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1.
Gene ; 723: 143986, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31323309

RESUMO

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Accumulating evidence shows that microRNAs play important roles in diabetic kidney. However, the potential role of MicroRNA-544 (miR-544) in DN remains unclear. In this study, we explored the role of miR-544 on inflammation and fibrosis in diabetic kidney using db/db mice. Renal expression of miR-544 was decreased in mice, companied by increased the expression of FASN. The dual luciferase assay confirmed FASN as a direct target of miR-544. Over-expression of miR-544 significantly ameliorated renal injury, mesangial matrix and renal fibrosis. In addition, over-expression of miR-544 significantly attenuated inflammatory cells infiltration and IL-1, IL-6, TNF- and iNOS production in DN. Furthermore, miR-544 over-expression inhibited the activation of NF-kB signal pathway in DN. In conclusion, our finding demonstrated that miR-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN, suggesting that miR-544 might have therapeutic potential for the treatment of DN.


Assuntos
Citocinas/metabolismo , Nefropatias Diabéticas/genética , Ácido Graxo Sintase Tipo I/genética , MicroRNAs/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Regiões 3' não Traduzidas , Animais , Nefropatias Diabéticas/imunologia , Modelos Animais de Doenças , Regulação para Baixo , Células HEK293 , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Camundongos , NF-kappa B/metabolismo , Receptores para Leptina/genética , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
2.
Einstein (Sao Paulo) ; 18: eAO4784, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31553356

RESUMO

OBJECTIVE: To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. METHODS: Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. RESULTS: Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. CONCLUSION: Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.


Assuntos
Adiposidade/fisiologia , Hipertrofia/fisiopatologia , Inflamação/fisiopatologia , Resistência à Insulina/fisiologia , Exercícios de Alongamento Muscular/métodos , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Tecido Adiposo Branco/fisiopatologia , Animais , Glicemia/análise , Peso Corporal/fisiologia , Dieta Hiperlipídica , Ensaio de Imunoadsorção Enzimática , Masculino , Camundongos , Camundongos Obesos , Reprodutibilidade dos Testes , Treinamento de Resistência/métodos , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise
3.
Biomed Khim ; 65(5): 432-436, 2019 Aug.
Artigo em Russo | MEDLINE | ID: mdl-31666417

RESUMO

Concentrations of eight different cytokines and the level of expression of CD86 and CD163 macrophages were studied in peritoneal fluid in women with endometriosis. It was found that the concentration of both inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) as well as the level of macrophage expression of the proinflammatory marker CD86 and anti-inflammatory marker CD163 increased in women with mild external genital endometriosis (1-2 stage), and did not differ from the control group in women with severe endometriosis (3-4 stage). The content of IL-2, IL-10, CM-CSF and IFN-γ in the peritoneal fluid of women with endometriosis did not differ significantly from the control group. The results of the study indicate that the development of external genital endometriosis may be based on insufficient both inflammatory and anti-inflammatory activity of macrophages in the peritoneal fluid.


Assuntos
Líquido Ascítico , Citocinas/imunologia , Endometriose/patologia , Macrófagos/metabolismo , Endometriose/imunologia , Feminino , Genitália/patologia , Humanos , Interleucina-4 , Interleucina-6 , Interleucina-8 , Fator de Necrose Tumoral alfa
4.
Zhongguo Zhen Jiu ; 39(11): 1181-4, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724354

RESUMO

OBJECTIVE: To explore the clinical effect of acupuncture and the potential effect mechanism in patients with premature ovarian failure. METHODS: A total of 104 patients with premature ovarian failure were randomized into an acupuncture group and a western medication group, 52 cases in each one. In the western medication group, the conjugated estrogens tablets were prescribed for oral administration, 0.625 mg each time, once a day, consecutively for 21 days. On the 16th day of medication with conjugated estrogens tablets, the oral administration of medroxyprogesterone acetate tablets were supplemented, 10 mg each time, once a day, consecutively for 5 days, and then, these two kinds of western medication were discontinued for 1 week. A total of 3 cycles were required in treatment with 28 days as an artificial cycle. In the acupuncture group, acupuncture was applied. Two groups of acupoints were selected. The first group of acupoints were stimulated before ovulation and the acupoints were Guanyuan (CV 4), Guilai (ST 29), Taichong (LR 3), Taixi (KI 3), Xuehai (SP 10), Sanyinjiao (SP 6), Zigong (EX-CA 1), Yinlingquan (SP 9), Zusanli (ST 36), Shuidao (ST 28), Dahe (KI 12) and Tianshu (ST 25). The second group of acupoints were stimulated after ovulation and the acupoints included Ciliao (BL 32), Shiqizhui (EX-B 8), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Pishu (BL 20). The therapeutic effect was observed and compared in the patients between the two groups, as well as the expressions of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and the levels of serum luteinizing hormone (LH), follicule stimulating hormone (FSH) and estradiol (E2) before and after treatment. RESULTS: The total effective rate was 90.4% (47/52) in the acupuncture group, higher than 67.3% (35/62) in the western medication group (P<0.05). After treatment, the expressions of IFN-γ and TNF-α in the acupuncture group were obviously lower than the western medication group (P<0.05). Except for serum LH after treatment, at the end of treatment and in 30 days and 90 days after treatment, the levels of serum E2 in the acupuncture group were higher obviously than the western medication group and the levels of serum LH and FSH were lower obviously than the western medication group (all P<0.05). CONCLUSION: Acupuncture promotes the regular menstruation, effectively regulates the levels of serum LH, FSH and E2 and improves the pituitary gland and the ovary endocrine in the patients with premature ovarian failure. Such effect may be related to the the improvements in the expressions of IFN-γ and TNF-α, the inhibition of the apoptosis of ovarian granulosa cells, the recovery of ovarian function and the enhancement of reserve capacity.


Assuntos
Terapia por Acupuntura , Interferon gama/sangue , Insuficiência Ovariana Primária , Fator de Necrose Tumoral alfa/sangue , Pontos de Acupuntura , Feminino , Humanos , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/terapia
5.
Cell Physiol Biochem ; 53(5): 865-886, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724838

RESUMO

BACKGROUND/AIMS: Heart failure is characterized by chronic low-grade vascular inflammation, which in itself can lead to endothelial dysfunction. Clinical trials showed reductions in heart failure-related hospitalizations of type 2 diabetic patients using sodium glucose co-transporter 2 inhibitors (SGLT2i's). Whether and how SGLT2i's directly affect the endothelium under inflammatory conditions is not completely understood. The aim of the study was to investigate whether the SGLT2i Empagliflozin (EMPA) and Dapagliflozin (DAPA) reduce tumor necrosis factor α (TNFα) induced endothelial inflammation in vitro. METHODS: Human coronary arterial endothelial cells (HCAECs) and human umbilical vein endothelial cells (HUVECs) were (pre-)incubated with 1 µM EMPA or DAPA and subsequently exposed to 10 ng/ml TNFα. ROS and NO were measured using live cell imaging. Target proteins were either determined by infrared western blotting or fluorescence activated cell sorting (FACS). The connection between Cav-1 and eNOS was determined by co-immunoprecipitation. RESULTS: Nitric oxide (NO) bioavailability was reduced by TNFα and both EMPA and DAPA restored NO levels in TNFα-stimulated HCAECs. Intracellular ROS was increased by TNFα, and this increase was completely abolished by EMPA and DAPA in HCAECs by means of live cell imaging. eNOS signaling was significantly disturbed after 24 h when cells were exposed to TNFα for 24h, yet the presence of both SGLT2is did not prevent this disruption. TNFα-induced enhanced permeability at t=24h was unaffected in HUVECs by EMPA. Similarly, adhesion molecule expression (VCAM-1 and ICAM-1) was elevated after 4h TNFα (1.5-5.5 fold increase of VCAM-1 and 4-12 fold increase of ICAM-1) but were unaffected by EMPA and DAPA in both cell types. Although we detected expression of SGLT2 protein levels, the fact that we could not silence this expression by means of siRNA and the mRNA levels of SGLT2 were not detectable in HCAECs, suggests aspecificity or our SGLT2 antibody and absence of SGLT2 in our cells. CONCLUSION: These data suggest that EMPA and DAPA rather restore NO bioavailability by inhibiting ROS generation than by affecting eNOS expression or signaling, barrier function and adhesion molecules expression in TNFα-induced endothelial cells. Furthermore, the observed effects cannot be ascribed to the inhibition of SGLT2 in endothelial cells.


Assuntos
Compostos Benzidrílicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Glucosídeos/farmacologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Vasos Coronários/citologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Permeabilidade/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/genética , Transportador 2 de Glucose-Sódio/metabolismo , Molécula 1 de Adesão de Célula Vascular
6.
Int J Oral Sci ; 11(3): 30, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31685798

RESUMO

Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in the periodontal region. Although dysbiosis of the local microbial community initiates local inflammation, over-activation of the host immune response directly activates osteoclastic activity and alveolar bone loss. Many studies have reported on the cytokine network involved in periodontitis and its crucial and pleiotropic effect on the recruitment of specific immunocytes, control of pathobionts and induction or suppression of osteoclastic activity. Nonetheless, particularities in the stimulation of pathogens in the oral cavity that lead to the specific and complex periodontal cytokine network are far from clarified. Thus, in this review, we begin with an up-to-date aetiological hypothesis of periodontal disease and summarize the roles of cytokines in the host immune response. In addition, we also summarize the latest cytokine-related therapeutic measures for periodontal disease.


Assuntos
Citocinas/metabolismo , Inflamação , Periodontite/imunologia , Periodontite/microbiologia , Perda do Osso Alveolar/etiologia , Citocinas/fisiologia , Humanos , Doenças Periodontais , Fator de Necrose Tumoral alfa/fisiologia
7.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 293-296, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701708

RESUMO

OBJECTIVE: To investigate the effects of vitamin E on the respiratory function impairment in rats with chronic obstructive pulmonary disease (COPD) after exposed to high temperature and PM2.5. METHODS: Fifty-four 7-week-old SPF male Wistar rats were randomly divided into 9 experimental groups (n=6). The rat COPD model was established by lipopolysaccharide (LPS) and smoke exposure. After modeled, the rats were tracheal instilled with PM2.5 (0 mg/ml, 3.2 mg/ml) and intraperitoneally injected with vitamin E at the dose of 40 mg/kg (20 mg/ml). Part of rats (high temperature groups) were then exposed to high temperature (40℃), once (8 h) a day for three consecutive days. After the last exposure, the lung function of rats was detected. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were detected by corresponding ELISA kits. RESULTS: Compared with the control group, exposure of high temperature and PM2.5 could inhibit the lung function of COPD rats significantly (P<0.05); the level of MCP-1 was increased significantly in PM2.5-exposure groups (P<0.05); iNOS was increased significantly in the groups of high temperature (P<0.05). Compared with the single-PM2.5 exposure groups, TNF-α in lung was decreased in the normal temperature health group and high temperature COPD group (P<0.05) after treated with vitamin E; MCP-1 was decreased in all vitamin E-treated groups (P<0.05); the decreased iNOS only appeared in the group of high temperature with vitamin E treatment. CONCLUSION: High temperature and PM2.5 could aggravate the inflammation of COPD rats. As an antioxidant, vitamin E may protect the lung from the damage effects.


Assuntos
Temperatura Alta/efeitos adversos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Vitamina E/farmacologia , Animais , Quimiocina CCL2/metabolismo , Pulmão/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
8.
Medicine (Baltimore) ; 98(44): e17768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689839

RESUMO

Relapsing polychondritis (RP) is a rare immune-mediated disease affecting cartilaginous structures. Respiratory tract manifestations are frequent and constitute a major cause of morbidity and mortality. The present review of the literature was designed to assess the efficacy of tumor necrosis factor alpha (TNF-α) inhibitors in respiratory tract involvement of RP.A MEDLINE literature search was performed from January 2000 to December 2016 to identify all studies and case reports of anti-TNF-α therapy in RP. Articles published in English or French concerning patients with respiratory tract involvement were eligible. Two authors (JB, FL) independently reviewed and extracted data concerning each patient and 2 personal cases were added. Treatment efficacy was assessed according to systemic and/or respiratory criteria.A total of 28 patients (mean age: 41.6 years; 16 females/12 males) were included in the final analysis. Anti-TNF-α therapy was associated with improved health status and respiratory symptoms in 67.8% and 60.1% of cases, respectively.These results suggest that TNF-α inhibitors could be considered for the treatment of respiratory tract involvement of RP.


Assuntos
Antirreumáticos/uso terapêutico , Policondrite Recidivante/tratamento farmacológico , Doenças Respiratórias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Policondrite Recidivante/complicações , Sistema Respiratório/efeitos dos fármacos , Doenças Respiratórias/etiologia , Resultado do Tratamento
9.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 728-731, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726501

RESUMO

Objective: To observe the lung injury of male rats induced by sub-chronic exposure to crotonaldehyde, and to explore the possible mechanism of injury. Methods: Forty SPF male Wistar rats were randomly divided into control group and 3 groups in each group, and each group received 0.0, 2.5, 4.5, 8.5 mg/kg body weight crotonaldehyde solution for continuous intragastric administration. 120 d, once a day. After the end of the exposure, the body weight of the rats was measured, and the lung tissues were quickly separated after cervical dislocation. The organ coefficients were calculated and histopathological examination was performed to determine malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione. Peroxidase (GSH-Px) content; ELISA was used to measure interleukin (IL) -6, IL-1ß, and tumor necrosis factor (TNF) -α in lung tissues. Results: Compared with the control group, the weight gain of the rats in the 4.5 and 8.5 mg/kg exposure groups was small, and the lung weight and organ coefficient of the exposed group decreased, the difference was statistically significant (P<0.05). In the exposed group, the lung tissue structure was disordered, the alveolar wall was thickened, and inflammatory cell infiltration was observed. Compared with the control group, the MDA activity in the serum of the rats in the 4.5 mg/kg and 8.5 mg/kg groups increased, and the SOD and GSH-Px activities decreased, the difference was statistically significant (P<0.05). TNF-α levels in the lung tissues of rats exposed to 4.5 mg/kg and 8.5 mg/kg, and levels of (IL) -6 and IL-1ß in the lungs of rats in the 2.5, 4.5, and 8.5 mg/kg groups. Significantly increased, the difference was statistically significant (P<0.05) . Conclusion: Crotonaldehyde may induce inflammatory and oxidative stress damage in rats by up-regulating the expression of inflammatory factors in lung tissue and changing the oxidative balance.


Assuntos
Inflamação , Lesão Pulmonar/induzido quimicamente , Estresse Oxidativo , Aldeídos , Animais , Glutationa/análise , Pulmão , Masculino , Malondialdeído/análise , Peroxidase/análise , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/análise , Fator de Necrose Tumoral alfa/análise
10.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 732-736, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726502

RESUMO

Objective: To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) . Methods: The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model. Results: The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells. Conclusion: Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.


Assuntos
Lesão Pulmonar Aguda/patologia , Células Endoteliais/citologia , Histonas/sangue , Síndrome do Desconforto Respiratório do Adulto/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Células Endoteliais/patologia , Ácido Clorídrico , Inflamação , Pulmão , Camundongos , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Trombomodulina/sangue , Fator de Necrose Tumoral alfa/sangue
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1110-1115, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753094

RESUMO

OBJECTIVE: To study the effect of PR-957 on the formation of A1 reactive astrocytes. METHODS: The cerebral cortices of 1-day-old female rats were obtained and cultured for primary astrocytes. These cells were divided into 3 groups: control, lipopolysaccharide (LPS), and LPS+PR-957. The LPS group was treated with LPS (at a concentration of 5 µmol/L) for 48 hours; the LPS+PR-957 group was treated with PR-957 (at a final concentration of 200 nmol/L) for 1 hour and then LPS for 48 hours. Enzyme-linked immunosorbent assay was used to determine the expression of complement 3 (C3, a marker for A1 reactive astrocytes) and tumor necrosis factor alpha (TNF-α). Quantitative real-time PCR was used to determine the relative mRNA expression of glypican-6 (GPC6), SPARC-like 1 (SPARCL1), and lipocalin-2 (LCN2). All the above experiments were repeated three times independently. RESULTS: C3 expression was almost not observed in the control group, but was observed in both the LPS group and the LPS+PR-957 group, with significantly lower expression observed in the LPS+PR-957 group (P<0.05). The expression of TNF-α was consistent with that of C3. Compared with the control group, the LPS and the PS+PR-957 groups had significantly reduced mRNA expression levels of GPC6 and SPARCL1 but significantly increased mRNA expression level of LCN2 (P<0.001). Compared with the LPS group, the LPS+PR-957 group had significantly increased mRNA expression levels of GPC6 and SPARCL1 but significantly reduced mRNA expression level of LCN2 (P<0.001). CONCLUSIONS: LPS can induce the transformation from astrocytes to A1 reactive astrocytes, and PR-957 can inhibit the formation of LPS-induced A1 reactive astrocytes.


Assuntos
Astrócitos , Animais , Feminino , Lipopolissacarídeos , Oligopeptídeos , Ratos , Fator de Necrose Tumoral alfa
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1131-1137, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753097

RESUMO

OBJECTIVE: To establish a congenital chloride diarrhea (CCD)-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model, and to investigate its biological function. METHODS: The sequence of the SLC26A3 gene in GenBank was used to design the upstream and downstream single-guide RNA (sgRNA) that could specifically recognize the 392 locus of the SLC26A3 gene, and the sgRNA was mixed with the pSpCas9-puro vector after enzyme digestion to construct an eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3). Caco-2 cells were transfected with the recombinant plasmid and synthesized single-stranded DNA oligonucleotides (ssODNs), and Taqman genotyping assay and Sanger sequencing were used to identify the expression of SLC26A3 c.392C>G (p.P131R) in Caco-2 cells. Wild-type Caco-2 cells were selected as normal control group and the Caco-2 cells with successful expression of SLC26A3 c.392C>G (p.P131R) was selected as P131R group. Both groups were treated with 100 ng/mL tumor necrosis factor-α (TNF-α), and then the normal control group was named as TNF-α group, and the P131R group was named as TNF-α+P131R group. Electric cell-substrate impedance sensing (ECIS) assay was used to evaluate the change in the monolayer barrier function of intestinal epithelial cells in the above four groups, and Western blot was used to measure the change in the expression of SLC26A3 protein in the normal control group and the P131R group. RESULTS: The eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3) was successfully constructed. Both Taqman genotyping assay and Sanger sequencing confirmed the successful establishment of the Caco-2 cell model of SLC26A3 c.392C>G (p.P131R) expression. ECIS assay showed that compared with the normal control group, the P131R group had a significant increase in the monolayer permeability of intestinal epithelial cells (P<0.05), and at the same time, the P131R group had a significantly greater increase in cell membrane permeability after the induction with 100 ng/mL TNF-α (P<0.05). Western blot showed that compared with the normal control group, the P131R group had a significant reduction in the expression of SLC26A3 protein (P=0.001). CONCLUSIONS: SLC26A3 c.392C>G (p.P131R) can reduce the expression of SLC26A3 protein, increase the monolayer permeability of intestinal epithelial cells, and thus lead to diarrhea.


Assuntos
Antiportadores de Cloreto-Bicarbonato/genética , Diarreia/congênito , Erros Inatos do Metabolismo , Transportadores de Sulfato/genética , Células CACO-2 , Diarreia/genética , Humanos , Mucosa Intestinal , Erros Inatos do Metabolismo/genética , Polimorfismo de Nucleotídeo Único , Junções Íntimas , Fator de Necrose Tumoral alfa
13.
Rev Med Suisse ; 15(671): 2105-2108, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742942

RESUMO

Screening for latent tuberculosis infection (LTI) is recommended in immunosuppressed patients due to an increased risk of progression from LTI to active tuberculosis. Screening involves indirect immunological tests such as the tuberculin skin test (TST) and the interferon-y release assays (IGRAs). IGRAs seem to show superior performance compared to TST in screening for LTI. However, their use and interpretation in immunosuppressed patients is questionable, particularly because of an increased number of false negative or indeterminate results and a low agreement between tests. Presently, there are no swiss national recommendations for their use in immunosuppressed -patients, except for candidates to anti-TNF treatment.


Assuntos
Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/microbiologia , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Humanos , Testes de Liberação de Interferon-gama , Sensibilidade e Especificidade , Teste Tuberculínico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 800-805, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750821

RESUMO

Objective To investigate the role and mechanism of histone deacetylase 3 (HDAC3) in alcohol-induced inflammation and permeability of intestinal epithelial cells. Methods To select the proper concentration of alcohol, differentiated Caco-2 cells were treated with different concentrations (10, 25, 50, 100 and 200 mmol/L) of alcohol, and then cell viability was assayed by MTT assay; the mRNA and protein levels of HDAC3 were analyzed by real-time PCR and Western blot analysis. Differentiated Caco-2 cells were divided into three groups: control group, alcohol group (treatment with 50 mmol/L alcohol for 60 minutes), and alcohol combined with HDAC3 inhibitor group (pretreatment with 2 µmol/L RGFP966 1 hour before alcohol). ELISA was performed to detect tumor necrosis factor α (TNF-α) level in cell supernatant. Transepithelial electrical resistance (TER) was measured using a resistance meter. Western blot analysis was used to determine the protein levels relevant to tight junction (occludin and claudin-1) and NF-κB activation (IκB and phosphorylated NF-κBp65). Results Alcohol at 10, 25 and 50 mmol/L did not affect cell viability. The mRNA and protein expression levels of HDAC3 increased in a dose-dependent manner after alcohol treatment at these concentration s. Compared with the control group, TNF-α and phosphorylated NF-κBp65 levels increased, whereas TER and protein levels of occludin, claudin-1 and IκB decreased in the alcohol group. Compared with the alcohol group, TNF-α and phosphorylated NF-κBp65 levels were reduced, while TER and protein levels of occludin, claudin-1 and IκB were elevated in the alcohol combined with HDAC3 inhibitor group. Conclusion HDAC3 inhibition can attenuate alcohol-induced inflammation and permeability of intestinal epithelial cells, which may be related to the inactivation of NF-κB.


Assuntos
Etanol/efeitos adversos , Inibidores de Histona Desacetilases/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Fator de Transcrição RelA/antagonistas & inibidores , Células CACO-2 , Claudina-1/metabolismo , Histona Desacetilases , Humanos , Proteínas I-kappa B/metabolismo , Inflamação , Mucosa Intestinal/patologia , Ocludina/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa
15.
Braz Oral Res ; 33: e059, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31664357

RESUMO

We recently demonstrated that a co-culture system of human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs) could enhance angiogenesis ability in vitro. However, whether tumor necrosis factor α (TNF-α) could promote blood vessel formation during pulp regeneration remained unknown. The aim of this study was to investigate the effects of TNF-α on the formation of endothelial tubules and vascular networks in a co-culture system of hDPSCs and HUVECs. hDPSCs were co-cultured with HUVECs at a ratio of 1:5. The Matrigel assay was performed to detect the total tubule branching lengths and numbers of branches, and the Cell-Counting Kit 8 assay was performed to examine the effect of TNF-α on cell proliferation. Real-time polymerase chain reactions and western blot were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression. The Matrigel assay showed significantly greater total branching lengths and numbers of branches formed in the experimental groups treated with different concentrations of TNF-α compared with the control group. The decomposition times of the tubule structures were also significantly prolonged (P < 0.05). Treatment with 50 ng/ml TNF-α did not significantly change the proliferation of co-cultured cells, but it significantly increased the VEGF mRNA and protein expression levels (p < 0.05). In addition, the migration abilities of HUVECs and hDPSCs increased after co-culture with TNF-α (p < 0.05). TNF-α enhanced angiogenic ability in vitro in the co-culture system of hDPSCs and HUVECs.


Assuntos
Indutores da Angiogênese/farmacologia , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Adolescente , Adulto , Western Blotting , Contagem de Células , Ensaios de Migração Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Colágeno , Polpa Dentária/fisiologia , Combinação de Medicamentos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Laminina , Neovascularização Fisiológica/fisiologia , Proteoglicanas , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Adulto Jovem
16.
Zhen Ci Yan Jiu ; 44(10): 703-8, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31657158

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on incisional pain and expression of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and interleukin-4 (IL-4) of cervical dorsal part of spinal cord in rats with incisional neck pain, so as to explore its analgesic mechanisms. METHODS: Eighty-four male SD rats were randomly divided into normal control, model, EA-Futu(LI18) and EA-Zusanli(ST36)-Yanglingquan(GB34, EA-ST36-GB34) groups (n=21 in each group). The incisional neck pain model was established by making a longitudinal incision along the bilateral cervical thyroid regions and repeated mechanical separation stimulation. For rats of the EA groups, EA (2 Hz/100 Hz, 1 mA) was applied to bilateral LI18 or ST36-GB34 for 30 min/ time during the surgery, and 20 and 44 h after surgery, respectively. The thermal pain threshold (TPT) of the incisional region was detected. The immunoactivity of TNF-α and IL-10 of the dorsal portion of the cervical spinal cord (C2-C5) was detected by immunofluorescence, and the expression of TNF-α, IL-10, IL-4 and IL-4 receptor (IL-4R) mRNAs was determined by quantitative real-time PCR. RESULTS: Compared with the normal group, the TPT of the incisional area was significantly decreased at 4, 24 and 48 h after neck-incision (P<0.05), the levels of TNF-α mRNA, IL-10 mRNA and TNF-α IL-10 immunoactivity at 24 h were remarkably increased (P<0.05), and the expression of IL-4R mRNA was considerably decreased at 24 h in the model group (P<0.05). Following EA intervention, the TPT, and expression levels of IL-4 mRNA and IL-4R mRNA were significantly increased at 24 h after surgery in the EA-LI18 group relevant to the model group (P<0.05), while the expression level of TNF-α(coexpressed with microgliacytes) in the EA-LI18 group, and TNF-α mRNA expression at 24 h in both EA-LI18 and EA-ST36-GB34 groups, as well as the expression of IL-10 and IL-10 mRNA at 24 h in both EA-LI18 and EA-ST36-GB34 groups were significantly decreased (P<0.05). The effect of EA LI18 was significantly superior to that of EA ST36-GB34 in up-regulating TPT and expression of IL-4 mRNA and IL-4R mRNA at 24 h (P<0.05). CONCLUSION: EA of LI18 has an analgesic effect in incisional neck pain rats, which may be related to its effect in down-regulating the expression of TNF-α, IL-10 and promoting IL-4 /IL-4R signaling in dorsal portions of the cervical spinal cord. The analgesic effect of EA LI18 is better than that of EA ST36-GB34.


Assuntos
Eletroacupuntura , Pontos de Acupuntura , Animais , Interleucina-4 , Masculino , Cervicalgia , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-4 , Medula Espinal , Fator de Necrose Tumoral alfa
17.
Medicine (Baltimore) ; 98(40): e17126, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577702

RESUMO

BACKGROUND: The aim of this study was to investigate the role of n-acetyl cysteine (NAC) in the lipopolysaccharide (LPS)-mediated induction of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) synthesis by human periodontal ligament fibroblast cells (hPDLFs). In addition, we aimed to determine the involvement of the nuclear factor-kappa B (NF-κB) pathway in any changes in IL-1ß and TNF-α expression observed in response to LPS and NAC. METHODS: HPDLFs were obtained by primary culture. The culture medium used in this experiment was Dulbecco's Modified Eagle Medium (DMEM low-glucose). Cells were stimulated with various concentrations of NAC or LPS. Cell proliferation was measured at various time-points with the cell Counting Kit 8 (CCK-8) assay. mRNA levels of IL-1ß and TNF-α were determined by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Protein levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expression levels of NF-κB were measured by western blot and RT-qPCR. RESULTS: The results showed that LPS treatment in hPDLFs induced mRNA and protein expression of IL-1ß, TNF-α, and NF-κB. However, these effects were eliminated by pretreatment with NAC. Pretreatment with both NAC (1 mmol/L) and BAY11-7082 (10 µmol/L) significantly inhibited the NF-κB activity induced by LPS. CONCLUSION: NAC inhibits the LPS-mediated synthesis of tumor TNF-α and IL-1ß in hPDLFs, through the NF-κB pathway.


Assuntos
Acetilcisteína/farmacologia , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/biossíntese , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Ligamento Periodontal , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
18.
Medicine (Baltimore) ; 98(40): e17233, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577714

RESUMO

RATIONALE: The pathology of gouty arthritis and reactive arthritis (ReA) partially overlaps, and both diseases are characterized by the production of inflammatory cytokines associated with the activation of monocytes and macrophages. However, the precise cytokine profile of cases with a coexistence of both diseases is unknown, and there are few reports on the course of treatment in patients with both gouty arthritis and ReA. PATIENT CONCERNS: A 39-year-old man with a recurrent episode of gouty arthritis presented prednisolone-resistant polyarthritis with high level of C-reactive protein (CRP). He had the features of gouty arthritis such as active synovitis of the first manifestation of metatarsophalangeal (MTP) joints and the presence of monosodium urate (MSU) crystals from synovial fluid. But he also had the features of ReA such as the presence of tenosynovitis in the upper limb, the positivity of human leukocyte antigen (HLA)-B27, a history of sexual contact and positive findings of anti-Chlamydia trachomatis-specific IgA and IgG serum antibodies. DIAGNOSES: He was diagnosed with HLA-B27 associated Chlamydia-induced ReA accompanied by gout flares. INTERVENTIONS: He was treated with 180 mg/day of loxoprofen, 1 mg/day of colchicine, and 10 mg/day of prednisolone for gout flares. However, his polyarthritis worsened with an increased level of CRP (23.16 mg/dL). Accordingly, we added 500 mg/day of salazosulfapyridine followed by adalimumab (ADA) 40 mg once every 2 weeks. OUTCOMES: After starting ADA, the patient's symptoms and laboratory findings showed rapid improvement and he achieved clinical remission 1 month after initiation of ADA treatment. As of this writing, the patient's clinical remission has been maintained for >1 year. LESSONS: This case suggests that with exacerbation of arthritis during gouty arthritis, coexistence with other pathologies such as peripheral spondyloarthritis should be considered, and early intensive treatment including tumor necrosis factor inhibitors may be necessary.


Assuntos
Artrite Reativa/etiologia , Infecções por Chlamydia/complicações , Gota/complicações , Adulto , Artrite Reativa/tratamento farmacológico , Proteína C-Reativa/análise , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Citocinas/metabolismo , Gota/tratamento farmacológico , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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