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1.
Pest Manag Sci ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523221

RESUMO

BACKGROUND: The use of chemical insecticides to control Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) is widespread, although it might exert a sublethal effect on its dominant parasitoid, Encarsia formosa Gahan (Hymenoptera: Aphelinidae). To investigate the sublethal effect of spirotetramat on E. formosa, we observed the ability of E. formosa to locate and handle the host, oviposit and preen after exposure to sublethal concentrations of spirotetramat. RESULTS: After exposure to spirotetramat at LC50 , the response time of E. formosa to the volatile reached 223.40 s and was significantly prolonged. Only 56.44% of the wasps were attracted by the volatile and the insect crawled the slowest among all of the treatments. The averages of oviposition posture adopted and host handled by each E. formosa in 1 h decreased significantly to 1.79 and 1.27, respectively. At the sublethal concentration of LC10 , 94.59% of the wasps were attracted by the volatile and the insect crawled the fastest. The average of host handled by each E. formosa was 3.92, and the frequency of drumming while walking and drumming the host was 12.34 times per second and 12.30 times per second, respectively, demonstrating a significant acceleration in these abilities. CONCLUSION: These findings demonstrate that spirotetramat induced hormesis in E. formosa on exposure to its LC10 concentration and accelerated its host locating, host handling and frequency of antennae drumming. These findings could assist in balancing the chemical and biological control of B. tabaci and enhancing the efficacy of E. formosa as a biocontrol agent.

2.
Dalton Trans ; 50(35): 12215-12225, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34396380

RESUMO

A series of homodinuclear ß-diketone lanthanide(III) complexes, formulated as [(acac)4Ln2(L1)] (Ln3+ = Dy3+ (1), Tb3+ (2), and Gd3+ (3), respectively) were first synthesized based on a closed-macrocyclic ligand (H2L1) derived from the [2 + 2] cyclocondensation of 4-tert-butyl-2,6-diformylphenol and o-phenylenediamine in the presence of lanthanide acetylacetonates. Subsequently, by using the above compounds as building blocks to assemble directly with another Schiff base ligand, N,N'-bis(5-chlorosalicylidene)-o-phenylenediamine (H2L2), three new homodinuclear sandwich-type lanthanide complexes with the general formula [Ln2(L1)(L2)2] (Ln3+ = Dy3+ (4), Tb3+ (5), and Gd3+ (6), respectively) were further designed and prepared. Single-crystal X-ray analyses show that the central Ln3+ ion adopts a distorted square antiprism conformation with D4d local symmetry. Magnetic studies reveal ferromagnetic interaction between Dy3+ and Tb3+ centres and zero-field slow relaxation of magnetization for Dy complexes 1 and 4. The corresponding magneto-structural correlations of SMMs 1 and 4 were further discussed by theoretical calculations and with experimental outcomes.

3.
Environ Sci Technol ; 55(17): 11557-11567, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34431667

RESUMO

The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Oxigênio , Material Particulado/análise , SARS-CoV-2
4.
Anal Chem ; 93(27): 9568-9574, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34210120

RESUMO

In this work, an original rolling-circle strand displacement amplification (RC-SDA) was developed by introducing a circle DNA with two recognition domains as a template instead of the limited liner DNA template in traditional strand displacement amplification (SDA), which displayed much shorter reaction time down to 30 min and quite higher conversion efficiency of more than 1.77 × 108 compared with those of traditional strand displacement amplification (SDA) and could be applied to construct a label-free biosensor for ultrasensitive detection of an HIV DNA fragment. Once the target HIV DNA fragment interacts with the template circle DNA, the RC-SDA could be activated to dramatically output amounts of mimic target DNA with the assistance of the Phi29 DNA polymerase and Nb.BbvCI enzyme. In application, while the output products were captured by the DNA tetrahedral nanoprobe (DTNP) modified electrode, the electrochemical tag silver nanoclusters (AgNCs) on DTNP would be released from the electrode surface, accompanied with an obviously decreased electrochemical signal. This way, the developed signal-off biosensor was successfully applied to realize the rapid and ultrasensitive detection of target HIV DNA fragment with a detection limit down to 0.21 fM, which exploits the new generation of a universal strategy beyond the traditional ones for applications in biosensing assay, clinic diagnosis, and DNA nanobiotechnology.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , DNA/genética , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico , Prata
5.
Mol Ther Methods Clin Dev ; 21: 299-314, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-33898629

RESUMO

Antigen-specific lung-resident memory T cells (TRMs) constitute the first line of defense that mediates rapid protection against respiratory pathogens and inspires novel vaccine designs against infectious pandemic threats, yet effective means of inducing TRMs, particularly via non-viral vectors, remain challenging. Here, we demonstrate safe and potent induction of lung-resident TRMs using a biodegradable polymeric nanoshell that co-encapsulates antigenic peptides and TLR9 agonist CpG-oligodeoxynucleotide (CpG-ODN) in a virus-mimicking structure. Through subcutaneous priming and intranasal boosting, the combinatorial nanoshell vaccine elicits prominent lung-resident CD4+ and CD8+ T cells that surprisingly show better durability than live viral infections. In particular, nanoshells containing CpG-ODN and a pair of conserved class I and II major histocompatibility complex-restricted influenza nucleoprotein-derived antigenic peptides are demonstrated to induce near-sterilizing immunity against lethal infections with influenza A viruses of different strains and subtypes in mice, resulting in rapid elimination of replicating viruses. We further examine the pulmonary transport dynamic and optimal composition of the nanoshell vaccine conducive for robust TRM induction as well as the benefit of subcutaneous priming on TRM replenishment. The study presents a practical vaccination strategy for inducing protective TRM-mediated immunity, offering a compelling platform and critical insights in the ongoing quest toward a broadly protective vaccine against universal influenza as well as other respiratory pathogens.

6.
Nano Lett ; 20(4): 2246-2256, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32160474

RESUMO

Many favorable anticancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which results in the release of endogenous danger signals along with tumor antigens for effective priming of anticancer immunity. We describe a strategy to artificially induce ICD by delivering the agonist of stimulator of interferon genes (STING) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris that spatiotemporally coordinate tumor antigens and STING agonist in a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics and enables colocalization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and anticancer adaptive response. In three mouse tumor models, sICD enhances therapeutic efficacy and restrains tumor progression. The study highlights the benefit of delivering STING agonists to cancer cells, paving ways to new chemo-immunotherapeutic designs.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Proteínas de Membrana/agonistas , Nanoconchas/uso terapêutico , Neoplasias/terapia , Animais , Antineoplásicos Imunológicos/administração & dosagem , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Imunoterapia , Camundongos Endogâmicos BALB C , Nanoconchas/administração & dosagem , Neoplasias/imunologia
7.
World J Gastroenterol ; 26(6): 645-656, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103873

RESUMO

BACKGROUND: Reports on bacterial infection (BI) in decompensated cirrhosis (DC) is mainly from alcoholic cirrhosis. The role of BI as a trigger or complication of acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus decompensated cirrhosis (HBV-DC) remains to be investigated. AIM: To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF. METHODS: This retrospective study included patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event. RESULTS: A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82). CONCLUSION: BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival. HBV-DC patients should be monitored carefully for the development of BI, especially pneumonia, to avoid an adverse outcome.


Assuntos
Insuficiência Hepática Crônica Agudizada/mortalidade , Infecções Bacterianas/mortalidade , Vírus da Hepatite B , Hepatite B Crônica/mortalidade , Cirrose Hepática/mortalidade , Insuficiência Hepática Crônica Agudizada/microbiologia , Adulto , Infecções Bacterianas/complicações , China , Feminino , Hepatite B Crônica/microbiologia , Humanos , Cirrose Hepática/microbiologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
8.
Virulence ; 11(1): 145-158, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32043433

RESUMO

Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems.To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs.We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1ß, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Ceftazidima/farmacologia , Imipenem/farmacologia , Membranas/efeitos dos fármacos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/mortalidade , Animais , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Óxido Nítrico Sintase/metabolismo , Proteômica , Células RAW 264.7
9.
Dalton Trans ; 48(35): 13360-13368, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432059

RESUMO

Four novel homoleptic triple-decker lanthanide complexes, [Ln2(L)(Cl-salphen)2]·0.5ClCH2CH2Cl (Ln3+ = Gd3+ (1), Ho3+ (2), Tb3+ (3), and Dy3+ (4)), have been designed and synthesized based on a Schiff base ligand N,N'-bis(5-chlorosalicylidene)-o-phenylenediamine (Cl-salphenH2) and the building blocks [(acac)4Ln2(L)]; these complexes were derived from a closed-macrocyclic ligand (H2L) obtained by the [2 + 2] template condensation of 2,6-diformyl-4-methylphenol and 1,3-diaminopropane in the presence of lanthanide acetylacetonates. Single-crystal X-ray analyses show that central Ln3+ ions adopt distorted square antiprism conformations with D4d symmetry. Theoretical analysis and magnetic measurements reveal that Dy complex 4 behaves as a typical SMM with the characteristics of slow magnetic relaxation behavior and intermetallic ferromagnetic interaction.

10.
Nat Commun ; 10(1): 1057, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837473

RESUMO

Cell membranes are an intricate yet fragile interface that requires substrate support for stabilization. Upon cell death, disassembly of the cytoskeletal network deprives plasma membranes of mechanical support and leads to membrane rupture and disintegration. By assembling a network of synthetic hydrogel polymers inside the intracellular compartment using photo-activated crosslinking chemistry, we show that the fluid cell membrane can be preserved, resulting in intracellularly gelated cells with robust stability. Upon assessing several types of adherent and suspension cells over a range of hydrogel crosslinking densities, we validate retention of surface properties, membrane lipid fluidity, lipid order, and protein mobility on the gelated cells. Preservation of cell surface functions is further demonstrated with gelated antigen presenting cells, which engage with antigen-specific T lymphocytes and effectively promote cell expansion ex vivo and in vivo. The intracellular hydrogelation technique presents a versatile cell fixation approach adaptable for biomembrane studies and biomedical device construction.

11.
Adv Funct Mater ; 29(28): 1807616, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32313544

RESUMO

The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus-like fashion. STING agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH-responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoV-permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle-based MERS-CoV vaccine are protected against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.

12.
Acta Biomater ; 82: 133-142, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30316023

RESUMO

Amidst the ever-rising threat of antibiotics resistance, colistin, a decade-old antibiotic with lingering toxicity concern, is increasingly prescribed to treat many drug-resistant, gram-negative bacteria. With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. Subsequent stabilization by DSPE-PEG and homogenization through micro-fluidization of the liquid coacervates yielded nanoparticles 8 nm in diameter. In vitro assessment showed that the colistin antimicrobial activity against multiple drug-resistant bacterial strains was retained and, in some cases, enhanced following the nanoparticle assembly. In vivo administration in mice demonstrated improved safety of the colistin nanoparticle, which has a maximal tolerated dose of 12.5 mg/kg compared to 10 mg/kg of free colistin. Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin. In mouse models of Klebsiella pneumoniae bacteremia and Acinetobacter baumannii pneumonia, treatment with colistin nanoparticles showed equivalent efficacy to free colistin. These results demonstrate coacervation-induced nanoparticle assembly as a promising approach towards improving colistin treatments against bacterial infections. STATEMENT OF SIGNIFICANCE: Improving the safety of colistin while retaining its antimicrobial activity has been a highly sought-after objective toward enhancing antibacterial treatments. Herein, we demonstrate formation of stabilized colistin nanocomplexes in the presence of anionic polypeptides and DSPE-PEG stabilizer. The nanocomplexes retain colistin's antimicrobial activity while demonstrating improved safety upon in vivo administration. The supramolecular nanoparticle assembly of colistin presents a unique approach towards designing antimicrobial nanoparticles.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii/metabolismo , Bacteriemia , Colistina , Infecções por Klebsiella , Klebsiella pneumoniae/metabolismo , Nanopartículas , Pneumonia Bacteriana , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/metabolismo , Animais , Bacteriemia/tratamento farmacológico , Bacteriemia/metabolismo , Colistina/química , Colistina/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/metabolismo
13.
Arterioscler Thromb Vasc Biol ; 38(5): e71-e84, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29599140

RESUMO

OBJECTIVE: B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. APPROACH AND RESULTS: Using mixed chimeric Ldlr-/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr-/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. CONCLUSIONS: The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications.


Assuntos
Aterosclerose/imunologia , Linfócitos B/imunologia , Diferenciação Celular , Centro Germinativo/imunologia , Imunoglobulina G/imunologia , Plasmócitos/imunologia , Linfócitos T/imunologia , Animais , Apoptose , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Linfócitos B/metabolismo , Antígenos CD40/genética , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Centro Germinativo/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Imunoglobulina G/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Necrose , Fenótipo , Placa Aterosclerótica , Plasmócitos/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/imunologia , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Receptores de LDL/deficiência , Receptores de LDL/genética , Via Secretória , Transdução de Sinais , Linfócitos T/metabolismo
14.
Dis Aquat Organ ; 125(3): 207-215, 2017 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-28792419

RESUMO

Heat shock protein 60 from the Chinese mitten crab Eriocheir sinensis (EsHSP60) was previously identified in relation to Spiroplasma eriocheiris infection by isobaric tags for relative and absolute quantitation labelling followed by liquid chromatography-tandem mass spectrometry. In the present study, to validate the immune function of this protein, the cDNA of the EsHSP60 gene was cloned. Various crab tissues were assessed using real-time PCR, which showed that EsHSP60 transcription occurred in all tissues examined. The expression profiles of EsHSP60 in haemolymph at transcription and protein levels when infected with S. eriocheiris were investigated by real-time PCR and Western blot analysis, respectively. A significant increase of EsHSP60 transcription and protein expression appeared post-injection in response to S. eriocheiris infection when compared to the control group. The double-luciferase reporter gene assay showed that the microRNA PC-533-3p interacted with the 3'-untranslated region of EsHSP60 and inhibited the translation of EsHSP60. The expression profiles of PC-533-3p during S. eriocheiris infection were also investigated by real-time PCR. However, the change tendency of PC-533-3p was opposite to that of the EsHSP60 after S. eriocheiris challenge. These data indicate that the EsHSP60 proteins may play an important role in mediating the immune responses of E. sinensis to an S. eriocheiris challenge.


Assuntos
Braquiúros/microbiologia , Chaperonina 60/metabolismo , Regulação da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Spiroplasma/fisiologia , Animais , Braquiúros/genética , Braquiúros/metabolismo , Chaperonina 60/genética , Brânquias/metabolismo , Hemócitos/metabolismo , Hemolinfa , Hepatopâncreas/metabolismo , Interações Hospedeiro-Patógeno , Mucosa Intestinal/metabolismo , MicroRNAs/genética , Músculos/metabolismo , Miocárdio/metabolismo , Neurônios/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Int J Mol Sci ; 18(4)2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-28387707

RESUMO

Coffea arabica extract (CAE) containing 48.3 ± 0.4 mg/g of chlorogenic acid and a trace amount of caffeic acid was found to alleviate photoaging activity in human skin fibroblasts. In this study, polyphenol-rich CAE was investigated for its antioxidant and antiinflammatory properties, as well as for its capability to alleviate ultraviolet B (UVB)-induced photodamage in BALB/c hairless mice. The results indicated that 500 µg/mL of CAE exhibited a reducing power of 94.7%, ferrous ion chelating activity of 46.4%, and hydroxyl radical scavenging activity of 20.3%. The CAE dose dependently reduced UVB-induced reactive oxygen species (ROS) generation in fibroblasts. Furthermore, CAE inhibited the UVB-induced expression of cyclooxygenase-2 and p-inhibitor κB, and the translocation of nuclear factor-kappa B (NF-κB) to the nucleus of fibroblasts. In addition, CAE alleviated UVB-induced photoaging and photodamage in BALB/c hairless mice by restoring the collagen content and reduced UVB-induced epidermal hyperplasia. CAE also inhibited UVB-induced NF-κB, interleukin-6, and matrix metalloproteinase-1 expression in the hairless mouse skin. The results indicated that CAE exhibits antiphotodamage activity by inhibiting UV-induced oxidative stress and inflammation. Therefore, CAE is a candidate for use in antioxidant, antiinflammatory, and antiphotodamage products.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Coffea/química , Fibroblastos/efeitos dos fármacos , Polifenóis/administração & dosagem , Radiodermatite/prevenção & controle , Administração Tópica , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Células Cultivadas , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Pelados , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Radiodermatite/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Cardiovasc Res ; 111(4): 385-97, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27492217

RESUMO

AIMS: B2 lymphocytes promote atherosclerosis development but their mechanisms of action are unknown. Here, we investigated the role of tumour necrosis factor alpha (TNF-α) produced by B2 cells in atherogenesis. METHODS AND RESULTS: We found that 50% of TNF-α-producing spleen lymphocytes were B2 cells and ∼20% of spleen and aortic B cells produced TNF-α in hyperlipidemic ApoE(-/-) mice. We generated mixed bone marrow (80% µMT/20% TNF-α(-/-)) chimeric LDLR(-/-) mice where only B cells did not express TNF-α. Atherosclerosis was reduced in chimeric LDLR(-/-) mice with TNF-α-deficient B cells. TNF-α expression in atherosclerotic lesions and in macrophages were also reduced accompanied by fewer apoptotic cells, reduced necrotic cores, and reduced lesion Fas, interleukin-1ß and MCP-1 in mice with TNF-α-deficient B cells compared to mice with TNF-α-sufficient B cells. To confirm that the reduced atherosclerosis is attributable to B2 cells, we transferred wild-type and TNF-α-deficient B2 cells into ApoE(-/-) mice deficient in B cells or in lymphocytes. After 8 weeks of high fat diet, we found that atherosclerosis was increased by wild-type but not TNF-α-deficient B2 cells. Lesions of mice with wild-type B2 cells but not TNF-α-deficient B2 cells also had increased apoptotic cells and necrotic cores. Transferred B2 cells were found in lesions of recipient mice, suggesting that TNF-α-producing B2 cells promote atherosclerosis within lesions. CONCLUSION: We conclude that TNF-α produced by B2 cells is a key mechanism by which B2 cells promote atherogenesis through augmenting macrophage TNF-α production to induce cell death and inflammation that promote plaque vulnerability.


Assuntos
Linfócitos B/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Placa Aterosclerótica/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Aorta/metabolismo , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Morte Celular , Dieta Hiperlipídica , Camundongos Knockout , Fator de Necrose Tumoral alfa/deficiência , Fator de Necrose Tumoral alfa/genética
17.
J Antimicrob Chemother ; 71(12): 3441-3448, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27543656

RESUMO

OBJECTIVES: According to our previous study, OXA-58 translocates to the periplasm via the Sec pathway in carbapenem-resistant Acinetobacter baumannii (CRAb). In the present study, carbapenem-hydrolysing class D ß-lactamases (CHDLs) belonging to the OXA-23, OXA-40 and OXA-51 families were examined to determine whether they are also Sec-dependent. Additionally, the effects of SecA inhibitors combined with carbapenems against CHDL-producing CRAb were examined. METHODS: Cell fractionation and western blot analyses were performed to detect periplasmic His-tagged CHDLs. A chequerboard analysis with pairwise combinations of carbapenems (imipenem or meropenem) and SecA inhibitors (rose bengal, sodium azide or erythrosin B) was performed using six clinical CRAb isolates harbouring different CHDL genes. The fractional inhibitory concentration (FIC) index was determined. The combination with the lowest FIC index was subjected to a time-kill analysis to examine synergistic effects. RESULTS: In an in silico analysis, the CHDLs OXA-23, OXA-40 and OXA-51 were preferentially translocated via the Sec system. The SecA inhibitor rose bengal decreased periplasmic translocation of His-tagged OXA-23 and OXA-83 (belonging to the OXA-51 family), but not OXA-72 (belonging to the OXA-40 family) from ATCC 15151 transformants. Imipenem or meropenem with rose bengal showed synergistic effects (FIC index, ≤0.5) for six and four clinical isolates, respectively. Imipenem or meropenem with sodium azide showed no interactions (FIC index, 0.5-4) against all clinical isolates. Imipenem and rose bengal had the lowest FIC index and showed synergy at 24 h in the time-kill assay. CONCLUSIONS: Combinations of SecA inhibitors and carbapenems have synergistic effects against CHDL-producing CRAb.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Adenosina Trifosfatases/antagonistas & inibidores , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Carbapenêmicos/farmacologia , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Canais de Translocação SEC/antagonistas & inibidores , beta-Lactamases/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Transporte Proteico/efeitos dos fármacos , Proteínas SecA
18.
Dig Liver Dis ; 48(12): 1463-1470, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27575659

RESUMO

BACKGROUND: Hepatocyte death, either apoptosis or necrosis, is closely associated with hepatic inflammation and fibrosis. AIMS: To investigate the potential values of hepatocytes death biomarker, M30 (apoptosis) and M65 (total death) in predicting histological lesions in chronic hepatitis B virus (HBV) infection. METHODS: Total 201 treatment-naïve patients were prospectively recruited. Liver biopsies were performed prior to antiviral treatments for treatments starting evaluation. Sera were collected on the day of liver biopsy for biomarker measurements. Sera from 200 age-matched healthy volunteers served as healthy controls (HCs). RESULTS: Significant histological lesions (SHL, i.e. significant inflammation and/or significant fibrosis) were confirmed in 150 (74.63%) patients. There were significantly higher serum M30 and M65 in patients with SHL than those without SHL (p<0.001) or than HCs (p<0.001). Serum M30, but not M65, independently predicted SHL [odds ratio:3.4 (95% CI, 1.8-6.2) per increase of 50U/L, p<0.001] after adjusting other potential confounding factors. A novel model based on M30 provided good diagnostic performance in predicting SHL [AUC, 0.87 (0.81-0.92)]. Cut-off value of >0 to confirm or ≤-0.5 to exclude SHL has ∼12% misclassification rate. CONCLUSION: Hepatocyte apoptosis biomarker, M30 is a promising non-invasive alternative to liver biopsy in chronic HBV infection upon treatment evaluation.


Assuntos
Apoptose , Hepatite B Crônica/patologia , Hepatócitos/patologia , Queratina-18/sangue , Necrose/sangue , Fragmentos de Peptídeos/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , China , Estudos Transversais , Feminino , Fibrose , Hepatite B Crônica/sangue , Hepatócitos/citologia , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada
19.
Biomed Pharmacother ; 68(7): 833-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25239289

RESUMO

PURPOSE: Observe how specific small RNA interference (siRNA) aimed at TPX2 gene suppresses TPX2 gene expression in esophageal cancer EC9706 cells and the effect on esophageal cancer cell growth and invasion ability. METHODS: Transfect TPX2 siRNA into EC9706 cells via lipofectamin 2000. The experiments were divided into three groups, a negative control, a blank control and an siRNA interference group (24h, 48h, 72h, 96h). We examined RNA and protein level alteration of the TPX2 gene after TPX2 siRNA transfection by RT-PCR and Western blot analysis. Detection of how TPX2 siRNA influences EC9706 cell proliferation was done by MTT, cell apoptosis monitored through Tunel assay, in vitro invasion ability via Boyden chamber and cell cycle change by flow cytometry. RESULTS: After effective siRNA transfection, TPX2 mRNA and protein expression level in siRNA interference group were (0.31±0.08, 0.39±0.12),72h after transfection, significantly lower than blank control group (1.00±0.01) and negative control group (0.98±0.11), (F=71.182, t1=8.17, t2=7.90, P<0.05); MTT results demonstrated that cell growth and proliferation were inhibited and the inhibition rate was up to 35.4% (P<0.05) compared with the control group. TUNEL results indicated that cell apoptosis index in siRNA interference group was 18.28±0.35, higher than that in blank control group (4.07±0.26)and negative control group (4.13±0.22), (F=244.5, t1=60.61, t2=53.32, P<0.01). Boyden chamber results showed that the transmembrane cell number was 45.30±8.08 in siRNA interference group, less than blank control group (121.90±7.83), (F=122.46, t1=11.81, t2=10.47, P<0.01); besides, in siRNA interference group cell invasion inhibition rate was 71.42±9.12, higher than negative control group (5.65±3.55), (t=14.256, P<0.01). Flow cytometry results illustrated that more EC9706 cells went into apoptosis and cell cycle arrested in S phase. Similar results were obtained by in vivo transplantation, as TPX2 siRNA transfection significantly reduced tumor growth of the xenograft in nude mice. CONCLUSION: siRNA could effectively inhibit the invasion and metastasis of EC9706 cells, promote the apoptosis of tumor cells and may become a new approach for treatment of esophageal carcinoma.


Assuntos
Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Proteínas Associadas aos Microtúbulos/genética , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , RNA Interferente Pequeno/genética , Animais , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Interferência de RNA/fisiologia , RNA Mensageiro/genética , Transfecção/métodos
20.
Cytotherapy ; 16(4): 535-44, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24411589

RESUMO

BACKGROUND AIMS: Multiple sclerosis (MS) is considered to be a T-cell-mediated disease. Although MS remits with corticosteroid treatment, the disease relapses on discontinuation of therapy. Human amniotic epithelial cells (hAEC) from the placenta are readily accessible in large quantities and have anti-inflammatory properties. Previously we reported that hAEC given near disease onset ameliorated clinical signs and decreased myelin oligodendrocyte glycoprotein (MOG)-specific immune responses in MOG-induced experimental autoimmune encephalomyelitis (EAE), an experimental MS model. METHODS: To examine the therapeutic effect of hAEC in a clinically relevant setting, we first treated MOG peptide-induced EAE mice with a corticosteroid, prednisolone, in drinking water to induce remission. hAEC were then infused intravenously into the remitted mice. Anti-MOG antibodies in serum were detected by enzyme-linked immunoassay. Splenocyte proliferation was assessed by (3)H-thymidine incorporation. Immune cell subpopulations in spleens and lymph nodes and secreted cytokines in splenocyte culture were quantified by flow cytometry. Central nervous system histology was examined with the use of hematoxylin and eosin, Luxol fast blue and immunostaining. RESULTS: With cessation of prednisolone treatment, hAEC delayed EAE relapse for 7 days, and, after another 7 days, largely remitted disease in six of eight responder mice. Splenocyte proliferation was suppressed, anti-MOG35-55 antibodies in serum were decreased and interleukin-2 and interleukin-5 production by splenocytes were elevated after hAEC treatment. In the central nervous system, hAEC-treated mice had decreased demyelination and fewer macrophages in the inflammatory infiltrates. hAEC treatment also increased CD4(+)CD25(+)FoxP3(+) regulatory T cells in inguinal lymph nodes. CONCLUSIONS: These data demonstrate that the therapeutic effects of hAEC after corticosteroid treatment in an MS model probably are the consequence of peripheral immunoregulation. We suggest that hAEC may have potential as a cell therapy for remitted MS.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Encefalomielite Autoimune Experimental/terapia , Células Epiteliais/transplante , Esclerose Múltipla Recidivante-Remitente/terapia , Líquido Amniótico/citologia , Animais , Anticorpos Anti-Idiotípicos/imunologia , Proliferação de Células/efeitos dos fármacos , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/patologia , Células Epiteliais/citologia , Feminino , Humanos , Camundongos , Esclerose Múltipla Recidivante-Remitente/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/patologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Glicoproteína Mielina-Oligodendrócito/metabolismo , Placenta/citologia , Prednisolona/administração & dosagem , Gravidez
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