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1.
Gene ; 806: 145921, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454033

RESUMO

Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a ß-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via ß-adrenergic receptors in vivo.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Interleucina-10/genética , Extratos Vegetais/farmacologia , Receptores Adrenérgicos beta/genética , Administração Oral , Animais , Modelos Animais de Doenças , Efedrina/farmacologia , Regulação da Expressão Gênica , Injeções Intraperitoneais , Interleucina-10/agonistas , Interleucina-10/imunologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poli I-C/administração & dosagem , Poli I-C/antagonistas & inibidores , Receptores Adrenérgicos beta/imunologia , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
2.
Ann Saudi Med ; 41(5): 285-292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618606

RESUMO

BACKGROUND: Adalimumab is a fully humanized monoclonal antibody inhibitor of tumor necrosis factor-a used to treat various autoimmune disorders. Adalimumab poses a risk for tuberculosis (TB) infection, especially in countries where TB is endemic. OBJECTIVE: Determine the rate of TB infection after adalimumab therapy in Saudi Arabia. DESIGN: Medical record review. SETTINGS: Tertiary care center in Riyadh. PATIENTS AND METHODS: Demographic and clinical data were retrieved from the electronic healthcare records of all patients who received adalimumab treatment from 2015 to 2019. MAIN OUTCOME MEASURES: Occurrence of TB after adalimumab therapy. SAMPLE SIZE: 410 patients (median ([QR] age, 37 [28], range 4-81 years), 40% males RESULTS: Rheumatoid arthritis was the most frequent indication (n=153, 37%). The patients were followed for a mean of 36 (8.9) months. No case of TB infection or reactivation was observed. An inter-feron-gamma release assay (IGRA) was requested in 353/391 (90.3%) patients, prior to initiating therapy. The IGRA was positive in 26 cases (6.6%). The IGRA-positive patients received isoniazid prophylactically. Bacterial infectious complications of adalimumab therapy occurred in 12 (2.9%) patients. Urinary tract infection was the most frequent complication (culture requested in 48 patients, positive in 8). CONCLUSION: Adalimumab treatment was not associated with a risk of TB disease or TB reactivation in our cohort over the follow-up observation period. No TB reactivation occurred with adalimumab therapy when TB prophylaxis was used. The positive IGRA rate in patients on adalimumab treatment was low (7%). LIMITATIONS: Single center and one geographical area in Saudi Arabia. CONFLICT OF INTEREST: None.


Assuntos
Artrite Reumatoide , Tuberculose Latente , Tuberculose , Adalimumab/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Tuberculose Latente/induzido quimicamente , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Masculino , Pessoa de Meia-Idade , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfa , Adulto Jovem
3.
Anal Chim Acta ; 1182: 338909, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34602194

RESUMO

Tumour Necrosis Factor (TNF-α) is a pro-inflammatory cytokine having key roles in cell death, differentiation, survival, proliferation, migration and is a modulator of immune system. Therefore, TNF-α is an ideal biomarker for several disease diagnosis including cancer. However, out of all the biomarkers of cancer, TNF-α) is less explored for cancer detection. Only a few reports are available of developing biosensors for TNF-α targeting in human serum samples. Also, Carbon Dots (CDs) remains less explored in biosensor application. In this regard, for the first time, a sensitive and low-cost electrochemical biosensor based on CDs has developed. CDs were synthesized by simple yet facile microwave pyrolysis. Poly methyl methacrylate (PMMA) was selected as the matrix to hold CDs to fabricate the biosensing platform. This novel CD-PMMA nanocomposite featuring excellent biocompatibility, exceptional electrocatalytic conductivity, and large surface area. CD-PMMA was applied as transducing material to efficiently conjugate antibodies specific towards TNF-α and fabricate electrochemical immunosensor for specific detection of TNF-α. The fabricated immunosensor was used for the detection of TNF-α within a wide dynamic range of 0.05-160 pg mL-1 with a lower detection limit of 0.05 pg mL-1 and sensitivity of 5.56 pg mL-1 cm-2. Furthermore, this CDs based immunosensor retains high sensitivity, selectivity, and stability. This immunosensor demonstrated a high correlation with the conventional technique, Enzyme-Linked Immunosorbent Assay for early screening of cancer patient serum samples.


Assuntos
Técnicas Biossensoriais , Neoplasias , Carbono , Técnicas Eletroquímicas , Humanos , Imunoensaio , Limite de Detecção , Neoplasias/diagnóstico , Fator de Necrose Tumoral alfa
4.
World J Gastroenterol ; 27(35): 5946-5957, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34629811

RESUMO

BACKGROUND: Crohn's disease (CD) is an incurable intestinal disorder with unclear etiology and pathogenesis. Currently, there is a lack of specific biomarkers and drug targets for CD in clinical practice. It is essential to identify the precise pathophysiological mechanism of CD and investigate new therapeutic targets. AIM: To explore a new biomarker and therapeutic target for CD and verify its role in the CD pathological mechanism. METHODS: Proteomics was performed to quantify the protein profile in the plasma of 20 CD patients and 20 matched healthy controls. Hub genes among the selected differentially expressed proteins (DEPs) were detected via the MCODE plugin in Cytoscape software. The expression level of one hub gene with an immunoregulatory role that interested us was verified in the inflamed intestinal tissues of 20 CD patients by immunohistochemical analysis. After that, the effects of the selected hub gene on the intestinal inflammation of CD were identified in a CD cell model by examining the levels of proinflammatory cytokines by enzyme-linked immunosorbent assays and the expression of the NF-κB signalling pathway by quantitative real-time PCR analysis and Western blot assays. RESULTS: Thirty-five DEPs were selected from 393 credible proteins identified by proteomic analysis. Among the DEPs, fibrinogen-like protein 1 (FGL1), which attracted our attention due to its function in the regulation of the immune response, had 1.722-fold higher expression in the plasma of CD patients and was identified as a hub gene by MCODE. Furthermore, the expression of FGL1 in the intestinal mucosal and epithelial tissues of CD patients was also upregulated (P < 0.05). In vitro, the mRNA levels of FGL1 and NF-κB; the protein expression levels of FGL1, IKKα, IKKß, p-IKKα/ß, p-IκBα, and p-p65; and the concentrations of the proinflammatory cytokines IL-1ß, IL-6, IL-17, and TNF-α were increased (P < 0.05) after stimulation with lipopolysaccharide, which were reversed by knockdown of FGL1 with siRNA transfection (P < 0.05). Conversely, FGL1 overexpression enhanced the abovementioned results (P < 0.05). CONCLUSION: FGL1 can induce intestinal inflammation by activating the canonical NF-κB signalling pathway, and it may be considered a potential biomarker and therapeutic target for CD.


Assuntos
Doença de Crohn , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Fibrinogênio , Humanos , NF-kappa B , Proteômica , Fator de Necrose Tumoral alfa
5.
Ann Palliat Med ; 10(8): 8858-8868, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488373

RESUMO

BACKGROUND: As the mainstay treatment for coronary heart disease (CHD), aspirin alone is reported to be less effective than in combination when treating CHD. The aim of this analysis was to systematically evaluate the efficacy and safety of aspirin in combination with other drugs for the treatment of CHD, as well as its effect on the levels of inflammatory factors. METHODS: Electronic databases were searched from 2011 to 2021 and randomized controlled trials (RCTs) on aspirin in CHD patients were included in our study. Data was statistically analyzed using Stata 16.0 (StataCorp). RESULTS: A total of 13 RCTs were included, with a total of 1,442 patients. Compared with control group (aspirin alone) group, the response rate in the treatment group (aspirin in combination with other drugs) was significantly improved [odds ratio (OR) =5.11; 95% confidence interval (CI): 3.56-7.35], while the incidence of adverse reactions was markedly decreased (OR =0.36; 95% CI: 0.25-0.53). Before treatment, no significant differences were identified in the levels of inflammatory factors between the groups The inflammatory factors included C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). After treatment, CRP and TNF-α levels were significantly lower in both groups compared with those before treatment. However, there was no statistically significant difference in IL-6 levels after treatment between the groups. DISCUSSION: Aspirin is effective in the treatment of CHD, both alone and in combination. However, the latter has higher clinical efficacy and safety, and can significantly reduce the level of inflammatory factors in CHD patients.


Assuntos
Aspirina , Doença das Coronárias , Aspirina/uso terapêutico , Proteína C-Reativa , Doença das Coronárias/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Fator de Necrose Tumoral alfa
6.
Ann Palliat Med ; 10(8): 9078-9087, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488393

RESUMO

BACKGROUND: Periodontitis (PD) is a chronic inflammatory disease caused by infection of the periodontal supporting tissues. Clinical studies have reported that rheumatoid arthritis (RA) patients have a higher prevalence of PD. This study aimed to explore the correlation between RA and PD. METHODS: A total of 307 RA patients (RA group) and 324 healthy individuals (control group) who received physical examinations during the same period were recruited to this study. The incidence of PD in the two groups was analyzed, and the periodontal disease index (PDI) and bleeding on probing (BOP) were recorded. Then, 42 RA patients with PD and 56 control group patients with PD were selected for further analysis. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the gingival crevicular fluid (GCF) of the two groups. For patients with both RA and PD, the level of serum C-reactive protein (CRP) and the duration of morning stiffness were also recorded. RESULTS: The prevalence of PD in the RA group (51.5%) was significantly higher than that in the control group (31.2%), and the prevalence of PD also increased notably with the increase of age and the duration of the disease in RA patients. The levels of TNF-α and IL-1ß in the PDI and the GCF in the concurrent RA and PD group were significantly higher than those in the PD group (P<0.05). Partial correlation analysis showed that TNF-α in the GCF positively correlated with the BOP of patients with RA and PD. Multiple linear regression analysis showed that the level of TNF-α in the GCF and serum CRP were independent influencing factors of the level of IL-1ß in the GCF (the r values were 1.074 and 3.851, respectively; P<0.01). CONCLUSIONS: The presence of RA can increase risk of PD occurrence and is positively correlated with the levels of IL-1ß and TNF-α in the GCF.


Assuntos
Artrite Reumatoide , Periodontite , Líquido do Sulco Gengival/química , Humanos , Interleucina-1beta/análise , Periodontite/epidemiologia , Fator de Necrose Tumoral alfa
7.
Curr Microbiol ; 78(10): 3720-3732, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34468852

RESUMO

Infection with Helicobacter pylori (H. pylori) leads to a fork in the road situation where it is critical and complex to judge the fate of the cell. We propose for the first time an in silico representation of a protein level network model that can unfold the mystery behind the cell fate decision between inflammation or cell proliferation or cell death. Upon infection TNF inducible protein α (Tip α) is internalised after binding with the cell surface receptor Nucleolin which is overexpressed on the cell surface thereby activating the Ras pathway. Tip α, Nucleolin and Ras decides the cell fate for apoptosis or abnormal cell proliferation along with ulcers in the gastric tract, hence we term it as the "death triad", which otherwise triggers the inflammatory pathway through downstream signalling of NF-κß. A series of proteins involved in the signalling cascade are portrayed through compartmentalization of the bacteria and the gut wall. The depicted network works synchronously toward an overarching goal of deciding between apoptosis or inflammation or proliferation. The model has been validated by simulating it with existing transcriptomic data along with clinical findings from patients infected with H. pylori across different regions in India. The results clearly indicate that for a short period of time there is increased binding of Tip α to Nucleolin and the receptor starts to saturate. This increases the tenacity of binding and the cell triggers an inflammatory cascade reaction which involves proinflammatory cytokines such as TNF α thereby progressing to inflammation by activating NF-κß downstream. On the other hand, Ras involved in interaction with nucleolin can be present both in its activated or inactivated state. Binding of Tip α as a monomer leads to desensitization of Nucleolin leading to cell survival and proliferation.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Helicobacter , Helicobacter pylori , Proteínas ras/metabolismo , Apoptose , Mucosa Gástrica , Humanos , Inflamação , Fosfoproteínas , Proteínas de Ligação a RNA , Fator de Necrose Tumoral alfa
8.
Clin Infect Dis ; 73(5): 793-801, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492697

RESUMO

BACKGROUND: Early and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge because of traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production have shown significant promise as alternative means of detecting and distinguishing active disease from latent infection. We queried the diagnostic ability of phenotypic markers on Mtb-specific cytokine-producing immune cell subsets for identifying active TB. METHODS: Subjects belonging to the following groups were recruited: pulmonary and extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral blood mononuclear cells. Clinical performance of the identified biomarker was evaluated using whole blood in a blinded validation cohort comprising 165 individuals. RESULTS: Cytokine secreting frequencies of Mtb-specific cluster of differentiation 4-positive (CD4+) T cells with CD38+CD27- phenotype clearly distinguished infected individuals with active tuberculosis from those without disease. Tumor necrosis factor-α (TNF-α) secretion from CD38+CD27-CD4+ T cells upon stimulation with ESAT6/CFP10 peptides had the best diagnostic accuracy at a cutoff of 9.91% (exploratory: 96.67% specificity, 88.46% sensitivity; validation: 96.15% specificity, 90.16% sensitivity). Additionally, this subset differentiated treatment-naive patients with TB from individuals cured of TB following completion of anti-TB therapy. CONCLUSIONS: Mtb-specific CD38+CD27-TNF-α +CD4+ T-cell subset is a robust biomarker both for diagnosing TB and assessing cure.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Antígenos de Bactérias , Biomarcadores , Linfócitos T CD4-Positivos , Humanos , Tuberculose Latente/diagnóstico , Leucócitos Mononucleares , Fator de Necrose Tumoral alfa
9.
J Evid Based Dent Pract ; 21(3): 101528, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34479676

RESUMO

OBJECTIVE: Chronic periodontitis (CP), aggressive periodontitis (AP), and peri-implantitis (PI) are chronic inflammatory diseases. Tumor necrosis factor-α (TNF-a) is an effective immune inflammatory mediator. Several studies have been conducted to explore the association between the TNF-α (G-308A) polymorphism and susceptibility to CP, AP, and PI. Our objective was to examine whether the TNF-α (G-308A) polymorphism is related to these diseases. METHODS: We conducted a meta-analysis to investigate the association between the TNF-α (G-308A) polymorphism and CP, AP, and PI. The PubMed, Embase, CNKI, and Web of Science electronic databases were searched for studies published from inception to August 11, 2020; the reference lists of included studies were also searched. The included studies were assessed in the following genetic models: dominant model, recessive model, allelic model, heterozygous model, and homozygous model. RESULTS: Forty articles (50 comparisons) with 2243 CP, 824 AP, 615 PI, 795 healthy peri-implant, and 3575 healthy controls were considered for the TNF-α (G-308A) polymorphism in this meta-analysis. Variant A of TNF-α (G-308A) was associated with increased AP risk in the general population, especially in Asians, and this polymorphism was significantly associated with elevated risk of CP in Asians and Caucasians. There was no association between the A allele and PI risk. None of the contrasts of the genetic model yielded a significant finding in Latin Americans. Different genotyping methods may affect the association between the TNF-α (G-308A) polymorphism and these diseases. CONCLUSION: These findings supported that variant A of the TNF-α (G-308A) polymorphism may contribute to CP and AP susceptibility, particularly in Asians and Caucasians. More efforts and further studies with larger sample sizes will be required to validate the risk of CP, AP, and PI.


Assuntos
Periodontite Agressiva , Periodontite Crônica , Peri-Implantite , Fator de Necrose Tumoral alfa/genética , Periodontite Agressiva/genética , Periodontite Crônica/genética , Humanos , Peri-Implantite/genética , Polimorfismo de Nucleotídeo Único
10.
RMD Open ; 7(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34489323

RESUMO

BACKGROUND: The close relationship between joints and gut inflammation has long been known and several data suggest that dysbiosis could link spondyloarthritis (SpA) to inflammatory bowel diseases (IBD). The introduction of biological drugs, in particular tumour necrosis factor inhibitors (TNFi), revolutionised the management of both these diseases. While the impact of conventional drugs on gut microbiota is well known, poor data are available about TNFi. AIM: To investigate the impact of TNFi on gut microbiota. METHODS: We evaluated 20 patients affected by enteropathic arthritis, naïve for biological drugs, treated with TNFi at baseline and after 6 months of therapy. All patients followed a Mediterranean diet. Patients performed self-sampling of a faecal sample at baseline and after 6 months of therapy. NGS-based ITS and 16S rRNA gene sequencing was performed, followed by the taxonomic bioinformatics analysis. RESULTS: After 6 months of therapy, we detected a remarkable increase in Lachnospiraceae family (Δ +10.3, p=0.04) and Coprococcus genus (Δ +2.8, p=0.003). We also noted a decreasing trend in Proteobacteria (Δ -8.0, p=0.095) and Gammaproteobacteria (Δ -9, p=0.093) and an increasing trend in Clostridia (Δ +8.2, p=0.083). We did not find differences between TNFi responders (SpA improvement or IBD remission achieved) and non-responders in terms of alpha and beta diversity. CONCLUSIONS: Our findings are consistent with the hypothesis that TNFi therapy tends to restore the intestinal eubiosis.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Espondilartrite , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , RNA Ribossômico 16S/genética , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
11.
Clin Lab ; 67(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542974

RESUMO

BACKGROUND: Inflammatory responses have been suggested to be associated with coronavirus disease 2019 (COVID-19). This study investigated the inflammatory markers and cytokines in COVID-19 according to its severity. METHODS: We enrolled 49 patients with COVID-19, who were classified as either moderate or critical cases. Serum or plasma interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) levels were measured. RESULTS: Lactate dehydrogenase, ferritin, C-reactive protein, and procalcitonin levels were significantly higher in the critical group than in the moderate group (p < 0.001). IL-6 and TNF-α levels were significantly higher in the critical group, with elevated IL-6 levels from the first to third weeks after confirmed PCR (p < 0.05). CONCLUSIONS: Inflammatory markers and cytokines were increased in COVID-19 and closely related to the severity of the disease. We recommend early active monitoring of IL-6 levels along with inflammatory markers for severe COVID-19.


Assuntos
COVID-19 , Citocinas , Biomarcadores , Humanos , SARS-CoV-2 , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa
12.
Oral Health Prev Dent ; 19(1): 481-488, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34585873

RESUMO

PURPOSE: The authors hypothesise that whole saliva soluble-urokinase-type plasminogen-activator receptor (suPAR) and tumor necrosis factor-alpha (TNF-α) levels are higher in patients with poorly-controlled than well-controlled type-2 diabetes mellitus (DM) and non-diabetic controls. The aim was to assess the periodontal clinicoradiographic status and whole-salivary suPAR and TNF-α levels in type-2 diabetic and non-diabetic individuals. MATERIALS AND METHODS: Patients with and without type-2 DM were included. In all patients, hemoglobin A1c (HbA1c) levels were measured. Participants were divided into 4 groups. Group 1: patients with poorly controlled type-2 DM; group 2: patients with well-controlled type-2 DM; group 3: non-diabetic patients with periodontitis; group 4: non-diabetic patients without periodontitis. Clinicoradiographic periodontal parameters (plaque index [PI], gingival index [GI], clinical attachment loss [AL], probing depth [PD] and mesial and distal marginal bone loss [MBL]) were measured. The whole saliva total protein concentration (TPC) and suPAR as well as TNF-α levels were measured. The level of statistical significance was set at p < 0.01. RESULTS: One hundred patients (25 patients per group) were included. Scores of PI (p < 0.01), GI (p < 0.01), clinical AL (p < 0.01), PD (p < 0.01), number of missing teeth and mesial (p < 0.01) and distal (p < 0.01) MBL were statistically significantly higher in group 1 than in groups 2-4. Scores of PI, GI, clinical AL, PD, mesial and distal MBL, and numbers of missing teeth were higher in group 3 (p < 0.01) than in groups 2 and 4. The whole saliva TPC, suPAR and TNF-α levels were statistically significantly higher among patients in group 1 (p < 0.01) than in groups 2-4. CONCLUSION: Patients with poorly-controlled type-2 DM presented with poorer clinicoradiographic periodontal status and increased whole saliva levels of suPAR, TNF-α and TPC compared with patients with well-controlled type-2 DM and non-diabetic individuals.


Assuntos
Diabetes Mellitus Tipo 2 , Fator de Necrose Tumoral alfa , Índice de Placa Dentária , Humanos , Plasminogênio , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Saliva , Ativador de Plasminogênio Tipo Uroquinase
13.
J Appl Oral Sci ; 29: e20210160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34586188

RESUMO

OBJECTIVE: This study aims to evaluate the effect of ellagic acid (EA) by measuring the levels of alveolar bone resorption and inflammatory and oxidative stress markers in the periodontal tissues and serum on the periodontal repair process related to experimental periodontitis in rats. METHODOLOGY: Forty Wistar rats were divided into four study groups as follows: Group 1=healthy control (n=10); Group 2=EA control (15 mg/kg)(n=10); Group 3=periodontitis (n=10); Group 4=periodontitis+EA (15 mg/kg) (n=10). The periodontitis model was established by ligating bilateral mandibular first molars for 14 days. Then, rats were given normal saline or EA for another 14 days by gavage administration. Serum and gingiva myeloperoxidase (MPO) activity, 8-hydroxydeoxyguanosine(8-OHdG), and glutathione (GSH) levels were analyzed by ELISA. Immunohistochemical analysis was used to detect Interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) immunoreactivities in the periodontal tissues. Alveolar bone loss (ABL) and attachment loss (AL) was evaluated by histomorphometry analysis. RESULTS: ABL and AL were statistically higher in group 3 than in groups 1, 2 and 4 and in group 4 than in groups 1 and 2 (p<0.05). MPO activities in gingival tissue and serum were significantly increased in group 3 compared to groups 1 and 2 (p<0.05). Significantly higher serum GSH levels, lower gingiva, and serum 8-OHdG levels, and MPO activity were observed in group 4 compared to group 3 (p<0.05). Rats with periodontitis (group 3) expressed significantly higher immunoreactivities of IL-6 and TNF-α and lower IL-10 immunoreactivity compared to those other groups (p<0.05). IL-6 and TNF-α immunoreactivities significantly decreased and IL-10 immunoreactivity increased in group 4 after the use of EA compared to group 3 (p<0.001). CONCLUSIONS: Our findings showed that EA provides significant improvements on gingival oxidative stress and inflammatory markers and alveolar bone resorption in the repair process associated with experimental periodontitis. Therefore, EA may have a therapeutic potential on periodontitis.


Assuntos
Perda do Osso Alveolar , Periodontite , Animais , Ácido Elágico/farmacologia , Interleucina-1beta , Periodontite/tratamento farmacológico , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 933-937, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590559

RESUMO

OBJECTIVE: To investigate the role and regulatory mechanism of triggering receptor expressed on myeloid cell 2 (TREM2) in mice lung ischemia/reperfusion injury (LIRI). METHODS: Thirty-six healthy male C57BL/6 mice were divided into six groups according to the random number method (n = 6): normal control group, and LIRI 2, 6, 12, 24, 48 hours group. Mice LIRI models were established by clamping the left hilum. The wet/dry weight ratio (W/D) of left lung tissue was measured. Lung injury was observed and evaluated by hematoxylin-eosin (HE) staining and electron microscopy. The levels of interleukins (IL-1ß, IL-18) in lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TREM2 and caspase-1 were determined by polymerase chain reaction (PCR). The protein expressions of TREM2, caspase-1, Gasdermin-D (GSDMD) were determined by Western blotting. RESULTS: At 2 hours after LIRI, lung injury began to appear, the lung ultrastructure changed, and the lung injury score increased; at 6 hours, the degree of lung injury was the most serious; after 12 hours, the lung injury gradually reduced and the lung injury score gradually decreased. Compared with the normal control group, lung W/D ratio and lung injury score of LIRI 2, 6, 12, 24, 48 hours groups were significantly higher, the differences were statistically significant (lung W/D ratio: 7.06±0.52, 8.34±0.17, 6.42±0.35, 5.34±0.25, 5.59±0.45 vs. 4.69±0.23; lung injury score: 5.50±0.54, 9.75±0.89, 5.88±0.84, 3.63±0.74, 4.13±0.64 vs. 1.13±0.35, all P < 0.05). Compared with the normal control group, the levels of IL-1ß and IL-18 in lung tissue were significantly increased at 2 hours after LIRI, reached a peak at 6 hours [IL-1ß (ng/L): 502.76±12.25 vs. 56.50±8.07, IL-18 (ng/L): 414.02±10.75 vs. 81.63±5.29, both P < 0.05], then decreased gradually, and were still significantly higher than the normal control group at 48 hours. The PCR and Western blotting showed that the expression of TREM2 was significantly lower than that in the normal control group at 2 hours after LIRI, and reached a valley at 6 hours [TREM2 mRNA (2-ΔΔCt): 0.47±0.05 vs. 1.02±0.05, TREM2/GAPDH: 0.23±0.13 vs. 0.48±0.17, both P < 0.05], then gradually increased, and reached the peak at 24 hours [TREM2 mRNA (2-ΔΔCt): 3.98±0.15 vs. 1.02±0.05, TREM2/GAPDH: 0.71±0.17 vs. 0.48±0.17, both P < 0.05]. The trend of expression of caspase-1 and GSDMD were opposite to that of TREM2, which increased at first and then decreased, and reached a peak at 6 hours after reperfusion [caspase-1 mRNA (2-ΔΔCt): 2.20±0.13 vs. 1.01±0.02, caspase-1/GAPDH: 0.64±0.02 vs. 0.20±0.06, GSDMD/GAPDH: 1.23±0.01 vs. 0.87±0.02, all P < 0.05]. CONCLUSIONS: TREM2 might be involved in LIRI in mice. The mechanism may be related to the effect of TREM2 on caspase-1-mediated pyroptosis.


Assuntos
Lesão Pulmonar , Traumatismo por Reperfusão , Animais , Pulmão , Masculino , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides , Receptores Imunológicos , Fator de Necrose Tumoral alfa
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 979-984, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590567

RESUMO

OBJECTIVE: To observe the protective effect of Angong Niuhuang pill on brain function of rats with sepsis, explore its protective mechanism, and provide the experimental basis for clinical application of Angong Niuhuang pill in the treatment of sepsis-associated encephalopathy (SAE). METHODS: Thirty male Sprague-Dawley (SD) rats were divided into sham operation group, sepsis model group and Angong Niuhuang pill group according to random number table method, with 10 rats in each group. The sepsis model was established by cecal ligation and puncture (CLP); rats in sham operation group received open and closed abdomen. The rats in the Angong Niuhuang pill group were given Angong Niuhuang pill (0.3 g/kg) by gastric irrigation daily for 3 days before CLP, and the drugs were administrated 12 hours after modeling again. After 24 hours of CLP, the neuroreflex scores were evaluated, white blood cell count (WBC), the levels of serum neuron-specific enolase (NSE) and S100ß were detected. Then the brain tissue was harvested. After hematoxylin-eosin (HE) staining, the pathological changes of brain tissue were observed under the light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue were detected by polymerase chain reaction. RESULTS: Compared with the sham operation group, the total score of neuroreflex scores in the sepsis model group and the Angong Niuhuang pill group were significantly reduced (4.43±1.40, 6.57±1.90 vs. 9.40±0.84, both P < 0.05), WBC, serum NSE, S100ß were significantly increased [WBC (×109/L): 8.07±1.32, 5.84±0.94 vs. 3.60±0.32; NSE (µg/L): 1.04±0.14, 0.61±0.07 vs. 0.16±0.04; S100ß (ng/L): 255.624±30.25, 97.72±15.41 vs. 46.88±12.03, all P < 0.05], and the mRNA expressions of IL-6 and TNF-α in brain tissue were significantly increased [IL-6 mRNA (2-ΔΔCt): 5.668±2.195, 3.605±1.014 vs. 0.997±0.329; TNF-α mRNA (2-ΔΔCt): 18.996±0.913, 1.746±0.710 vs. 0.674±0.132, all P < 0.05]. Compared with the sepsis model group, the total score of neuroreflex scores in the Angong Niuhuang pill group was significantly increased (6.57±1.90 vs. 4.43±1.40, P < 0.05), WBC, serum NSE, S100ß concentration, and the mRNA expressions of IL-6 and TNF-α in the brain were significantly reduced [WBC (×109/L): 5.84±0.94 vs. 8.07±1.32, NSE (µg/L): 0.61±0.07 vs. 1.04±0.14, S100ß (ng/L): 97.72±15.41 vs. 255.62±30.25, IL-6 mRNA (2-ΔΔCt): 3.605±1.014 vs. 5.668±2.195, TNF-α mRNA (2-ΔΔCt): 1.746±0.710 vs. 18.996±0.913, all P < 0.05]. Brain histopathological observation showed that the hippocampal neurons in the sepsis model group were disordered arrangement, a large number of neuronal nuclei were contracted, and the tissue was loose with obvious edema. Compared with the sepsis model group, the Angong Niuhuang pill group had less nuclear shrinkage and tissue edema. CONCLUSIONS: The pretreatment of the Angong Niuhuang pill can improve the brain dysfunction of septic rats and reduce the expression of pro-inflammatory cytokines in the brain. It is speculated that the Angong Niuhuang pill can protect the brain function in sepsis by inhibiting the inflammatory reaction in the brain.


Assuntos
Encefalopatia Associada a Sepse , Sepse , Animais , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/complicações , Sepse/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
16.
Molecules ; 26(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500571

RESUMO

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with the addition of isoprenaline (3 mg/kg/day, subcutaneously) during the last 10 days of treatment. At the end of 14 days of treatment, blood samples were collected, the hearts were excised under anesthesia and weighed. Heart tissue homogenate was used to measure superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Furthermore, the serum activities of cardiac markers, including lactate dehydrogenase, creatine kinase, and cardiac troponin, were checked. Moreover, inflammatory markers including tumor necrosis factor alpha, interleukin one beta, interleukin six, and kappa bp65 subunit were assessed. Rats that received GO, DADS, and CAR exhibited a significant increase in the cardiac antioxidant enzyme activities with a simultaneous decrease in serum cardiac markers enzymes and inflammatory markers. The TBARS were significantly reduced in rats that received treatment. The addition of carvedilol to GO or DADS significantly elevated antioxidant activities and decreased the release of cardiac enzymes into blood circulation. Both DADS and GOl were almost similar in efficacy, indicating the potential role of DADS in garlic oil-mediated cardioprotection. Combining GO or DADS with CAR increased CAR's cardioprotective impact and protected rats from developing ISO-induced myocardial infarction.


Assuntos
Compostos Alílicos/farmacologia , Cardiotônicos/farmacologia , Carvedilol/farmacologia , Dissulfetos/farmacologia , Alho/química , Coração/diagnóstico por imagem , Isoproterenol/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Modelos Animais de Doenças , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Biomed Res Int ; 2021: 4604856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527737

RESUMO

IFN-γ licensing to mesenchymal stem cells (MSCs) is applied to enhance the therapeutic potential of MSCs. However, although the features of MSCs are affected by several stimuli, little information is available on changes to the therapeutic potential of IFN-γ-licensed differentiated MSCs during xenogeneic applications. Therefore, the present study is aimed at clarifying the effects of adipogenic/osteogenic differentiation and IFN-γ licensing on the in vitro immunomodulatory and migratory properties of porcine bone marrow-derived MSCs in xenogeneic applications using human peripheral blood mononuclear cells (PBMCs). IFN-γ licensing in differentiated MSCs lowered lineage-specific gene expression but did not affect MSC-specific cell surface molecules. Although indoleamine 2,3 deoxygenase (IDO) activity and expression were increased after IFN-γ licensing in undifferentiated MSCs, they were reduced after differentiation. IFN-γ licensing to differentiated MSCs elevated the reduced IDO expression in differentiated MSCs; however, the increase was not sufficient to reach to the level achieved by undifferentiated MSCs. During a mixed lymphocyte reaction with quantification of TNF-α concentration, proliferation and activation of xenogeneic PBMCs were suppressed by undifferentiated MSCs but inhibited to a lesser extent by differentiated MSCs. IFN-γ licensing increasingly suppressed proliferation of PBMCs in undifferentiated MSCs but it was incapable of elevating the reduced immunosuppressive ability of differentiated MSCs. Migratory ability through a scratch assay and gene expression study was reduced in differentiated MSCs than their undifferentiated counterparts; IFN-γ licensing was unable to enhance the reduced migratory ability in differentiated MSCs. Similar results were found in a Transwell system with differentiated MSCs in the upper chamber toward xenogeneic PBMCs in the lower chamber, despite IFN-γ licensing increased the migratory ability of undifferentiated MSCs. Overall, IFN-γ licensing did not enhance the reduced immunomodulatory and migratory properties of differentiated MSCs in a xenogeneic application. This study provides a better understanding of the ways in which MSC therapy can be applied.


Assuntos
Interferon gama/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Xenoenxertos/metabolismo , Humanos , Imunomodulação/efeitos dos fármacos , Interferon gama/fisiologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/metabolismo
18.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502071

RESUMO

We evaluated the role of allicin in periodontitis using an in silico and in vitro design. An in silico docking analysis was performed to assess the plausible interactions between allicin and PD-L1. The cytokine profile of gingival crevicular fluid (GCF) samples obtained from periodontitis patients was estimated by cytometric bead array. CD3+ lymphocytes isolated from the peripheral blood were sorted and characterized using immunomagnetic techniques. Cultured and expanded lymphocytes were treated with the GCF samples to induce T-cell exhaustion. Optimum concentrations of allicin were added to exhausted lymphocytes to compare the expression of TIM-3 and LAG-3 gene expression at baseline and post-treatment. Allicin was found to bind to the PD-L1 molecule as revealed by the in-silico experiment, which is possibly an inhibitory interaction although not proven. GCF from periodontitis patients had significantly higher concentrations of TNF-α, CCL2, IL-6, IFN-γ, and CXCL8 than controls. GCF treatment of CD3+ lymphocytes from the periodontitis patients significantly increased expression of T-cell exhaustion markers TIM-3 and LAG-3. Allicin administration with GCF treatment resulted in significant lowering of the expression of exhaustion markers. Allicin may exert an immunostimulatory role and reverse immune-destructive mechanisms such as T-cell exhaustion.


Assuntos
Antígeno B7-H1/metabolismo , Dissulfetos/farmacologia , Periodontite/metabolismo , Ácidos Sulfínicos/farmacologia , Linfócitos T/efeitos dos fármacos , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno B7-H1/química , Sítios de Ligação , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL6/genética , Quimiocina CXCL6/metabolismo , Dissulfetos/química , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ligação Proteica , Ácidos Sulfínicos/química , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
19.
Int Heart J ; 62(5): 1096-1105, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544982

RESUMO

While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis (CS), treatment regimens have consisted of generalized heart failure therapies and non-specific anti-inflammatory regimens. The overall goal of this study was to perform high-sensitivity plasma profiling of specific inflammatory pathways in patients with sarcoidosis and with CS.Specific inflammatory/proteolytic cascades were upregulated in sarcoidosis patients, and certain profiles emerged for CS patients.Plasma samples were collected from patients with biopsy-confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose positron emission tomography (n = 47) and compared to those of referent control subjects (n = 6). Using a high-sensitivity, automated multiplex array, cytokines, soluble cytokine receptor profiles (an index of cytokine activation), as well as matrix metalloproteinase (MMP), and endogenous MMP inhibitors (TIMPs) were examined.The plasma tumor necrosis factor (TNF) and soluble TNF receptors sCD30 and sTNFRI were increased using sarcoidosis, and sTNFRII increased in CS patients (n = 18). The soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2 and sVEGFR3) increased to the greatest degree in CS patients. When computed as a function of referent control values, the majority of soluble cytokine receptors increased in both sarcoidosis and CS groups. Plasma MMP-9 levels increased in sarcoidosis but not in the CS subset. Plasma TIMP levels declined in both groups.The findings from this study were the identification of increased activation of a cluster of soluble cytokine receptors, which augment not only inflammatory cell maturation but also transmigration in patients with sarcoidosis and patients with cardiac involvement.


Assuntos
Citocinas/metabolismo , Cardiopatias/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Sarcoidose/diagnóstico , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Fluordesoxiglucose F18/administração & dosagem , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/patologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação/metabolismo , Masculino , Inibidores de Metaloproteinases de Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Receptores de Interleucina-2/metabolismo , Receptores do Fator de Necrose Tumoral/sangue , Medição de Risco , Sarcoidose/sangue , Sarcoidose/complicações , Sarcoidose/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Am J Case Rep ; 22: e932963, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564689

RESUMO

BACKGROUND Adalimumab is a biological anti-tumor necrosis factor (TNF) agent which induces and maintains remission in patients with moderate-to-severe Crohn disease (CD). An adverse effect of its use is reactivation of latent infections, such as tuberculosis (TB). TB is caused by Mycobacterium tuberculosis and continues to be an important public health problem in some developing countries, such as Brazil. The present report describes the case of a patient with CD who developed pulmonary TB while receiving adalimumab therapy. CASE REPORT A 38-year-old penitentiary worker presented with colonic CD that was intolerant to azathioprine and was started on adalimumab. After 3 months, he experienced coughing, fever, and weight loss, and was diagnosed with pulmonary TB. A chest X-ray and tuberculin skin test performed before he started taking adalimumab were negative for latent TB. The patient was treated for 9 months to cure his infection. The use of adalimumab was suspended while the TB was investigated and he took mesalazine to achieve clinical and endoscopic remission of CD. CONCLUSIONS Adequate screening and chemoprophylaxis for latent TB are indicated in patients at high risk of infection. In patients with inflammatory bowel disease, after anti-TNF therapy is started, strict monitoring is required so that opportunistic infections can be detected early and morbidity and mortality reduced in this population.


Assuntos
Doença de Crohn , Tuberculose Pulmonar , Adalimumab/efeitos adversos , Adulto , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab , Masculino , Tuberculose Pulmonar/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
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