Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40.946
Filtrar
1.
BMC Infect Dis ; 20(1): 677, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942991

RESUMO

BACKGROUND: Approximately 80% - 90% of individuals infected with latent Mycobacterium tuberculosis (Mtb) remain protected throughout their life-span. The release of unique, latent-phase antigens are known to have a protective role in the immune response against Mtb. Although the BCG vaccine has been administered for nine decades to provide immunity against Mtb, the number of TB cases continues to rise, thereby raising doubts on BCG vaccine efficacy. The shortcomings of BCG have been associated with inadequate processing and presentation of its antigens, an inability to optimally activate T cells against Mtb, and generation of regulatory T cells. Furthermore, BCG vaccination lacks the ability to eliminate latent Mtb infection. With these facts in mind, we selected six immunodominant CD4 and CD8 T cell epitopes of Mtb expressed during latent, acute, and chronic stages of infection and engineered a multi-epitope-based DNA vaccine (C6). RESULT: BALB/c mice vaccinated with the C6 construct along with a BCG vaccine exhibited an expansion of both CD4 and CD8 T cell memory populations and augmented IFN-γ and TNF-α cytokine release. Furthermore, enhancement of dendritic cell and macrophage activation was noted. Consequently, illustrating the elicitation of immunity that helps in the protection against Mtb infection; which was evident by a significant reduction in the Mtb burden in the lungs and spleen of C6 + BCG administered animals. CONCLUSION: Overall, the results suggest that a C6 + BCG vaccination approach may serve as an effective vaccination strategy in future attempts to control TB.


Assuntos
Vacina BCG/imunologia , Epitopos de Linfócito T , Tuberculose/prevenção & controle , Vacinas de DNA/imunologia , Animais , Antígenos de Bactérias/imunologia , Vacina BCG/genética , Vacina BCG/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/genética , Feminino , Memória Imunológica , Interferon gama/metabolismo , Tuberculose Latente/prevenção & controle , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Vacinas de DNA/farmacologia
2.
J Toxicol Sci ; 45(9): 559-567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879255

RESUMO

Lead is a main threat to human health due to its neurotoxicity and the astrocyte is known to be a common deposit site of lead in vivo. However, the detailed mechanisms related to lead exposure in the astrocytes were unclear. In order to deeply investigate this issue, we used Sprague-Dawley (SD) rats and astrocytes isolated from the hippocampus of SD rats to establish the lead-exposed animal and cell models through treating with lead acetate. The expression levels of GFAP, LC3, and p62 in the rat hippocampus were detected by immunofluorescence and Western blot after lead exposure. The effects of autophagy on lead-exposed astrocytes were studied by further autophagy inhibitor 3-methyladenine (3-MA) induction. Transmission electron microscopy was used to observe autophagosomes in astrocytes after lead acetate treatment, followed by assessing related autophagy protein markers. In addition, some inflammatory cytokines and oxidative stress markers were also evaluated after lead exposure and 3-MA administration. We found that lead exposure induced activation of astrocytes, as evidenced by increased GFAP levels and GFAP-positive staining cells in the rat hippocampus. Moreover, lead exposure induced autophagy in astrocytes, as evidenced by increased LC3II and Beclin 1 protein levels and decreased p62 expression in both the rat hippocampus and astrocytes, and it was confirmed that this autophagy was activated through blocking the downstream Akt/target of the rapamycin (mTOR) pathway in astrocytes. Furthermore, it was shown that treatment of lead acetate increased the release of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), and the accumulation of malondialdehyde (MDA) and myeloperoxidase (MPO) in astrocytes, which could be alleviated by further 3-MA induction. Therefore, we conclude that lead exposure can induce the autophagy of astrocytes via blocking the Akt/mTOR pathway, leading to accelerated release of inflammatory factors and oxidative stress indicators in astrocytes.


Assuntos
Astrócitos/metabolismo , Astrócitos/fisiologia , Autofagia/efeitos dos fármacos , Autofagia/genética , Compostos Organometálicos/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Células Cultivadas , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/citologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/genética , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
Cell ; 183(1): 143-157.e13, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877699

RESUMO

Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.


Assuntos
Infecções por Coronavirus/imunologia , Centro Germinativo/imunologia , Pneumonia Viral/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Centro Germinativo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Baço/imunologia , Baço/patologia , Fator de Necrose Tumoral alfa/metabolismo
4.
Life Sci ; 259: 118382, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898532

RESUMO

AIM: Vancomycin (VCM) is a glycopeptide antibiotic widely used to treat serious infections caused by methicillin-resistant Staphylococcus aureus and has been associated with some severe side effects such as hepatotoxicity and nephrotoxicity. However, the underlying mechanism of VCM-induced hepatotoxicity is not yet fully understood. Therefore, the current study was designed to evaluate the protective effects of zingerone (Zin) against VCM-induced hepatotoxicity in rats. MATERIALS AND METHODS: VCM was intraperitoneally administered at a dose of 200 mg/kg body weight (b.w.) for 7 days alone and in combination with the orally administered Zin (25 and 50 mg/kg b.w). KEY FINDINGS: Zin treatment significantly improved VCM-induced hepatic lipid peroxidation, glutathione depletion, reduced antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities and liver function markers (aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase). Histopathological integrity and immunohistochemical expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the VCM-induced liver tissue were ameliorated after Zin administration. In addition, Zin reversed the changes in levels and/or activities of inflammatory and apoptotic parameters such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p53, cysteine aspartate specific protease-3 (caspase-3), cysteine aspartate specific protease-8 (caspase-8), cytochrome c, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) in the VCM-induced hepatotoxicity. SIGNIFICANCE: Collectively, these results reveal probable ameliorative role of Zin against VCM-induced hepatotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Guaiacol/análogos & derivados , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vancomicina/toxicidade , Animais , Western Blotting , Ciclo-Oxigenase 2/metabolismo , Guaiacol/uso terapêutico , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
5.
Medicine (Baltimore) ; 99(33): e21667, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872031

RESUMO

BACKGROUND: This study will explore the association between tumor necrosis factor α (TNF-α) and uterine fibroids (UFs). METHODS: We will retrieve electronic databases in Cochrane Library, PUBMED, EMBASE, Web of Science, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to the present. All potential case-controlled studies investigating the association between TNF-α and UFs will be included in this study. Two researchers will independently select literature, appraise study quality, and extract outcome data. We will utilize a fixed-effects model or a random-effects model to synthesize outcome data. All data analysis will be performed by RevMan 5.3 software. RESULTS: The present study will supply high-quality synthesis and/or descriptive analysis of the recent evidence to explore the association between TNF-α and UFs. CONCLUSION: This study will exert evidence to determine whether or not TNF-α is associated with UFs. STUDY REGISTRATION NUMBER: INPLASY202070010.


Assuntos
Leiomioma/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias Uterinas/metabolismo , Biomarcadores Tumorais , Estudos de Casos e Controles , Feminino , Humanos , Revisões Sistemáticas como Assunto
6.
Korean J Parasitol ; 58(4): 393-402, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32871633

RESUMO

Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.


Assuntos
MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptor A3 de Adenosina/fisiologia , Toxoplasmose/metabolismo , Trofoblastos/metabolismo , Trofoblastos/parasitologia , Fator de Necrose Tumoral alfa/metabolismo , Células Cultivadas , Humanos
7.
PLoS One ; 15(9): e0236320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941433

RESUMO

HIV-infected older individuals may have a diminished immune response because of exhaustion/immune aging of T-cells. Therefore, we have investigated HIV-specific CD4 and CD8 T-cell responses in 100 HIV-infected patients (HIV+) who have aged on long-term antiretroviral therapy (ART) and achieved controlled viremia (mostly undetectable viral load; 92 patients with <20 to <40 HIV RNA copies/mL and 8 <60 to <100) and improved CD4 T-cell counts. We show that the median frequencies of HIV-specific CD4+ and CD8+ IFN-γ T-cells were higher in HIV+ than uninfected individuals (HIV-), including increasing levels of IFN-γproduced by CD4+ T-cells and decreasing levels by CD8+ T-cells with increasing CD4 T-cell counts in HIV+. No correlation was found between T-cell responses and varying levels of undetectable viremia. HIV-specific TNF-α made by CD8+ T-cells was higher in HIV+ than HIV-, including decreasing levels with increasing CD4 T-cell counts in HIV+. Furthermore, the CD8+ T-cell mediators, CD107a and Granzyme-B, were higher in HIV+ than HIV-, and decreased with increasing CD4 T-cell counts in HIV+. Remarkably, HIV-specific CD8 T-cells produced decreasing levels of IFN-γwith increasing age of HIV+, including decreased levels of CD107a and Granzyme-B in older HIV+. However, HIV-specific CD8+ T-cells produced increasing levels of TNF-α with increasing age of the HIV+, suggesting continued inflammation. In conclusion, HIV+ with controlled viremia on long-term ART and with higher CD4 T-cell counts showed reduced HIV-specific CD8 T-cell responses as compared to those with lower CD4 T-cell counts, and older HIV+ exhibited decreasing levels of CD8 T-cell responses with increasing age.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/sangue , Linfócitos T/imunologia , Viremia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirretrovirais/administração & dosagem , Relação CD4-CD8 , Feminino , Granzimas/genética , Granzimas/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/genética , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Viremia/tratamento farmacológico
8.
Life Sci ; 258: 118177, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738364

RESUMO

AIM: Omapatrilat is an antagonist of angiotensin-converting (ACE) and neprilysin-neuropeptidase (NEP) enzymes. The aim of our study is to show that omapatrilat may have beneficial effects as a treatment for polymicrobial sepsis. MAIN METHODS: A cecal ligation and puncture (CLP) sepsis model was used to evaluate 10 and 20 mg/kg doses of omapatrilat in mice (n = 30) fasted for 12 h. The lungs were removed 12 h after CLP, and lung levels of cytokines (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6], NF-κB), iNOS and eNOS mRNA expression, GSH and MDA levels, and ACE and NEP activities were determined. Histopathological examinations were also performed. KEY FINDINGS: Omapatrilat treatment provided a dose-dependent reduction in oxidative stress and inflammatory parameters in lung tissues. Omapatrilat administration decreased lung iNOS and eNOS mRNA levels at 20 mg/kg dose. Histopathological analysis revealed a decline in the thickening and edema areas in the alveolar septa in the Sepsis+OMA20 group. SIGNIFICANCE: Omapatrilat, a dual ACE and NEP inhibitor, protected lung tissue from sepsis damage by reducing ACE and NEP activities, by decreasing the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-6, and NF-κB), by suppressing leukocyte infiltration and edema, by restoring iNOS and eNOS levels, and by restoring SOD activity and GSH and MDA levels, thereby reducing oxidative stress.


Assuntos
Neprilisina/metabolismo , Peptidil Dipeptidase A/metabolismo , Sepse/enzimologia , Transdução de Sinais , Animais , Biomarcadores/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Pulmão/enzimologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sepse/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
Arterioscler Thromb Vasc Biol ; 40(9): 2070-2083, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32762445

RESUMO

OBJECTIVE: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar-/-/Apoe-/- mice were generated by cross-breeding of atherosclerosis-prone Apoe-/- mice and C3ar-/- mice. C3ar-/-/Apoe-/- mice and Apoe-/- mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b+ leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe-/- mice, C3ar-/-/Apoe-/- mice developed more severe atherosclerosis. In addition, C3ar-/-/Apoe-/- mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. CONCLUSIONS: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis-mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.


Assuntos
Aorta/metabolismo , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Inflamação/prevenção & controle , Macrófagos Peritoneais/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Aorta/imunologia , Aorta/patologia , Doenças da Aorta/imunologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiotaxia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , NF-kappa B/metabolismo , Fenótipo , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/deficiência , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Life Sci ; 259: 118191, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777302

RESUMO

Numerous population studies conducted worldwide indicate that the prevalence of asthma is higher in obese versus lean individuals. It has been reported that sensitized lean mice has a better recovery of lung inflammation in asthma. Extracellular matrix (ECM) plays an essential role in the structural support of the lungs regulating the airways diameter, thus preventing its collapse during expiration. ECM renewal by metalloproteinase (MMPs) enzymes is critical for pulmonary biology. There seems to be an imbalance of MMPs activity in asthma and obesity, which can impair the lung remodeling process. In this study, we characterized the pulmonary ECM of obese and lean mice, non-sensitized and sensitized with ovalbumin (OVA). Pharmacological intervention was performed by using anti-TNF-α, and MMP-8 and MMP-9 inhibitors in obese and lean sensitized mice. Activity of MMPs was assessed by gelatinase electrophorese, western blotting and zymogram in situ. Unbalance of MMP-2, MMP-8, MMP-9 and MMP-12 was detected in lung tissue of OVA-sensitized obese mice, which was accompanied by high degradation, corroborating an excessive deposition of types I and III collagen in pulmonary matrix of obese animals. Inhibitions of TNF-α and MMP-9 reduced this MMP imbalance, clearly suggesting a positive effect on pulmonary ECM. Obese and lean mice presented diverse phenotype of asthma regarding the ECM compounds and the inhibition of MMPs pathway could be a good alternative to regulate the activity in ECM lungs of asthmatic obese individuals.


Assuntos
Asma/etiologia , Asma/metabolismo , Metaloproteases/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/citologia , Matriz Extracelular/metabolismo , Inflamação/metabolismo , Pulmão/patologia , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Inibidores de Proteases/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
11.
J Appl Oral Sci ; 28: e20200033, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785523

RESUMO

Aim To evaluate the cytotoxicity, biocompatibility and mineralization capacity of BIO-C PULPO, and MTA. Methodology L929 fibroblasts were cultured and MTT assay was used to determine the material cytotoxicity on 6, 24, and 48 h. A total of 30 male rats (Wistar) aged between 4 and 6 months, weighing between 250 and 300 g were used. Polyethylene tubes containing BIO-C PULPO, MTA, and empty tubes were implanted into dorsal connective tissue. After the experimental periods (7, 15, 30, 60, and 90 days) the tubes were histologically analyzed using hematoxylin-eosin (H&E), immunolabeling of IL-1ß and TNF-α, and von Kossa staining, or without staining for polarized light analysis. The average number of inflammatory cells was quantified; the mineralization assessment was determined by the area marked in µm2 and semiquantitative immunolabeling analyses of IL-1ß and TNF-α were performed. Then, data underwent statistical analysis with a 5% significance level. Results It was observed that BIO-C PULPO and MTA presented cytocompatibility at 6, 24, and 48 similar or higher than control for all evaluated period. On periods 7 and 15 days, BIO-C PULPO was the material with the highest number of inflammatory cells (p<0.05). On periods 30, 60, and 90 days, BIO-C PULPO and MTA presented similar inflammatory reactions (p>0.05). No statistical differences were found between Control, BIO-C PULPO, and MTA for immunolabeling of IL-1ß and TNF-α in the different periods of analysis (p<0.05). Positive von Kossa staining and birefringent structures under polarized light were observed in all analyzed periods in contact with both materials, but larger mineralization area was found with BIO-C PULPO on day 90 (p<0.05). Conclusion BIO-C PULPO was biocompatible and induced mineralization similar to MTA.


Assuntos
Biomineralização , Cimentos Dentários , Interleucina-1beta/metabolismo , Materiais Restauradores do Canal Radicular , Fator de Necrose Tumoral alfa/metabolismo , Compostos de Alumínio , Animais , Materiais Biocompatíveis , Compostos de Cálcio , Combinação de Medicamentos , Inflamação , Masculino , Óxidos , Ratos , Ratos Wistar , Silicatos , Tela Subcutânea
12.
Biomed Pharmacother ; 129: 110436, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32768938

RESUMO

The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. They were randomly divided into the pure western medicine therapy group (PWM) and integrated into Chinese and Western medicine therapy group (ICW). The general strategies were given to both groups according to the national recommendations, and the ICW group was given Yidu-toxicity blocking lung decoction extraorally. A radioimmunoassay method was adopted to detect the content of IL-6, IL-8,IL-2R,TNF-α, procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in sera. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD3+, CD4+, CD8+, and the ratios of CD4+/CD8+). The white blood cell counts (WBC#), neutrophils count(N#), and lymphocyte counts (L#) were measured using a fully automatic blood rheological instrument. The t-test or Rank Sum Test and Spearman analysis were conducted to evaluate the differences. The results showed that IL-6 (P = 0.013) and TNF-α (P = 0.035) levels in the PWM group were significantly higher than those in the ICW group after treatment. Infection related indicators such as WBC#, N#, L#, hs-CRP showed no differences. The analysis showed that there was no statistical difference in the values of CD4 and CD8 between the two groups. By the end of Day 29, all patients were discharged and the final cure rate for both group were 100 %. Taken together, we conclude that Yidu-toxicity blocking lung decoction could relieve inflammation of SARS-COV-2 patients with yidu-toxicity blocking lung syndrome by eliminating inflammatory agents. CM can serve as a complementary medication to western medicine, which should be highlighted in clinical settings.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Inflamação/virologia , Interleucina-6/metabolismo , Contagem de Leucócitos , Contagem de Linfócitos , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
13.
Ecotoxicol Environ Saf ; 205: 111186, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853868

RESUMO

Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 µg/mL, characterized by increased levels of TNF-α and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion () in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction.


Assuntos
Macrófagos Alveolares/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Superóxidos/metabolismo , Poluentes Atmosféricos/toxicidade , Animais , Antioxidantes/metabolismo , Cinza de Carvão/toxicidade , Peróxido de Hidrogênio/metabolismo , Inflamação , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Camundongos , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Oxirredução , Estresse Oxidativo/imunologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
14.
PLoS One ; 15(8): e0236164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760085

RESUMO

Hyaluronan (HA) is a nonsulfated glycosaminoglycan that has been widely used for biomedical applications. Here, we have analyzed the effect of HA on the rescue of primary cells under stress as well as its potential to recover muscle atrophy and validated the developed model in vitro using primary muscle cells derived from rats. The potentials of different HAs were elucidated through comparative analyses using pharmaceutical grade a) high (HHA) and b) low molecular weight (LHA) hyaluronans, c) hybrid cooperative complexes (HCC) of HA in three experimental set-ups. The cells were characterized based on the expression of myogenin, a muscle-specific biomarker, and the proliferation was analyzed using Time-Lapse Video Microscopy (TLVM). Cell viability in response to H2O2 challenge was evaluated by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression of the superoxide dismutase enzyme (SOD-2) was assessed by western blotting. Additionally, in order to establish an in vitro model of atrophy, muscle cells were treated with tumor necrosis factor-alpha (TNF-α), along with hyaluronans. The expression of Atrogin, MuRF-1, nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB), and Forkhead-box-(Fox)-O-3 (FoxO3a) was evaluated by western blotting to elucidate the molecular mechanism of atrophy. The results showed that HCC and HHA increased cell proliferation by 1.15 and 2.3 folds in comparison to un-treated cells (control), respectively. Moreover, both pre- and post-treatments of HAs restored the cell viability, and the SOD-2 expression was found to be reduced by 1.5 fold in HA-treated cells as compared to the stressed condition. Specifically in atrophic stressed cells, HCC revealed a noteworthy beneficial effect on the myogenic biomarkers indicating that it could be used as a promising platform for tissue regeneration with specific attention to muscle cell protection against stressful agents.


Assuntos
Ácido Hialurônico/farmacologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/terapia , Medicina Regenerativa/métodos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/metabolismo , Géis , Humanos , Ácido Hialurônico/química , Peróxido de Hidrogênio/toxicidade , Microscopia Intravital , Peso Molecular , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/patologia , Miogenina/análise , Miogenina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Cultura Primária de Células , Ratos , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Imagem com Lapso de Tempo , Fator de Necrose Tumoral alfa/metabolismo
15.
PLoS One ; 15(8): e0236727, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750068

RESUMO

Low-power laser irradiation (LPLI) is clinically used to modulate inflammation, proliferation and apoptosis. However, its molecular mechanisms are still not fully understood. This study aimed to describe the effects of LPLI upon inflammatory, apoptotic and proliferation markers in submandibular salivary glands (SMGs) in an experimental model of chronic disorder, 24h after one time irradiation. Diabetes was induced in rats by the injection of streptozotocin. After 29 days, these animals were treated with LPLI in the SMG area, and euthanized 24h after this irradiation. Treatment with LPLI significantly decreased diabetes-induced high mobility group box 1 (HMGB1) and tumor necrosis factor alpha (TNF-α) expression, while enhancing the activation of the transcriptional factor cAMP response element binding (CREB) protein. LPLI also reduced the expression of bax, a mitochondrial apoptotic marker, favoring the cell survival. These findings suggest that LPLI can hamper the state of chronic inflammation and favor homeostasis in diabetic rats SMGs.


Assuntos
Diabetes Mellitus Experimental/radioterapia , Terapia com Luz de Baixa Intensidade , Transdução de Sinais/efeitos da radiação , Glândula Submandibular/efeitos da radiação , Animais , Apoptose , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosforilação , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
16.
J Oleo Sci ; 69(8): 929-939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759551

RESUMO

Glucosylceramide (GlcCer), a major sphingolipid in plants and fungi, is known to have food functions, such as preventing intestinal impairment and enhancing the moisture content of skin. This study investigated the influence of fermentation on the composition and function of lipophilic components containing GlcCer in plant-based foods; we compared the effects of ethanol extracts from sake rice (SR) and sake lees (SL) on colon impairment in mice. GlcCer and ceramide (Cer) levels in SL were much higher than those in SR, and GlcCer in SL contained 9-methyl-trans-4,trans-8-sphingadienine as a fungi-specific sphingoid base. 1,2-dimethylhydrazine (DMH) treatment markedly increased the formation of aberrant crypt foci (ACF) and the levels of TNF-α and lipid oxidation in mice colons. However, dietary SR or SL significantly suppressed these DMH-induced changes, and SR demonstrated stronger effects than SL. In addition, dietary SR or SL suppressed the expression of apoptotic and anti-apoptotic proteins induced by DMH treatment. This study suggests that SR or SL intake could reduce colon ACF formation via the suppression of inflammation and oxidation-induced cell cycle disturbances. When compared to SR, the weaked effects of SL rich in GlcCer may be the result of the changes in sphingolipid composition (sphingoid base and Cer) and differences in the concentration of other bioactive compounds produced or digested during fermentation.


Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Neoplasias do Colo/prevenção & controle , Glucosilceramidas/análise , Glucosilceramidas/farmacologia , Oryza/química , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Vinho/análise , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Administração Oral , Animais , Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Etanol , Feminino , Fermentação , Glucosilceramidas/administração & dosagem , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
17.
PLoS Negl Trop Dis ; 14(8): e0008495, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764765

RESUMO

Melioidosis is an often-severe tropical infection caused by Burkholderia pseudomallei (Bp) with high associated morbidity and mortality. Burkholderia thailandensis (Bt) is a closely related surrogate that does not require BSL-3 conditions for study. Lactoferrin is an iron-binding glycoprotein that can modulate the innate inflammatory response. Here we investigated the impact of lactoferrin on the host immune response in melioidosis. Lactoferrin concentrations were measured in plasma from patients with melioidosis and following ex vivo stimulation of blood from healthy individuals. Bt growth was quantified in liquid media in the presence of purified and recombinant human lactoferrin. Differentiated THP-1 cells and human blood monocytes were infected with Bt in the presence of purified and recombinant human lactoferrin, and bacterial intracellular replication and cytokine responses (tumor necrosis factor-α (TNF-α), interleukin-1ß and interferon-γ) were measured. In a cohort of 49 melioidosis patients, non-survivors to 28 days had significantly higher plasma lactoferrin concentrations compared to survivors (median (interquartile range (IQR)): 326 ng/ml (230-748) vs 144 ng/ml (99-277), p<0.001). In blood stimulated with heat-killed Bp, plasma lactoferrin concentration significantly increased compared to unstimulated blood (median (IQR): 424 ng/ml (349-479) vs 130 ng/ml (91-214), respectively; p<0.001). Neither purified nor recombinant human lactoferrin impaired growth of Bt in media. Lactoferrin significantly increased TNF-α production by differentiated THP-1 cells and blood monocytes after Bt infection. This phenotype was largely abrogated when Toll-like receptor 4 (TLR4) was blocked with a monoclonal antibody. In sum, lactoferrin is produced by blood cells after exposure to Bp and lactoferrin concentrations are higher in 28-day survivors in melioidosis. Lactoferrin induces proinflammatory cytokine production after Bt infection that may be TLR4 dependent.


Assuntos
Infecções por Burkholderia/metabolismo , Infecções por Burkholderia/microbiologia , Burkholderia , Lactoferrina/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Burkholderia pseudomallei , Células Cultivadas , Humanos , Melioidose/metabolismo , Monócitos , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética
18.
J Oleo Sci ; 69(9): 1139-1143, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788524

RESUMO

We compared the cytotoxic effects and tumor necrosis factor-α (TNF-α) production induced by 13 trans-octadecenoic acid positional isomers (trans-4-C18:1 to trans-16-C18:1) in RAW264.7 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and enzyme-linked immunosorbent assay, respectively. No significant differences were observed in the cytotoxic effects among the 13 trans-C18:1 positional isomers and control on RAW264.7 cells. TNF-α production significantly decreased by treatment of trans-4-C18:1 as compared to control, but no significant differences in TNF-α production were observed among other trans-C18:1 positional isomers and control. These results suggest that the double bond position in trans-C18:1 may affect TNF-α production in cells.


Assuntos
Células RAW 264.7/metabolismo , Ácidos Esteáricos/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Animais , Isomerismo , Camundongos , Ácidos Esteáricos/química , Relação Estrutura-Atividade
19.
Yonsei Med J ; 61(8): 660-669, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734729

RESUMO

PURPOSE: Neonatal hypoxic ischemic encephalopathy (HIE) is an essential factor underlying neonatal death and disability. This study sought to explore the role of miR-146b-5p in regulating neonatal HIE. MATERIALS AND METHODS: In vitro and in vivo HIE models were established in PC12 cells and 10-day neonatal Sprague Dawley rats, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess miR-146b-5p expression and inflammatory factors [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] in brain lesions and PC12 cells, while enzyme-linked immunosorbent assay was employed to detect the expression of oxidative stress factors (SOD and GSH-Px). Gain- and loss-assays of miR-146b-5p were conducted to verify its role in modulating the viability and apoptosis of PC12 cells under oxygen-glucose deprivation (OGD) treatment. Expression of TLR4, IRAK1, TRAF6, TAK1, and NF-κB were examined by qRT-PCR and/or Western blot. Dual luciferase activity assay was conducted to identify relationships between miR-146b-5p and IRAK1. RESULTS: In the HIE models, significant oxidative stress and inflammatory responses emerged upon upregulation of TLR4/IRAK1/TRAF6/TAK1/NF-κB signaling. Overexpression of miR-146b-5p greatly inhibited OGD-induced PC12 cell injury, inflammatory responses, and oxidative stress. Inhibiting miR-146b-5p, however, had the opposite effects. IRAK1 was found to be a target of miR-146b-5p, and miR-146b-5p overexpression suppressed the activation of IRAK1/TRAF6/TAK1/NF-κB signaling. CONCLUSION: This study demonstrated that miR-146b-5p overexpression alleviates HIE-induced neuron injury by inhibiting the IRAK1/TRAF6/TAK1/NF-κB pathway.


Assuntos
Hipóxia-Isquemia Encefálica/genética , Quinases Associadas a Receptores de Interleucina-1/metabolismo , MAP Quinase Quinase Quinases/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/genética , Sequência de Bases , Modelos Animais de Doenças , Regulação para Baixo/genética , Glucose/deficiência , Inflamação/patologia , MicroRNAs/genética , Estresse Oxidativo , Oxigênio , Células PC12 , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
20.
Life Sci ; 258: 118136, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726662

RESUMO

The endothelium is a critical regulator of vascular homeostasis, controlling vascular tone and permeability as well as interactions of leukocytes and platelets with blood vessel walls. Consequently, endothelial dysfunction featuring inflammation and reduced vasodilation are considered central to cardiovascular disease (CVD) pathogenesis and have become a therapeutic area of focus. Type II endothelial cell (EC) activation by stress-related stimuli such as tumor necrosis factor-α (TNF-α) initiates the nuclear factor-κB (NF-κB) signaling pathway, a master regulator of inflammatory responses. Because dysregulated NF-κB signaling has been tightly linked to several CVDs, EC-specific inhibition of NF-κB represents an attractive pharmacological strategy. As accumulating evidence highlights the clinical benefits of tea catechin for multiple diseases including CVDs, we sought to determine whether the tea catechin epigallocatechin gallate (EGCG) that displays antioxidative, anti-inflammatory, hypolipidemic, anti-thrombogenic, and anti-hypertensive properties offers protection against CVDs by suppressing the canonical NF-κB pathway. Our findings indicate that EGCG downregulates multiple components of the TNF-α-induced NF-κB signaling pathway and thereby reduces the consequent increase in inflammatory gene transcription and protein expression. Furthermore, EGCG blocked type II EC activation, evidenced by diminished EC leakage and monocyte adhesion in EGCG-treated cells. In summary, our study advances knowledge of EGCG's anti-inflammatory effects on the NF-κB pathway and hence its benefits on endothelial health, supporting its therapeutic potential for CVDs.


Assuntos
Catequina/análogos & derivados , Vasos Coronários/patologia , Células Endoteliais/patologia , Inflamação/tratamento farmacológico , Catequina/farmacologia , Catequina/uso terapêutico , Adesão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/patologia , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA