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1.
Braz. J. Pharm. Sci. (Online) ; 58: e191132, 2022. tab, graf
Article in English | LILACS | ID: biblio-1394049

ABSTRACT

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination


Subject(s)
Animals , Male , Rats , Arthritis, Experimental/chemically induced , Therapeutic Uses , Enzyme-Linked Immunosorbent Assay/methods , Dinoprostone/adverse effects , Interleukin-6/pharmacology , Interleukin-1/pharmacology , Interleukin-10/pharmacology , Matrix Metalloproteinases , Microscopy, Electron, Transmission/methods
2.
Article in Chinese | WPRIM | ID: wpr-928733

ABSTRACT

OBJECTIVE@#To explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection.@*METHODS@#68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed.@*RESULTS@#The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05).@*CONCLUSION@#The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.


Subject(s)
Cytokines/metabolism , Humans , Interleukin-10 , Interleukin-6/metabolism , Leukemia/metabolism , Shock, Septic/metabolism , Th1 Cells/metabolism , Th2 Cells/metabolism , Tumor Necrosis Factor-alpha/metabolism
3.
Article in Chinese | WPRIM | ID: wpr-928319

ABSTRACT

OBJECTIVE@#To study the risk factors of stroke after of elderly patients with hip fracture after operation.@*METHODS@#From March 2012 to June 2017, 500 elderly patients with hip fracture who underwent hip replacement were selected, including 286 males and 214 females, aged from 60 to 76 years old with an average of (68.49±11.85) years. They were divided into stroke group with 30 cases and control group with 470 cases according to the occurrence of acute stroke within two weeks after operation. The general data and serum contents of cytokines IL-1, IL-6, IL-10 and TNF-α were compared between the two groups. The overall survival of the two groups were followed up.@*RESULTS@#There was no significant difference in sex, age, anesthesia method, operation time, intraoperative blood loss, preoperative IL-1, IL-6, IL-10 and TNF-α contenta between stroke group and control group(P>0.05). The prevalence of hypertension, diabetes mellitus, atrial fibrillation, intraoperative hypotension, IL-1, IL-6, IL-10 and TNF-α contenta 1 day and 3 days after operation of stroke group were significantly higher than control group(P<0.05);up to the date of follow-up, the cumulative survival rate of stroke patients were significantly lower than those of the control group(P<0.05). Logistic regression analysis showed that intraoperative hypotension, elevated contents of serum IL-1 and TNF-α at 1 and 3 days after operation were risk factors for acute stroke.@*CONCLUSION@#Postoperative stroke in elderly patients with hip fracture affects the prognosis of the disease. The increase of inflammatory cytokines IL-1 and TNF-α after operation is an independent risk factor for stroke.


Subject(s)
Aged , Cytokines , Female , Hip Fractures/surgery , Humans , Hypotension , Interleukin-1 , Interleukin-10 , Interleukin-6 , Male , Middle Aged , Risk Factors , Stroke/etiology , Tumor Necrosis Factor-alpha
4.
Article in Chinese | WPRIM | ID: wpr-928133

ABSTRACT

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.


Subject(s)
Animals , Berberine Alkaloids , Blood Glucose/metabolism , Diabetes Mellitus , Diabetic Neuropathies/genetics , Interleukin-10 , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Microglia , Neuralgia/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Spinal Cord/metabolism , Streptozocin/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
5.
Article in Chinese | WPRIM | ID: wpr-927397

ABSTRACT

OBJECTIVE@#To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD.@*METHODS@#A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus.@*RESULTS@#There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.


Subject(s)
Acupuncture Therapy , Animals , Dementia, Vascular/therapy , Interferon-gamma , Interleukin-10 , Interleukin-4 , Neuroinflammatory Diseases , Rats , Rats, Wistar , Th2 Cells , Tumor Necrosis Factor-alpha
6.
São Paulo; s.n; s.n; 2022. 62 p. graf.
Thesis in Portuguese | LILACS | ID: biblio-1378655

ABSTRACT

As Células-Tronco Mesenquimais (CTMs), são células multipotentes, presentes em diversos tecidos, sendo bastante estudada devido sua capacidade imunorregulatória por meio da liberação de fatores solúveis. Fatores estes que atuam sobre as funções de células do sistema imunitário. Simultaneamente, estudos indicam que os compostos flavonoides, em destaque a Delfinidina, presente em alguns frutos e flores, possuem atuação anti-inflamatória e inibitória sobre células do sistema imunitário. Todavia, são escassos os estudos em relação entre a capacidade imunorregulatória da CTM e a influência da Delfinidina, sendo este o objetivo deste estudo. Inicialmente, a Delfinidina 3-O-ß-D-glicosídeo foi escolhido, devido a sua maior estabilidade e a dose de 50 µM foi selecionada após análise por citometria de fluxo que mostrou aumento da fase proliferativa do ciclo celular. Posteriormente ao realizar análise da produção de fatores solúveis pelas CTM, os resultados mostraram aumento da produção de IL-10, TGF-ß e Oxido nítrico pelas CTM tratadas com Delfinidina. Bem como, diminuição da expressão de p-NF-κB/NF-κB pelas CTMs tratadas com Delfinidina, quando avaliadas por Wersten Blot. Adicionalmente, para analisar a Delfinidina sobre os efeitos imunorregulatórios da CTM sob macrófagos (RAW 264.7), célula esta, importante no sistema imune inato. Foram realizadas culturas condicionadas, com posterior análise da produção de fatores solúveis, os resultados mostraram aumento da produção de IL-10, e diminuição da produção de TNF-α, IL-1α e IL-12 pelos macrófagos, nas culturas condicionadas. Assim como, diminuição da expressão do fator p-NF-κB/NF-κB pelos macrófagos nas culturas condicionadas, quando avaliadas por Wersten Blot. Ademais, ao analisar a atividade metabólica dos macrófagos por ensaio de MTT, os resultados mostraram que as culturas condicionadas e a Delfinidina per si foi capaz de diminuir a atividade metabólica, sem alterar os efeitos anti-inflamatórios sobre a célula. Em síntese, a Delfinidina mostrou acentuar a atuação imunorregulatória da CTM sobre a linhagem macrofágica, célula esta, de grande importância para o sistema imune inato


Mesenchymal Stem Cells (MSCs) are multipotent cells present in various tissues, being widely studied due to their immunoregulatory capacity through the release of soluble factors. These factors act on the functions of cells of the immune system. Simultaneously, studies indicate that flavonoid compounds, especially Delphinidin, present in some fruits and flowers, have anti inflammatory and inhibitory effects on immune system cells. However, there are few studies on the relationship between the immunoregulatory capacity of MSC and the influence of Delphinidin, which is the objective of this study. Initially, Delphinidin 3-O-ß-D-glycoside was chosen due to its greater stability and the 50 µM dose was selected after analysis by flow cytometry which showed an increase in the proliferative phase of the cell cycle. Subsequently, when analyzing the production of soluble factors by MSCs, the results showed an increase in the production of IL-10, TGF-ß and nitric oxide by MSCs treated with Delphinidin. As well as decreased expression of p-NF-κB/NF-κB by MSCs treated with Delphinidin, when evaluated by Wersten Blot. Additionally, to analyze Delphinidin on the immunoregulatory effects of MSC on macrophages (RAW 264.7), this cell is important in the innate immune system. Conditioned cultures were performed, with subsequent analysis of the production of soluble factors, the results showed an increase in the production of IL-10, and a decrease in the production of TNF-α, IL-1α and IL-12 by macrophages, in the conditioned cultures. As well as decreased expression of p-NF-κB/NF-κB factor by macrophages in conditioned cultures, when evaluated by Wersten Blot. Furthermore, when analyzing the metabolic activity of macrophages by MTT assay, the results showed that conditioned cultures and Delphinidin itself was able to decrease the metabolic activity, without altering the anti-inflammatory effects on the cell. In summary, Delphinidin has shown to enhance the immunoregulatory action of MSC on the macrophage lineage, a cell that is of great importance for the innate immune system


Subject(s)
Flavonoids/analysis , Immune System , Transforming Growth Factors , Interleukin-1/adverse effects , Interleukin-10/adverse effects , Mesenchymal Stem Cells/classification , Flow Cytometry/instrumentation , Anti-Inflammatory Agents/administration & dosage
7.
Article in Chinese | WPRIM | ID: wpr-936334

ABSTRACT

OBJECTIVE@#To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.@*METHODS@#Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 μ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-β, IL-6, IL-10 and TNF-α were detected with RT-PCR.@*RESULTS@#Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-β (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 μ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-β (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist.@*CONCLUSION@#Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.


Subject(s)
Animals , Cell Differentiation/drug effects , Endoribonucleases/metabolism , Estradiol/pharmacology , Estrogens/metabolism , Interleukin-10 , Interleukin-6/metabolism , Macrophages, Peritoneal/metabolism , Mice , Phenotype , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effects , X-Box Binding Protein 1/metabolism
8.
Article in English | WPRIM | ID: wpr-929025

ABSTRACT

OBJECTIVES@#Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation.@*METHODS@#This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation.@*RESULTS@#Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05).@*CONCLUSIONS@#Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.


Subject(s)
Aged , Aged, 80 and over , Bradycardia , Cognitive Dysfunction/prevention & control , Delirium/prevention & control , Dexmedetomidine/therapeutic use , Humans , Hypotension/drug therapy , Interleukin-10 , Middle Aged , Postoperative Cognitive Complications/prevention & control , Postoperative Complications/epidemiology , Prospective Studies , Tumor Necrosis Factor-alpha
9.
Article in English | WPRIM | ID: wpr-929021

ABSTRACT

OBJECTIVES@#Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint destruction. Both inflammatory response and oxidative stress contribute to the pathogenesis of RA. Oxidative damage can induce and aggravate the imbalance of immune inflammation and promote cell and tissue damage. In this study, the expression of long non-coding RNA (lncRNA) LINC00638 in peripheral blood of patients with RA damp-heat arthralgia syndrome was observed, and the correlation between LINC00638 and disease activity, immune inflammation and oxidative stress indicator was investigated. Subsequently, the mechanisms for LINC00638 in regulating the inflammatory response and oxidative stress in RA fibroblast-like synoviocyte (FLS) under the condition of overexpression and interference were further explored.@*METHODS@#In this study, 48 RA patients with damp-heat arthralgia syndrome and 27 normal healthy subjects, who came from Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, were included; and they were divided into a RA group and a control group. The expression of LINC00638 in peripheral blood mononuclear cells (PBMC) from the subjects was detected by real-time PCR. Enzyme linked immunosorbent assay (ELISA) was used to detect serum interleukin (IL)-10, IL-17, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2) expression. Spearman method was used to study the relationship between LINC00638 and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), and to observe the relation between LINC00638 and the Disease Activity Score of 28 Joint (DAS28), Quantitative Score of Damp Heat Syndrome, Visual Analogue Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). RA-FLS was induced by RA-PBMC, and the RA in vitro cell experimental model was established. LINC00638 overexpression plasmid and small interfering RNA (siRNA) were constructed and transfected into RA-FLS. The cell experiments were divided into 4 groups: a pcDNA3. 1- control group, a pcDNA3.1-LINC00638 group, a siRNA-control group, and a siRNA-LINC00638 group. The transfection efficiency of overexpression plasmid and siRNA was detected by real-time PCR, the expression of TNF-α and IL-10 was detected by ELISA, and the expression of antioxidant proteins HO-1 and SOD2 was detected by immunofluorescence.@*RESULTS@#Compared with the control group, the expression of LINC00638 in the RA group was lower (P<0.01). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of LINC00638 was 0.9271. The DAS28 in RA group was 5.70 (5.40-6.50), the Quantitative Score of Damp-heat Syndrome was 20.0 (17.0-23.0), and the VAS score was 7.0 (6.3-8.0). Compared with the control group, the ESR, CRP, RF, anti-CCP, SAS and SDS scores in the RA group were significantly increased (all P<0.01). Spearman correlation analysis showed that: LINC00638 was negatively correlated with ESR (r=-0.532, P<0.01), CRP (r=-0.367, P<0.05), TNF-α (r=-0.375, P<0.01), MDA (r= -0.295, P<0.05), DAS28 (r=-0.450, P<0.01), and which was positively correlated with SOD2 (r=0.370, P<0.05). After the induction of RA-FLS, the expression level of LINC00638 was significantly decreased (P<0.01), indicating that the stimulation of PBMC could effectively reduce the expression of LINC00638 in RA-FLS, so the experimental model of RA-FLS-induced by PBMC was utilized. Compared with the pcDNA3.1-control group, the expressions of LINC00638, IL-10, SOD2, and HO-1 in the pcDNA3.1-LINC00638 group were significantly increased (all P<0.01), and the expression of TNF-α was decreased (P<0.01). Compared with siRNA-control group, LINC00638, IL-10, SOD2 and HO-1 in the siRNA-LINC00638 group were significantly decreased (all P<0.01), and TNF-α was significantly increased (P<0.01).@*CONCLUSIONS@#LINC00638 is down-regulated in the peripheral blood of RA patients with damp-heat arthralgia syndrome, which is correlated with disease activity, immune inflammation and oxidative stress. Overexpression of LINC00638 can down-regulate pro-inflammatory factors, up-regulate anti-inflammatory factors, and increase antioxidant enzyme activity, thereby improving inflammation and oxidative stress in RA. LINC00638 is the differential lncRNA obtained by the research group's previous high-throughput sequencing of the whole transcriptome of peripheral blood PBMCs in RA patients and validation of clinical samples. In order to deepen the molecular biology research of this gene, the microRNA and mRNA targeted by LINC00638 can be further studied from the perspective of competing endogenous RNAs.


Subject(s)
Anti-Citrullinated Protein Antibodies/metabolism , Antioxidants , Arthralgia/metabolism , Arthritis, Rheumatoid , C-Reactive Protein , Hot Temperature , Humans , Inflammation/genetics , Interleukin-10/metabolism , Leukocytes, Mononuclear , Oxidative Stress , RNA, Long Noncoding/metabolism , RNA, Small Interfering , Tumor Necrosis Factor-alpha/metabolism
10.
Article in English | WPRIM | ID: wpr-928963

ABSTRACT

OBJECTIVE@#To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD).@*METHODS@#After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated.@*RESULTS@#After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05).@*CONCLUSION@#The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.


Subject(s)
Adiponectin , Animals , Cytokines , Diet, High-Fat , Glucose , Insulin Resistance , Interleukin-10 , Liver , Male , Minerals , Non-alcoholic Fatty Liver Disease/pathology , Pioglitazone/therapeutic use , Rats , Rats, Wistar , Resins, Plant , Resistin/therapeutic use , Tumor Necrosis Factor-alpha
11.
Chinese Journal of Stomatology ; (12): 390-396, 2022.
Article in Chinese | WPRIM | ID: wpr-935878

ABSTRACT

Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.


Subject(s)
Cell Polarity , Humans , Interleukin-10/metabolism , Lipopolysaccharides/pharmacology , Macrophage Activation , Macrophages/drug effects , MicroRNAs/metabolism , NF-kappa B/metabolism , Porphyromonas gingivalis , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/metabolism
12.
Article in Chinese | WPRIM | ID: wpr-941030

ABSTRACT

OBJECTIVE@#To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity.@*METHODS@#Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed.@*RESULTS@#The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae.@*CONCLUSION@#E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.


Subject(s)
Animals , Colitis, Ulcerative/drug therapy , Colon/metabolism , Interleukin-10 , Interleukin-12/therapeutic use , Male , RNA, Messenger/metabolism , Rats , Rats, Wistar , Toll-Like Receptor 2/metabolism
13.
Article in Chinese | WPRIM | ID: wpr-941010

ABSTRACT

OBJECTIVE@#To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.@*METHODS@#Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.@*RESULTS@#Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).@*CONCLUSION@#Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.


Subject(s)
Animals , Cytokines , Dexamethasone , Heart Injuries , Interleukin-10 , Interleukin-6 , Larva , Male , Mice , Mice, Inbred BALB C , Myocardium , Sepsis , Transforming Growth Factor beta , Trichinella spiralis , Tumor Necrosis Factor-alpha
14.
Journal of Integrative Medicine ; (12): 453-462, 2022.
Article in English | WPRIM | ID: wpr-939897

ABSTRACT

OBJECTIVE@#Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.@*METHODS@#A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.@*RESULTS@#It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.@*CONCLUSION@#Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.


Subject(s)
Animals , Arthritis, Experimental/therapy , Arthritis, Rheumatoid/therapy , Cytokines , Disease Models, Animal , Interleukin-10 , Interleukin-17 , Interleukin-6 , Male , Mice , Mice, Inbred DBA , MicroRNAs/genetics , Moxibustion , T-Lymphocytes, Regulatory , Th17 Cells/pathology , Tumor Necrosis Factor-alpha
15.
Journal of Integrative Medicine ; (12): 348-354, 2022.
Article in English | WPRIM | ID: wpr-939896

ABSTRACT

OBJECTIVE@#Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.@*METHODS@#In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5'-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.@*RESULTS@#Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.@*CONCLUSION@#This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Apoptosis , Biomarkers , Cyclophosphamide , Inflammation/drug therapy , Interleukin-10 , Interleukin-6/metabolism , Liver , Male , NF-kappa B/metabolism , Oxidative Stress , Rats , Salvadoraceae/metabolism , Tumor Necrosis Factor-alpha/metabolism
16.
Article in Chinese | WPRIM | ID: wpr-939508

ABSTRACT

OBJECTIVE@#To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA).@*METHODS@#A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method.@*RESULTS@#Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group.@*CONCLUSION@#Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.


Subject(s)
Acupuncture Therapy , Animals , Arthritis, Experimental/therapy , Cartilage, Articular , Chromatin , Hyperplasia , Interleukin-10 , Interleukin-4 , Male , Matrix Metalloproteinase 3 , Matrix Metalloproteinase 9 , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/genetics
17.
Braz. j. oral sci ; 20: e211654, jan.-dez. 2021. ilus
Article in English | LILACS, BBO | ID: biblio-1254524

ABSTRACT

Grade C periodontitis in youngers is characterized by a severe form of periodontitis, and IL10 rs6667202 single nucleotide polymorphism (SNP) has been described as an important feature in this disease etiology. Aim: This study aimed to evaluate, in vivo, the functionality of IL10 rs6667202 SNP on IL-10 gingival fluid levels. Methods: Thirty patients with Perio4C were selected, 15 with the IL10 AA genotype (rs6667202) and 15 with AC/CC genotypes. The gingival fluid was collected from two sites with probing depth ≥ 7 mm and bleeding on probing, and two healthy sites. The IL-10 concentration was determined by Luminex/MAGpix platform. Results: In deep pockets, the IL10 AA genotype presented a lower concentration of IL-10 when compared with AC or CC genotypes (p<0.05). In shallow pockets, no difference between groups was seen (p>0.05). Conclusion: IL10 rs6667202 SNP decreases the production of IL-10 in crevicular fluid, potentially affecting this disease progression


Subject(s)
Humans , Male , Female , Aggressive Periodontitis , Interleukin-10 , Polymorphism, Single Nucleotide
18.
J. pediatr. (Rio J.) ; 97(5): 546-551, Sept.-Oct. 2021. tab, graf
Article in English | LILACS | ID: biblio-1340156

ABSTRACT

Abstract Objective: The aim of this study was to evaluate the association between possible functional interleukin-10 (IL-10) polymorphisms, IL-10 expression and regulatory T cells (Tregs) frequency, and/or asthma severity in a sample of children and adolescents. Methods: This is a nested case-control genetic association study. The study sample consisted of children and adolescents aged 8-14 from public schools. Four polymorphisms of the IL-10 gene (rs1518111, rs3024490, rs3024496, rs3024491) were genotyped in asthmatic subjects and controls using real-time PCR. Tregs cells and IL-10 were analyzed in peripheral blood mononuclear cells by flow cytometry. The severity of asthma was defined according to the Global Initiative for Asthma (GINA) guideline. Results: One hundred twenty-three asthmatic subjects and fifty-eight controls participated in the study. The single nucleotide polymorphism (SNP) rs3024491 (T allele) showed association with asthma severity, presenting a higher frequency in patients in the moderate asthma group. The T allele of variant rs3024491 also showed an association with reduced IL-10 levels (p = 0.01) and with increased Tregs frequency (p = 0.01). The other variants did not present consistent associations. Conclusions: Our results suggest that moderate asthma is associated with a higher frequency of the T allele in the SNP rs3024491. In addition, the variant rs3024491 (TT) was associated with a reduction in IL-10 production and an increased percentage of Tregs cells, suggesting possible mechanisms that influence asthma severity.


Subject(s)
Humans , Child , Adolescent , Asthma/genetics , Interleukin-10/genetics , Leukocytes, Mononuclear , Polymorphism, Single Nucleotide/genetics , Forkhead Transcription Factors , Interleukin-2 Receptor alpha Subunit
19.
Clin. biomed. res ; 41(3): 205-211, 20210000. tab, graf
Article in English | LILACS | ID: biblio-1343958

ABSTRACT

Introduction: Renal cell carcinoma (RCC) is one of the most prevalent kidney tumors. Inflammation is believed to be a key factor in its progression and spread since inflammatory markers are generally associated with poor prognosis in RCC patients. Cytokines are cell communication molecules involved in both healthy and pathological processes, including tumor growth and progression. Recent findings suggest that cytokine level measurements could be used for cancer monitoring and prognosis. Methods: This study characterized and compared the levels of different cytokines associated with the classical Th1, Th2, and Th17 immune responses in plasma samples from RCC patients (n = 25) and healthy controls (n = 29). Cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A) were evaluated by flow cytometry using a BD Cytometric Bead Array (CBA) kit. Results: No statistical differences in systemic IL-2, IL-4, IL-10, IL-17A, TNF, and INF-γ levels were observed between RCC patients and controls (p > 0.05). However, higher systemic IL-6 levels were observed in RCC patients (p = 0.0034). Conclusions: This study highlights the importance of assessing the impact of IL-6 on RCC pathogenesis and its potential role as a biomarker of disease progression. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Carcinoma, Renal Cell , Interleukin-6 , Interleukin-10 , Cytokinins/analysis , Inflammation
20.
Ciencia Tecnología y Salud ; 8(2): 166-183, 2021. il 27 c
Article in Spanish | LILACS, LIGCSA, DIGIUSAC | ID: biblio-1353093

ABSTRACT

El cáncer gástrico (CG) es la neoplasia del tubo digestivo más prevalente en el mundo, asociada a factores genéticos del hospedero y externos, como infección por Helicobacter pylori. La patogénesis incluye inflamación crónica mediada por citocinas del microambiente tumoral, detectables sistémicamente. Estudios previos reportan niveles séricos de citocinas y su contribución al diagnóstico de CG. El presente estudio analiza el perfil de citocinas del tipo de Th1(IFNγ), Th2(IL-4 e IL-10), Th17(Th-17A) y otras pro inflamatorias: IL-1ß, IL-6 y TNF-α, en plasma de 70 casos de pacientes con CG comparándolos con 132 sujetos sanos equiparables en edad y sexo. Los casos provinieron del Hospital Roosevelt e Instituto Nacional de Cancerología de Guatemala (Incan) y formaron parte de un estudio previo. Se analizó la base de datos clínicos, patológicos y epidemiológicos. Se midieron los niveles de citocinas utilizando el sistema "MSD MULTI-SPOT Assay System". La edad promedio de los casos fue 59.5 años, (DE 13.0), 51%, eran positivos para IgG anti H. pylori. Un 71% presentó adenocarcinoma grado III (Borrman), según clasificación de Lauren 55% tenían tipo intestinal. Las siete citocinas cuantificadas se encontraron significativamente elevadas (p < .05) en el plasma de los casos respecto a sus controles. Los casos de CG tipo difuso presentaron niveles de IFNγ significativa-mente elevados. Por regresión logística, las citocinas IL-6 e IL-10, están asociadas significativamente a CG (p < .05) independientemente del estatus de infección por H. pylori. Se destacan la IL-6 e IL-10 como las principales citocinas asociadas a la presencia de CG.


Gastric cancer (GC) is the most prevalent gastrointestinal neoplasm in the world, associated with host and external genetic factors, such as Helicobacter pylori infection. The pathogenesis includes chronic inflammation mediated by cytokines of the tumor microenvironment, systemically detectable. Previous studies report serum levels of cyto-kines and their contribution to the diagnosis of GC. The present study analyzes the profile of cytokines of the type Th1 (IFNγ), Th2 (IL-4 and IL-10), Th17 (Th-17A) and other pro-inflammatory: IL-1ß, IL-6 and TNF-α, in plasma of 70 cases of patients with GC compared with 132 healthy subjects comparable in age and sex. The cases came from the Roosevelt Hospital and the National Cancer Institute of Guatemala -Incan- and were part of a previous study. The clinical, pathological and epidemiological databases were analyzed. Cytokine levels were measured using the "MSD MULTI-SPOT Assay System". The average age of the cases was 59.5 years, (SD 13.0), 51% were positive for IgG anti H. pylori, 71% had grade III adenocarcinoma (Borrman), according to Laurenís classification, 55% had intestinal type. The seven cytokines quantified were found to be significantly elevated (p < .05) in the plasma of the cases compared to their controls. The diffuse GC cases presented significantly elevated IFNγ levels. By logistic regression, the cytokines IL-6 and IL-10 are significantly associated with GC (p < .05) regardless of the H. pylori infection status. IL-6 and IL-10 stand out as the main cytokines associated with the presence of GC.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Plasma/chemistry , Stomach Neoplasms/complications , Cytokines/analysis , Interleukin-6/analysis , Interleukin-1/analysis , Interleukin-10/analysis , Th2 Cells , Th17 Cells , Immunoglobulin G/analysis , Adenocarcinoma/complications , Biomarkers, Tumor/analysis , Helicobacter Infections/complications , Th1 Cells , Gastrointestinal Tract/pathology , Tumor Microenvironment , Neoplasms/complications
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