1/2 inhibitor. Cells treated with TNFα and IL-1ß but not LPS for 24 h resulted in a significant (p < 0.001) decrease in the expression of occludin, and the decrease could be partially blocked by SB202190, the inhibitor for p38MAPK. Treatment with TNFα also altered cell morphology and enhanced permeability of the CEC layer as measured by the FITC-dextran assay and the trans-endothelial electrical resistances (TEER). However, treatment with SB202190 alone could not effectively reverse the TNFα -induced morphology changes or the enhanced permeability changes. These results suggest that despite effects of TNFα on p38MAPK-mediated occludin phosphorylation and expression, these changes are not sufficient to avert the TNFα-induced alterations on cell morphology and permeability.


Assuntos
Córtex Cerebral/metabolismo , Células Endoteliais/metabolismo , Ocludina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Eletrofisiológicos , Expressão Gênica , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ocludina/genética , Permeabilidade , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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