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1.
Article in English | WPRIM | ID: wpr-922575

ABSTRACT

OBJECTIVE@#To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α).@*METHODS@#In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1β and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot.@*RESULTS@#In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1β, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05).@*CONCLUSION@#HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.


Subject(s)
Animals , Colitis, Ulcerative/drug therapy , Dextran Sulfate , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , NF-kappa B , Scutellaria baicalensis , Tumor Necrosis Factor-alpha
2.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 468-475, Oct.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350824

ABSTRACT

ABSTRACT Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18-69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5-2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5-2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Hydroxyurea , Anemia, Sickle Cell , Tumor Necrosis Factor-alpha , Oxidative Stress , Cytotoxicity, Immunologic , Dosage , Inflammation , Malondialdehyde , Neutrophils
3.
An. bras. dermatol ; 96(4): 447-450, July-Aug. 2021. graf
Article in English | LILACS | ID: biblio-1285096

ABSTRACT

Abstract Psoriasis is a chronic inflammatory disease that affects the skin variably, according to genetic and environmental factors. Some patients may benefit from systemic treatment with immunobiological agents, drugs that can be accompanied by several adverse effects. A case of a 58-year-old patient undergoing treatment for psoriasis with adalimumab for five years is reported. Alterations compatible with interstitial pneumonia were detected with important regression after adalimumab discontinuation. This case is relevant due to the scarcity of reports on late pulmonary adverse effect of anti-TNF treatment of psoriasis.


Subject(s)
Humans , Psoriasis/chemically induced , Psoriasis/drug therapy , Lung Diseases, Interstitial/chemically induced , Tumor Necrosis Factor-alpha , Adalimumab/adverse effects , Tumor Necrosis Factor Inhibitors , Middle Aged
4.
An. bras. dermatol ; 96(4): 477-481, July-Aug. 2021. graf
Article in English | LILACS | ID: biblio-1285095

ABSTRACT

Abstract Herpetic whitlow is a viral infection of the fingers caused by the herpes simplex virus. The disease has a bimodal age distribution, affecting children under 10 years of age and young adults between 20 and 30 years old. It can be easily mistaken for panaritium or bacterial cellulitis. In patients with AIDS, atypical, chronic and recurrent ulcerated lesions occur. The Tzanck test allows a quick and low-cost diagnosis of herpes simplex virus infection. The authors report the case of a child with AIDS with painful finger ulcers in which the diagnosis was confirmed by the Tzanck test.


Subject(s)
Humans , Psoriasis/chemically induced , Psoriasis/drug therapy , Lung Diseases, Interstitial/chemically induced , Tumor Necrosis Factor-alpha , Adalimumab/adverse effects , Tumor Necrosis Factor Inhibitors , Middle Aged
5.
Arq. gastroenterol ; 58(1): 107-113, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1248984

ABSTRACT

ABSTRACT BACKGROUND: The rates of postoperative endoscopic recurrence (PER) in patients with Crohn's disease (CD) are consistent. Anti-TNF therapy has been increasingly used in the postoperative setting, despite the lack of robust data in the literature on the measurement of trough levels and consequences of their use. OBJECTIVE: The aim of this review was to assess trough levels of infliximab (IFX) in CD patients after ileocolonic resections in correlation with the presence of PER. METHODS: We searched for studies that evaluated trough levels of IFX in patients with CD, who underwent ileocaecal resections, and correlated them with the presence of PER. We used MEDLINE through PubMed and CENTRAL Cochrane library databases, and after matching the inclusion criteria, the studies were methodologically evaluated with qualitative analysis of the data. RESULTS: A total of 155 studies were initially identified in the databases search and only four matched the inclusion criteria. They comprised one prospective cohort study, one randomized controlled trial and two retrospective cohort studies, the last one performed in pediatric patients. This evidence suggested the correlation of PER with low trough levels of IFX and the presence of antibodies to the drug. The quality of the evidence generated varied from very low to high, due to the heterogeneity found between the studies and the risks of bias that were identified. CONCLUSION: Low levels of IFX and the presence of antibodies to the drug were directly associated with increased PER rates in patients with CD, who underwent ileocolonic resections. Controlled and randomized clinical trials with adequate methodological quality are warranted to confirm the conclusions from this systematic review.


RESUMO CONTEXTO: As taxas de recorrência endoscópica pós-operatória em pacientes com doença de Crohn (DC) são significativas. A terapia anti-TNF é cada vez mais usada no cenário pós-operatório, apesar da escassez de dados na literatura sobre dosagem de níveis séricos e anticorpos da droga. OBJETIVO: Realizou-se uma revisão sistemática com o intuito de se avaliar níveis séricos de infliximabe (IFX) em pacientes com DC submetidos a ileocolectomia e correlacionar com a presença ou não de recorrência endoscópica da doença. MÉTODOS: Buscou-se por estudos que avaliaram o nível sérico do IFX em pacientes com DC, submetidos a ileocolectomias, correlacionando-os à presença de recorrência endoscópica pós-operatória. Utilizou-se as bases de dados MEDLINE via PubMed e CENTRAL Cochrane Library, e após atingirem os critérios de inclusão, os estudos foram avaliados metodologicamente e foi realizada análise qualitativa dos dados. RESULTADOS: Um total de 155 estudos foram identificados e apenas quatro atingiram os critérios de inclusão. Um era estudo de coorte prospectivo, o segundo era um ensaio clínico randomizado e dois eram estudos de coortes retrospectivas, sendo o último exclusivamente em pacientes pediátricos. As evidências encontradas tendem a confirmar a correlação da recorrência endoscópica a baixos níveis séricos de IFX e presença de anticorpos anti-droga. A qualidade da evidência gerada variou de muito baixa a alta, devido à heterogeneidade encontrada entre os estudos e o risco de viés identificado. CONCLUSÃO: Baixos níveis séricos do IFX e presença de anticorpos contra a droga estão associados a probabilidade aumentada de recorrência endoscópica pós-operatória nos pacientes com DC submetidos a ileocolectomias. Ensaios clínicos controlados e randomizados com adequada qualidade metodológica são necessários para confirmar as conclusões desta revisão.


Subject(s)
Humans , Child , Crohn Disease/surgery , Crohn Disease/drug therapy , Prospective Studies , Retrospective Studies , Tumor Necrosis Factor-alpha , Infliximab/therapeutic use
6.
Arq. bras. cardiol ; 116(3): 443-451, Mar. 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1248872

ABSTRACT

Resumo Fundamento: A citocina fator de necrose tumoral alfa (TNF-α) é elevada na hipertensão resistente (HAR), mas os efeitos dos inibidores de TNF-α nessa população ainda são desconhecidos. Objetivos: O objetivo deste estudo foi avaliar se uma única dose de infliximabe controlada por placebo reduz a pressão arterial (PA) de forma aguda em pacientes com HAR. Métodos: Realizamos um estudo cruzado, randomizado, duplo-cego e controlado por placebo em que pacientes com HAR receberam infliximabe ou placebo. O desfecho primário foi a alteração dos níveis de PA média em relação ao basal imediatamente após a infusão, obtida por avaliação hemodinâmica não invasiva contínua, batimento a batimento. Os desfechos secundários incluíram alterações em medidas de PA central, ambulatorial e em consultório, na função endotelial, e nos biomarcadores inflamatórios após 7 dias. O nível de significância aceito foi alfa=0,05. Resultados: Foram incluídos dez portadores de HAR. O resultado do desfecho primário demonstrou uma redução aguda dos níveis de PA média (média das diferenças ± desvio padrão = -6,3 ± 7,2 mmHg, p=0,02) em relação ao basal, após o uso de infliximabe, em comparação com o placebo. Os níveis de PA diastólica (-4,9 ± 5,5 mmHg, p=0,02), mas não os níveis de PA sistólica (-9,4 ± 19,7 mmHg, p=0,16), reduziram após a infusão de infliximabe. Não foram identificadas diferenças significativas nos demais parâmetros hemodinâmicos, nem nos resultados dos desfechos secundários, com exceção dos níveis de TNF-α, que aumentaram continuamente após o uso de infliximabe. Não foram relatados eventos adversos durante o protocolo. Conclusões: Uma dose única de infliximabe reduziu os níveis de PA média e diastólica imediatamente após sua infusão, em comparação com placebo em HAR. A terapia com anti-TNF-α foi considerada segura e bem tolerada. Os resultados desse estudo prova de conceito são geradores de hipótese e precisam ser investigados em maior detalhe. (Arq Bras Cardiol. 2021; 116(3):443-451)


Abstract Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. Objective: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. Methods: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. Results: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. Conclusions: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451)


Subject(s)
Humans , Tumor Necrosis Factor-alpha , Hypertension/drug therapy , Blood Pressure , Pilot Projects , Double-Blind Method
8.
Adv Rheumatol ; 61: 17, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152736

ABSTRACT

Abstract Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.(AU)


Subject(s)
Humans , Spondylitis, Ankylosing/etiology , Homocysteine/analysis , Case-Control Studies , Methotrexate/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use
9.
Article in Chinese | WPRIM | ID: wpr-879445

ABSTRACT

OBJECTIVE@#To investigate the expression and clinical significance of receptor interacting protein serine-threonine kinases 1 (RIPK1) in the nucleus pulposus of patients with lumbar disc herniation (LDH).@*METHODS@#Nucleus pulposus tissue specimens of 40 patients with LDH patients underwent surgical treatment from January 2016 to January 2018 as the case group, and nucleus pulposus tissue specimens of 30 patients with lumbar spine fracture underwent surgical treatment at the same time as the control group. The expression of RIPK1 mRNA and protein of receptor interaction were detected by polymerase chain reaction (PCR) and Western blot, respectively. The expression of RIPK1 protein in the nucleus pulposus were detected by immunohistochemical staining. The concentrations of RIPK1 and tumor necrosis factor-α (TNF-α) in nucleus pulposus were detected by ELISA method. The relationship between the concentrations of RIPK1, TNF-α in nucleus pulposus and the Pearce grade of LDH patients was analyzed by one-way ANOVA. The correlation between RIPK1 and TNF-α was analyzed by Pearson.@*RESULTS@#RIPK1 was weakly positively expressed in nucleus pulposus of control group, and RIPK1 protein was positively or strongly positively expressed in case group. The expression of RIPK1 mRNA in nucleus pulposus of case group was higher than that of control group (@*CONCLUSION@#The expression levels of RIPK1 mRNA and protein in the intervertebral disc tissues of LDH patients are higher than those of normal intervertebral disc tissues, and increased with the increase of Pearce grade, which may be an important factor involved in LDH inflammatory disease.


Subject(s)
Humans , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration , Intervertebral Disc Displacement/genetics , Nucleus Pulposus , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Tumor Necrosis Factor-alpha/metabolism
10.
Article in English | WPRIM | ID: wpr-922757

ABSTRACT

During the pathogensis of rheumatoid arthritis (RA), activated RA fibroblast-like synoviocytes (RA-FLSs) combines similar proliferative features as tumor and inflammatory features as osteoarthritis, which eventually leads to joint erosion. Therefore, it is imperative to research and develop new compounds, which can effectively inhibit abnormal activation of RA-FLSs and retard RA progression. Neohesperidin (Neo) is a major active component of flavonoid compounds with anti-inflammation and anti-oxidant properties. In this study, the anti-inflammation, anti-migration, anti-invasion, anti-oxidant and apoptosis-induced effects of Neo on RA-FLSs were explored to investigate the underlying mechanism. The results suggested that Neo decreased the levels of interleukin IL-1β, IL-6, IL-8, TNF-α, MMP-3, MMP-9 and MMP-13 in FLSs. Moreover, Neo blocked the activation of the MAPK signaling pathway. Furthermore, treatment with Neo induced the apoptosis of FLSs, and inhibited the migration of FLSs. It was also found that Neo reduced the accumulation of reactive oxygen species (ROS) induced by TNF-α. Taken together, our results highlighted that Neo may act as a potential and promising therapeutic drug for the management of RA.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Cell Movement , Cell Proliferation , Cells, Cultured , Fibroblasts , Hesperidin/analogs & derivatives , Humans , Synoviocytes , Tumor Necrosis Factor-alpha/genetics
11.
Frontiers of Medicine ; (4): 867-876, 2021.
Article in English | WPRIM | ID: wpr-922514

ABSTRACT

Sleep disturbances are common in patients with stroke, and sleep quality has a critical role in the onset and outcome of stroke. Poor sleep exacerbates neurological injury, impedes nerve regeneration, and elicits serious complications. Thus, exploring a therapy suitable for patients with stroke and sleep disturbances is imperative. As a multi-targeted nonpharmacological intervention, remote ischemic conditioning can reduce the ischemic size of the brain, improve the functional outcome of stroke, and increase sleep duration. Preclinical/clinical evidence showed that this method can inhibit the inflammatory response, mediate the signal transductions of adenosine, activate the efferents of the vagal nerve, and reset the circadian clocks, all of which are involved in sleep regulation. In particular, cytokines tumor necrosis factor α (TNFα) and adenosine are sleep factors, and electrical vagal nerve stimulation can improve insomnia. On the basis of the common mechanisms of remote ischemic conditioning and sleep regulation, a causal relationship was proposed between remote ischemic conditioning and post-stroke sleep quality.


Subject(s)
Brain Ischemia/complications , Humans , Stroke/complications , Treatment Outcome , Tumor Necrosis Factor-alpha
12.
Article in English | WPRIM | ID: wpr-922120

ABSTRACT

OBJECTIVE@#To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).@*METHODS@#The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.@*RESULTS@#AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).@*CONCLUSIONS@#AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.


Subject(s)
Animals , Disease Models, Animal , Heart Diseases , NF-kappa B , Rats , Rats, Sprague-Dawley , Saponins , Sepsis/drug therapy , Triterpenes , Tumor Necrosis Factor-alpha
13.
Article in Chinese | WPRIM | ID: wpr-921929

ABSTRACT

Osteoarthritis(OA) is one of the most common joint diseases. As Chinese society enters the age of aging, the incidence of OA has been soar year by year, and research on its pathogenesis has been continuously valued by researchers. Studies have found that inflammatory cytokines, mainly interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were responsible for the construction of OA inflammatory networks. It was also found that the overexpression of proteases, mainly matrix metalloproteinases(MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), was the direct cause of OA cartilage deficiency. What's more, signaling pathways such as stromal cell derived factor-1 (SDF-1) and Wnt, chondrocytic senescence and the senescence-associated secretory phenotype (SASP), chondrocyte apoptosis and autophagy, and estrogen all play significant roles in OA pathogenesis. This paper extensively reviews the research literature relevant to the pathogenesis of OA in recent years, and systematically expounds the pathogenesis of OA from two aspects:molecular level and cell level. At the end of the paper, we discussed and predicted some potential directions in the future clinical diagnosis and treatment of OA.


Subject(s)
Cartilage , Cartilage, Articular , Chondrocytes , Humans , Interleukin-1beta , Osteoarthritis/genetics , Signal Transduction , Tumor Necrosis Factor-alpha
14.
Article in Chinese | WPRIM | ID: wpr-921646

ABSTRACT

Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 μg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.


Subject(s)
Animals , Endothelial Cells/metabolism , Intercellular Adhesion Molecule-1/genetics , Mice , NF-kappa B/metabolism , Neoplasms , Polysaccharides , Reishi , Signal Transduction , T-Lymphocytes , Tumor Necrosis Factor-alpha
15.
Acta Physiologica Sinica ; (6): 901-908, 2021.
Article in Chinese | WPRIM | ID: wpr-921294

ABSTRACT

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.


Subject(s)
Alanine Transaminase , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Dexmedetomidine/pharmacology , Galactosamine/toxicity , Interleukin-6/blood , Lipopolysaccharides/toxicity , Liver , Male , Mice , Mice, Inbred BALB C , Microtubule-Associated Proteins/metabolism , Tumor Necrosis Factor-alpha/blood , Up-Regulation
16.
Article in Chinese | WPRIM | ID: wpr-888357

ABSTRACT

OBJECTIVE@#To observe the analgesic effect of lever positioning manipulation combined with pulsed electric field on patients with lumbar disc herniation and the influence on serum IL-1β and TNF-α.@*METHODS@#From January 2018 to March 2019, 58 patients with lumbar disc herniation were included in the study, which were randomly divided into observation group and control group by digital table method. Observation group of 29 cases, including 16 males and 13 females, aged (38.03±11.29) years old, were treated with lever positioning manipulation combined with pulsed electric field. The 29 cases in control group, including 17 males and 12 females, aged (38.21±9.16) years old, were treated with pulsed electric field. Both groups of patients were treated 3 times a week, once every other day, 3 times as a course of treatment. After 2 courses of treatment, the two groups of patients were scored before and after treatment by the numeric rating scales (NRS);at the same time, the serum levels of IL-1β and TNF-α were measured before and after treatment.@*RESULTS@#The NRS scores of observation group and control group were 4.21±1.76, 4.66±1.61 before treatment, and 1.28±0.84, 2.10±1.35 after treatment, respectively. The NRS scores of the observation group after treatment was significantly lower than that of the control group (@*CONCLUSION@#The lever positioning manipulation combined with pulsed electric field has a good analgesic effect on patients with lumbar disc herniation, and it has a significant impact on the patient's serum IL-1β and TNF-α concentration, which can be used as a clinical guide. However, the synergistic effect of lever positioning technique combined with pulsed electric field and guidelines for clinical treatment need further research.


Subject(s)
Adult , Female , Humans , Intervertebral Disc Degeneration , Intervertebral Disc Displacement/therapy , Male , Middle Aged , Tumor Necrosis Factor-alpha
17.
Article in Chinese | WPRIM | ID: wpr-887991

ABSTRACT

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.


Subject(s)
Apoptosis , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Plant Extracts , Signal Transduction , Tumor Necrosis Factor-alpha/genetics
18.
Article in Chinese | WPRIM | ID: wpr-887482

ABSTRACT

OBJECTIVE@#To observe the effect of long-term moxa smoke exposure of different concentrations on olfactory function in rats, and provide experimental basis of safety study of moxa smoke produced by moxibustion.@*METHODS@#Forty SD rats were randomly divided into a normal control group, a low-concentration moxa smoke group, a moderate-concentration moxa smoke group and a high-concentration moxa smoke group, 10 rats in each one. The rats in the moxa smoke groups were put into three plexiglass moxibustion boxes with different moxa smoke concentrations, 4 hours per times, twice a day for 90 days. The general state of rats was evaluated before and during the experiment. After the intervention, the olfactory function was evaluated by two-bottle experiment (TBE); the morphology of nasal mucosa was observed by HE staining; the apoptosis of olfactory epithelial cells in nasal mucosa was detected by TUNEL method; the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA method.@*RESULTS@#In the late stage of moxa smoke exposure (45-90 days into intervention), the behavioral activity of rats in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was weaker than that in the normal control group, and their response to stimulation was strong, and their mental state was worse. After intervention, the drinking rate of vinegar-water mixture in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was higher than that in the normal control group and the low-concentration moxa smoke group (@*CONCLUSION@#The long-term exposure to low, moderate and high concentrations of moxa smoke could cause pathological changes in nasal mucosa and increase the serum levels of IL-1, IL-6 and TNF-α; the moderate and high concentrations of moxa smoke exposure could cause a series of damage to olfactory function and reduce olfactory sensitivity in rats.


Subject(s)
Animals , Interleukin-1 , Interleukin-6 , Rats , Rats, Sprague-Dawley , Smoke/adverse effects , Tumor Necrosis Factor-alpha
19.
Article in Chinese | WPRIM | ID: wpr-879137

ABSTRACT

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1β and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.


Subject(s)
Animals , Bronchitis, Chronic/drug therapy , Drugs, Chinese Herbal/pharmacology , Glutathione Peroxidase , Lipopolysaccharides , Lung , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha
20.
Article in Chinese | WPRIM | ID: wpr-879076

ABSTRACT

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.


Subject(s)
Animals , Dendrobium , Intestinal Mucosa , Lipopolysaccharides , Male , Mice , NF-kappa B , Powders , Tumor Necrosis Factor-alpha/genetics
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