Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 154
Filter
1.
Article in Chinese | WPRIM | ID: wpr-879445

ABSTRACT

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


Subject(s)
Humans , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration , Intervertebral Disc Displacement/genetics , Nucleus Pulposus , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Tumor Necrosis Factor-alpha/metabolism
2.
J. appl. oral sci ; 28: e20200033, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1134805

ABSTRACT

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


Subject(s)
Animals , Male , Rats , Root Canal Filling Materials , Tumor Necrosis Factor-alpha/metabolism , Dental Cements , Interleukin-1beta/metabolism , Biomineralization , Oxides , Biocompatible Materials , Rats, Wistar , Silicates , Calcium Compounds , Aluminum Compounds , Subcutaneous Tissue , Drug Combinations , Inflammation
3.
Braz. j. med. biol. res ; 52(9): e8525, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011614

ABSTRACT

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1β, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1β by suppressing the increase in IL-1β, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1β-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1β to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Chondrocytes/drug effects , Ginsenosides/pharmacology , Interleukin-1beta/drug effects , Interleukin-1 Receptor Accessory Protein/metabolism , Intervertebral Disc Degeneration/metabolism , Dinoprostone/metabolism , Cell Survival/drug effects , Tumor Necrosis Factor-alpha/metabolism , Low Back Pain/metabolism , Nitric Oxide Synthase/metabolism , Chondrocytes/cytology , Chondrocytes/metabolism , Ginsenosides/metabolism , Cyclooxygenase 2/metabolism , Aggrecans/metabolism , Interleukin-1beta/metabolism , Ubiquitination , Nucleus Pulposus/cytology , Nucleus Pulposus/drug effects , Nucleus Pulposus/metabolism , Inflammation/metabolism
4.
Acta cir. bras ; 34(6): e201900609, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019266

ABSTRACT

Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.


Subject(s)
Animals , Male , Rats , Pancreatitis, Acute Necrotizing/complications , Acute Lung Injury/prevention & control , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Phosphorylation , Immunohistochemistry , Signal Transduction , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Rats, Wistar , Pancreatitis, Acute Necrotizing/pathology , Disease Models, Animal , Interleukin-1beta/metabolism , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology
5.
Clinics ; 74: e981, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011918

ABSTRACT

OBJECTIVE: Muscle wasting contributes to the reduced quality of life and increased mortality in chronic obstructive pulmonary disease (COPD). Muscle atrophy in mice with cachexia was caused by Activin A binding to ActRIIB. The role of circulating Activin A leading to muscle atrophy in COPD remains elusive. METHODS: In the present study, we evaluated the relationship between serum levels of Activin A and skeletal muscle wasting in COPD patients. The expression levels of serum Activin A were measured in 78 stable COPD patients and in 60 healthy controls via ELISA, which was also used to determine the expression of circulating TNF-α levels. Total skeletal muscle mass (SMM) was calculated according to a validated formula by age and anthropometric measurements. The fat-free mass index (FFMI) was determined as the fat-free mass (FFM) corrected for body surface area. RESULTS: Compared to the healthy controls, COPD patients had upregulated Activin A expression. The elevated levels of Activin A were correlated with TNF-α expression, while total SMM and FFMI were significantly decreased in COPD patients. Furthermore, serum Activin A expression in COPD patients was negatively associated with both FFMI and BMI. CONCLUSION: The above results showed an association between increased circulating Activin A in COPD patients and the presence of muscle atrophy. Given our previous knowledge, we speculate that Activin A contributes to skeletal muscle wasting in COPD.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Muscular Atrophy/etiology , Pulmonary Disease, Chronic Obstructive/complications , Activins/blood , Cachexia/metabolism , Muscular Atrophy/metabolism , Muscular Atrophy/blood , Body Mass Index , Case-Control Studies , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Muscle, Skeletal/physiopathology , Pulmonary Disease, Chronic Obstructive/blood , Activins/metabolism , Inhibin-beta Subunits
6.
Acta cir. bras ; 33(8): 723-735, Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-949372

ABSTRACT

Abstract It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.


Subject(s)
Humans , Reperfusion Injury/physiopathology , Reperfusion Injury/therapy , Ischemic Preconditioning/methods , Ischemia/physiopathology , Ischemia/therapy , Liver/blood supply , Time Factors , Mitochondria, Liver/metabolism , Reperfusion Injury/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cell Death/physiology , Oxidative Stress/physiology , Matrix Metalloproteinases/metabolism , Ischemia/metabolism , Nitric Oxide/metabolism
7.
Int. j. morphol ; 36(2): 488-492, jun. 2018. tab, graf
Article in English | LILACS | ID: biblio-954142

ABSTRACT

Spinal cord injury causes neuron nerve fiber loss. The aim of this study was to investigate the neuroprotective, inflammatory and angiogenetic effects of melatonin on rat spinal cord injury (SCI). For spinal cord injury, a standard weight reduction method was used that caused moderate severity of injury (100 g / cm force) at T10 Melatonin (10 mg/kg intraperitoneally ) was administered for 10 days after trauma. Each group consisted of 10 animals. of these, six were used for biochemical and four were used for the evaluation of histological analysis. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity. Spinal cord injury and melatonin treated group were compared. Melatonin administration in spinal cord injury increased the activity of glial cells in the radial and funicular cells and ependymal cells and increased the activity of glial cells and also showed a positive effect on inflammation and vascular endothelial cells in synaptic connections in the nerve fibers undergoing spinal injury endothelial degeneration It is thought that it can regulate the degenerative effect which is caused by both the inflammatory effect and the angiogenic effect which will have a positive effect on the neural connection.


La lesión de la médula espinal (SCI) provoca daño en la fibra nerviosa, que puede conducir a alteraciones motoras y sensitivas, incluso la muerte. El objetivo de este estudio fue investigar los efectos neuroprotectores, proinflamatorios y proangiogénicos de la melatonina en un modelo de SCI inducida en rata. Para tal efecto se utilizaron dos grupos: Grupo 1 (n:10) se le indujo una SCI, mediante el método de reducción de peso estándar (100 g/cm fuerza), provocando una lesión de severidad moderada. Grupo 2 (n:10) inducción SCI más aplicación de T10 Melatonina (10 mg / kg v.i.) durante 10 días después del trauma. Muestras de seis animales de cada grupo fueron usados para análisis bioquímicos y los otros cuatro para la evaluación histológica. Se tomaron muestras de médula espinal para el examen histológico y para la determinación de niveles de malondialdehído (MDA) y glutatión (GSH), actividad mieloperoxidasa (MPO) y se comparó la lesión de la médula espinal y el grupo tratado con melatonina. La administración de melatonina en la lesión de la médula espinal aumentó la actividad de las células gliales en las células radiales, funiculares y ependimocitos. Ademas mostró un efecto positivo sobre la inflamación y angiogénesis en las conexiones sinápticas en las fibras nerviosas sometidas a lesión espinal. Pudiendo este participar en la regulación del efecto degenerativo causado, principalmente, por acción de angiogénesis e inflamación local.


Subject(s)
Spinal Cord Injuries/metabolism , Spinal Cord Injuries/drug therapy , Melatonin/metabolism , Melatonin/therapeutic use , Immunohistochemistry , Tumor Necrosis Factor-alpha/metabolism , Endothelin-1/metabolism
8.
Acta cir. bras ; 33(6): 483-490, June 2018. tab, graf
Article in English | LILACS | ID: biblio-949354

ABSTRACT

Abstract Purpose: To evaluate the effects of hypothermia treatment on meconium-induced inflammation. Methods: Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. Results: The BAL fluid TNF-α, IL-1β, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). Conclusion: Meconium-induced inflammatory cytokine production is affected by the body temperature control.


Subject(s)
Animals , Male , Pneumonia/pathology , Meconium Aspiration Syndrome/pathology , Meconium Aspiration Syndrome/therapy , Hypothermia, Induced/methods , Pneumonia/metabolism , Pneumonia/therapy , Enzyme-Linked Immunosorbent Assay , Bronchoalveolar Lavage Fluid/chemistry , Meconium Aspiration Syndrome/metabolism , Reproducibility of Results , Interleukin-8/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Treatment Outcome , Rats, Wistar , Disease Models, Animal , Interleukin-1beta/metabolism , Luminescent Measurements/methods , Lung/pathology
9.
Braz. j. med. biol. res ; 51(8): e6896, 2018. graf
Article in English | LILACS | ID: biblio-951743

ABSTRACT

Excessive exposure to ultraviolet (UV) rays can cause damage of the skin and may induce cancer, immunosuppression, photoaging, and inflammation. The long non-coding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) is involved in multiple human biological processes. However, its role in UVB-induced keratinocyte injury is unclear. This study was performed to investigate the effects of HOTAIR in UVB-induced apoptosis and inflammatory injury in human keratinocytes (HaCaT cells). Quantitative real-time polymerase chain reaction was performed to analyze the expression levels of HOTAIR, PKR, TNF-α, and IL-6. Cell viability was measured using trypan blue exclusion method and cell apoptosis using flow cytometry and western blot. ELISA was used to measure the concentrations of TNF-α and IL-6. Western blot was used to measure the expression of PKR, apoptosis-related proteins, and PI3K/AKT and NF-κB pathway proteins. UVB induced HaCaT cell injury by inhibiting cell viability and promoting cell apoptosis and expressions of IL-6 and TNF-α. UVB also promoted the expression of HOTAIR. HOTAIR suppression increased cell viability and decreased apoptosis and expression of inflammatory factors in UVB-treated cells. HOTAIR also promoted the expression of PKR. Overexpression of HOTAIR decreased cell viability and increased cell apoptosis and expression of inflammatory factors in UVB-treated cells by upregulating PKR. Overexpression of PKR decreased cell viability and promoted cell apoptosis in UVB-treated cells. Overexpression of PKR activated PI3K/AKT and NF-κB pathways. Our findings identified an essential role of HOTAIR in promoting UVB-induced apoptosis and inflammatory injury by up-regulating PKR in keratinocytes.


Subject(s)
Humans , Keratinocytes/metabolism , Apoptosis/physiology , eIF-2 Kinase/metabolism , Apoptosis Inducing Factor/metabolism , RNA, Long Noncoding/metabolism , Ultraviolet Rays/adverse effects , Gene Expression , Keratinocytes/radiation effects , Up-Regulation , Cell Survival/physiology , NF-kappa B/drug effects , NF-kappa B/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Apoptosis/radiation effects , Phosphatidylinositol 3-Kinases/metabolism , Inflammation/etiology
10.
Int. j. morphol ; 35(2): 723-732, June 2017. ilus
Article in English | LILACS | ID: biblio-893046

ABSTRACT

Tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6, are prominent mediators of inflammation and have been confirmed to be elevated in at least a subgroup of women with polycystic ovary syndrome (PCOS). In this study, the effects of Silymarin (SLM) on the expression TNF-a, IL-6, CRP and symptoms of PCOS were studied. In this research, PCOS was induced by injection of Estradiol Valerate. PCOS rats were divided into control and experimental groups received intraperitoneal injection SLM extract daily. After syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 was detected by the ELISA kit. The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. It can be concluded that having anti-inflammatory substances, Silymarin is effective in symptoms of this syndrome and metabolic syndrome.


El factor de necrosis tumoral alfa (TNF-a) y la interleucina (IL) -6 son mediadores prominentes de la inflamación y se ha confirmado que están elevados en al menos un subgrupo de mujeres con síndrome de ovario poliquístico (SOP). En este estudio se estudiaron los efectos de Silymarin (SLM) en la expresión TNF-a, IL-6, PCR y síntomas de SOP. El SOP fue inducido por inyección de valerato de estradiol. Las ratas SOP se dividieron en grupos control y los grupos experimentales recibieron diariamente un extracto de SLM por inyección intraperitoneal. Después de la inducción del síndrome, los ovarios se analizaron mediante histología e inmunohistoquímica. Se detectó IL-6 en suero mediante el kit ELISA. Los resultados indicaron una reducción significativa en los marcadores inflamatorios y cambios significativos en el espesor de las capas foliculares en el grupo de tratamiento en comparación con el control. Se puede concluir que con sustancias anti-inflamatorias, Silymarin es eficaz en los síntomas de este síndrome y el síndrome metabólico.


Subject(s)
Animals , Female , Rats , Anti-Inflammatory Agents/pharmacology , Polycystic Ovary Syndrome/metabolism , Silymarin/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Immunohistochemistry , Inflammation , Interleukin-6/metabolism , Rats, Wistar , Tumor Necrosis Factor-alpha/drug effects
11.
Braz. dent. j ; 28(3): 281-286, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-888657

ABSTRACT

Abstract The aim of this study was to find the role of TLR2 signaling pathway in reducing osteoclast activity and promoting osteoblast growth by inducing a combination of Aloe vera and cancellous bovine xenograft (XCB) into dental extraction socket. Forty-eight Cavia cobayas were used. They were divided into eight groups (n=6). For control group, their mandibular incisors were extracted and filled with PEG. For treatment groups, they were extracted and filled with XCB, Aloe vera and the combination of Aloe vera and XCB. The first four groups were sacrificed after 7 days and the other groups after 30 days. Immunohistochemistry and histopathology examination were conducted to examine TLR2, TNFa, OPG, collagen-1, and the osteoblast and osteoclast expressions. The expressions of TLR2, OPG and Collagen-1, as well as the number of osteoblast were increased. Meanwhile, the expressions of TNFa and osteoclast were decreased. The study finding was that TLR2 signaling pathway influenced alveolar bone osteogenesis process by reducing osteoclast activity and stimulating osteoblast growth induced by the combination of Aloe vera and XCB.


Resumo O objetivo deste estudo foi investigar o papel da via de sinalização de TLR2 na redução da atividade osteoclástica e na promoção do crescimento de osteoblastos, induzindo uma combinação de Aloe vera e enxerto de osso esponjoso bovino (EOEB) em alvéolo de extração dentária. Quarenta e oito Cavia cobayas foram utilizados e divididos em 8 grupos (n = 6). Para o grupo de controle, seus incisivos mandibulares foram extraídos e preenchidos com polietilenoglicol (PEG). Para grupos de tratamento, os dentes foram extraídos e preenchidos com EOEB, Aloe vera e a combinação de Aloe vera e EOEB. Os primeiros quatro grupos foram sacrificados após 7 dias e os outros grupos após 30 dias. As análises de imunohistoquímica e histopatologia foram realizada para examinar TLR2, TNFa OPG, colágeno-1 e as expressões de osteoblastos e osteoclastos. Houve maior expressão de TLR2, FGF2, OPG e colágeno-1, bem como maior número de osteoblastos. Enquanto isso, a expressão de TNFa e osteoclastos estava diminuída. O principal achado do estudo foi que a via de sinalização de TLR2 influenciou o processo de osteogênese do osso alveolar, reduzindo a atividade dos osteoclastos e estimulando o crescimento de osteoblastos induzido pela combinação de Aloe vera e EOEB.


Subject(s)
Animals , Male , Cattle , Aloe , Alveolar Process/growth & development , Cancellous Bone/transplantation , Osteogenesis , Signal Transduction , Toll-Like Receptor 2/metabolism , Collagen Type I/metabolism , Guinea Pigs , Heterografts , Osteoprotegerin/metabolism , Tooth Socket , Tumor Necrosis Factor-alpha/metabolism
12.
Braz. j. infect. dis ; 21(1): 42-50, Jan.-Feb. 2017. tab, graf
Article in English | LILACS | ID: biblio-839183

ABSTRACT

Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.


Subject(s)
Humans , Adult , HIV Infections/drug therapy , HIV-1/drug effects , Antiretroviral Therapy, Highly Active , Macrophages/drug effects , CD4-Positive T-Lymphocytes/drug effects , Case-Control Studies , HIV Infections/blood , Acute Disease , Chronic Disease , Interleukins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Treatment Outcome , CD4-CD8 Ratio , Statistics, Nonparametric , CD8-Positive T-Lymphocytes/drug effects , Chemokine CCL5/metabolism , Lipopolysaccharide Receptors/drug effects , Viral Load/drug effects , Chemokine CXCL10/metabolism
13.
Acta cir. bras ; 32(1): 28-37, Jan. 2017. graf
Article in English | LILACS | ID: biblio-837666

ABSTRACT

Abstract Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1β, TNF-α in spinal cord were determined. Results: Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1β, TNF-α were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.


Subject(s)
Animals , Male , Rats , Neuregulin-1/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetic Neuropathies/drug therapy , Neuralgia/drug therapy , Spinal Cord/metabolism , Random Allocation , Tumor Necrosis Factor-alpha/metabolism , Rats, Sprague-Dawley , Streptozocin , Nerve Growth Factor/metabolism , Interleukin-1beta/metabolism , Neuralgia/etiology
14.
Electron. j. biotechnol ; 25: 64-69, ene. 2017. tab, graf, ilus
Article in English | LILACS | ID: biblio-1008601

ABSTRACT

Background: MicroRNAs (miRNAs) are endogenous noncoding RNAs that regulate various biological processes. miR-125b is a miRNA that has been reported to be critical for hair follicle (HF) morphogenesis and development. We identified that the expression of miR-125b varies during an individual hair cycle (anagen, catagen, and telogen) in the skin of cashmere goats. We constructed a gain model (by overexpressing miR-125b) and a loss model (by inhibiting endogenous miR-125b) based on dermal papilla cells (DPCs) to further investigate the role of miR-125b in HF cycle. In addition, we used a dual-luciferase system to highlight the predicated target genes of miR-125b. Results: We found that miR-125b affects the expression of FGF5, IGF-1, SHH, TNF-α, MSX2, LEF-1, FGF7, NOGGIN, BMP2, BMP4, TGF-ß1, and ß-catenin. The dual-luciferase assay further validated a direct interaction between miR-125b and FGF5 and TNF-α. Conclusion: miR-125b affects the expression levels of genes related to hair cycle and may also play a critical role in regulating the periodic development of HF.


Subject(s)
Animals , Hair Follicle/growth & development , MicroRNAs/metabolism , Recombination, Genetic , Goats , Adenoviridae , Tumor Necrosis Factor-alpha/metabolism , Hair Follicle/cytology , Hair Follicle/metabolism , MicroRNAs/genetics , Fibroblast Growth Factor 5/metabolism , Enzyme Assays , Luciferases
15.
Yonsei Medical Journal ; : 206-216, 2017.
Article in English | WPRIM | ID: wpr-126255

ABSTRACT

PURPOSE: Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization and endothelial survival via inhibition of endothelial permeability and leukocyte- endothelium interactions. Hence, we hypothesized that treatment with umbilical cord mesenchymal stem cells (UCMSCs) carrying the Ang1 gene (UCMSCs-Ang1) might be a potential approach for acute lung injury (ALI) induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: UCMSCs with or without transfection with the human Ang1 gene were delivered intravenously into rats one hour after intra-abdominal instillation of LPS to induce ALI. After the rats were sacrificed at 6 hours, 24 hours, 48 hours, 8 days, and 15 days post-injection of LPS, the serum, the lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested for analysis, respectively. RESULTS: Administration of fluorescence microscope confirmed the increased presence of UCMSCs in the injured lungs. The evaluation of UCMSCs and UCMSCs-Ang1 actions revealed that Ang1 overexpression further decreased the levels of the pro-inflammatory cytokines TNF-α, TGF-β1, and IL-6 and increased the expression of the anti-inflammatory cytokine IL-10 in the injured lungs. This synergy caused a substantial decrease in lung airspace inflammation and vascular leakage, characterized by significant reductions in wet/dry ratio, differential neutrophil counts, myeloperoxidase activity, and BALF. The rats treated by UCMSCs-Ang1 showed improved survival and lower ALI scores. CONCLUSION: UCMSCs-Ang1 could improve both systemic inflammation and alveolar permeability in ALI. UC-derived MSCs-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of ALI.


Subject(s)
Acute Lung Injury/chemically induced , Angiopoietin-1/genetics , Animals , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Endotoxins , Genetic Therapy , Interleukin-10/metabolism , Interleukin-6/metabolism , Leukocyte Count , Lipopolysaccharides , Lung/metabolism , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Neutrophils/metabolism , Rats , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Umbilical Cord/cytology
16.
Braz. oral res. (Online) ; 31: e63, 2017. graf
Article in English | LILACS | ID: biblio-952122

ABSTRACT

Abstract This study was conducted to investigate the roles of different Toll-like receptor (TLR) signaling in Porphyromonas gingivalis (P. gingivalis)-induced and ligature-induced experimental periodontal bone resorption in mice. Wild-type (WT), TLR2 knockout (KO), TLR4KO, and TLR2&4 KO mice with C57/BL6 background were divided into three groups: control, P. gingivalis infection, and ligation. Live P. gingivalis or silk ligatures were placed in the sulcus around maxillary second molars over a 2-week period. Images were captured by digital stereomicroscopy, and the bone resorption area was measured with ImageJ software. The protein expression level of gingival RANKL was measured by ELISA. The gingival mRNA levels of RANKL, IL-1β, TNF-α, and IL-10 were detected by RT-qPCR. The results showed that P. gingivalis induced significant periodontal bone resorption in WT mice and TLR2 KO mice but not in TLR4 KO mice or TLR2&4 KO mice. For all four types of mice, ligation induced significant bone loss compared with that in control groups, and this bone loss was significantly higher than that in the P. gingivalis infection group. RANKL protein expression was significantly increased in the ligation group compared with that in the control group for all four types of mice, and in the P. gingivalis infection group of WT, TLR2 KO, and TLR4 KO mice. Expression patterns of RANKL, IL-1β, TNF-α, and IL-10 mRNA were different in the P. gingivalis infection group and the ligation group in different types of mice. In summary, P. gingivalis-induced periodontal bone resorption is TLR4-dependent, whereas ligation-induced periodontal bone resorption is neither TLR2- nor TLR4-dependent.


Subject(s)
Animals , Periodontitis/microbiology , Alveolar Bone Loss/etiology , Porphyromonas gingivalis/pathogenicity , Disease Models, Animal , Toll-Like Receptor 2/physiology , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/physiology , Time Factors , Enzyme-Linked Immunosorbent Assay , Reproducibility of Results , Alveolar Bone Loss/microbiology , Tumor Necrosis Factor-alpha/metabolism , Interleukin-10/metabolism , Mice, Knockout , Toll-Like Receptor 2/analysis , Toll-Like Receptor 4/analysis , Toll-Like Receptor 4/genetics , Interleukin-1beta/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Real-Time Polymerase Chain Reaction , Ligation , Metabolism , Mice, Inbred C57BL
17.
Braz. j. med. biol. res ; 50(8): e5163, 2017. graf
Article in English | LILACS | ID: biblio-888986

ABSTRACT

Pseudobrickellia brasiliensis (Asteraceae) is a plant commonly known as arnica-do-campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic extract of the plant has been used as an anti-inflammatory agent in folk medicine, but the biological mechanism of action has not been elucidated. The present study evaluated the composition of P. brasiliensis aqueous extract and its effects on pro-inflammatory cytokine production and lymphocyte proliferation. The extracts were prepared by sequential maceration of P. brasiliensis leaves in ethanol, ethyl acetate, and water. Extract cytotoxicity was evaluated by trypan blue exclusion assay, and apoptosis and necrosis were measured by staining with annexin V-FITC and propidium iodide. The ethanolic (ETA) and acetate (ACE) extracts showed cytotoxic effects. The aqueous extract (AQU) was not cytotoxic. Peripheral blood mononuclear cells stimulated with phorbol myristate acetate and ionomycin and treated with AQU (100 μg/mL) showed reduced interferon (IFN)-γ and tumor necrosis factor (TNF)-α expression. AQU also inhibited lymphocyte proliferative response after nonspecific stimulation with phytohemagglutinin. The aqueous extract was analyzed by liquid chromatography coupled with photodiode array detection and mass spectrometry. Quinic acid and its derivatives 5-caffeoylquinic acid and 3,5-dicaffeoylquinic acid, as well as the flavonoids luteolin and luteolin dihexoside, were detected. All these compounds are known to exhibit anti-inflammatory activity. Taken together, these findings demonstrate that P. brasiliensis aqueous extract can inhibit the pro-inflammatory cytokine production and proliferative response of lymphocytes. These effects may be related to the presence of chemical substances with anti-inflammatory actions previously reported in scientific literature.


Subject(s)
Humans , Anti-Inflammatory Agents/pharmacology , Asteraceae/chemistry , Cell Proliferation/drug effects , Interferon-gamma/drug effects , Lymphocytes/drug effects , Plant Extracts/pharmacology , Tumor Necrosis Factor-alpha/drug effects , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Interferon-gamma/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Plant Extracts/chemistry , Time Factors , Tumor Necrosis Factor-alpha/metabolism
18.
Braz. j. med. biol. res ; 50(6): e5868, 2017. tab, graf
Article in English | LILACS | ID: biblio-839308

ABSTRACT

We aimed to investigate the effect of etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, on rat cardiomyocyte hypertrophy and its underlying mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and then treated with different concentrations of etanercept (1, 10, and 50 μM). After treatment, cell counts, viability and cell apoptosis were evaluated. The mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT-PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were measured by western blotting. The protein levels of transforming growth factor-β1 (TGF-β1), interleukin (IL)-1β, IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1) were determined using enzyme linked immunosorbent assay (ELISA) kits. In the present study, TNF-α level in cardiomyocytes with hypertrophy was significantly enhanced (P<0.05). Compared to the model group, cell number and viability were significantly increased and ratio of apoptotic cells was reduced by etanercept (P<0.05, P<0.01, or P<0.001). In addition, etanercept remarkably reduced the mRNA levels of ANF, MMP-9 and MMP-13, inhibited the expression of Bax, and increased the expression of Bcl-2 compared to the model group (P<0.05). ELISA results further showed that etanercept lowered the levels of IL-1β, IL-6, LIF and CT-1 but not TGF-β1 compared to the model group (P<0.05). Etanercept may protect rat cardiomyocytes from hypertrophy by inhibiting inflammatory cytokines secretion and cell apoptosis.


Subject(s)
Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cardiomegaly/metabolism , Etanercept/pharmacology , Myocytes, Cardiac/drug effects , Protective Agents/pharmacology , Animals, Newborn , Apoptosis/drug effects , Atrial Natriuretic Factor/metabolism , Cardiomegaly/chemically induced , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Cytokines/drug effects , Disease Models, Animal , Inflammation/metabolism , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 9/metabolism , Myocytes, Cardiac/metabolism , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism
19.
Biol. Res ; 50: 42, 2017. tab, graf
Article in English | LILACS | ID: biblio-950888

ABSTRACT

BACKGROUND: Fresh frozen plasma (FFP) administration may increase the risk of nosocomial infections in parallel with the development of immune modulation. This could be driven by soluble mediators, possibly influencing the in vitro activation of human U937 monocyte cells, in a manner dependent on the age of the donors. METHODS: FFP donors were stratified into groups of 19-30 years, 31-40 years or 41-50 years, and U937 cells were cultured with FFP (alone or plus lipopolysaccharide-LPS) for 24 h. Both in FFP and supernatants, TNF, IL-1ß, IL-6, and IL-10 levels were measured by ELISA. Additionally, CD11B, TLR2, and CASP3 gene expression were measured by qtPCR in U937 cells. Total phagocytic activity was also assayed. RESULTS: Elevated IL-10, but low TNF and IL-1ß levels were measured in FFP from individuals aged 19-40 years, whereas in individuals aged 41-50 years FFP were characterized by equalized TNF and IL-10 levels. Elevated IL-6 levels were found in all FFP samples, especially in those from the oldest individuals. FFP stimulation was associated with striking modifications in cytokine production in an age-dependent way. Exposure to FFP attenuates the response to LPS. TLR2 and CD11B expression were enhanced regardless of the age of plasma donors, although CASP3 expression was increased only when FFP from individuals aged 19-40 years were tested. Phagocytosis decreased after exposure to FFP regardless of donor age. CONCLUSION: Our results suggest that soluble mediators in FFP may modulate the functioning of monocytes. Interestingly, this effect appears to be partially influenced by the age of donors.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Plasma/immunology , Blood Donors , Monocytes/immunology , Cytokines/immunology , U937 Cells/immunology , Enzyme-Linked Immunosorbent Assay , Monocytes/physiology , Age Factors , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-10/metabolism , Interleukin-1beta/metabolism
20.
Arq. bras. oftalmol ; 79(6): 357-362, Nov.-Dec. 2016. graf
Article in English | LILACS | ID: biblio-838758

ABSTRACT

ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.


RESUMO Objetivo: Avaliamos o efeito do licopeno, um carotenóide dietético e um potente anti-oxidante, sobre a inflamação ocular e estresse oxidativo em modelo de uveíte experimental. Métodos: Uveíte foi induzida por endotoxina (EIU) em ratos Sprague-Dawley por uma única injeção subcutânea de 200 ug de lipopolissacárido (LPS). A indução de EIU foi precedida por injeção intraperitoneal de licopeno em uma dose de 10 mg/kg (grupo LPS + Licopeno) ou veículo de mesmo volume (grupo LPS + Veículo), durante 3 dias consecutivos. O grupo controle positivo recebeu uma dose de 1 mg/kg de Dexametasona (grupo DEX + LPS) e o grupo controle negativo recebeu doses diárias de veículo mas sem LPS (grupo Controle Veículo). Vinte e quatro horas após a administração do LPS, os olhos foram enucleados, humor aquoso foi recolhido, e o número de células infiltrativas, a concentração de proteína, assim como os níveis de óxido nítrico (NO), fator de necrose tumoral α (TNF-α), interleucina-6 e marcadores de estresse oxidativo foram determinados no humor aquoso. Além disso, a resposta inflamatória foi avaliada clinicamente e histologicamente. Resultados: As células infiltrativas, concentração de proteína, o NO, TNF-α, interleucina-6 foram significativamente elevados no humor aquoso de ratos do grupo Grupo LPS + Veículo quando comparados ao Grupo Controle Veículo. O tratamento com licopeno diminuiu significativamente estes aumentos. Comparado ao Grupo LPS + Veículo, o licopeno reduziu significativamente as concentrações no humor aquoso dos marcadores de estresse oxidativo e NO (de 0,29 ± 0,1 μM para 0,19 ± 0,1 μM, p=0,003), o TNF-α (de 71,0 ± 22,3 ng/ml para 50,1 ± 2,1 ng/ml, p=0,043), interleucina-6 (de 121,6 ± 3,0 pg/ml para 111,1 ± 5,6 pg/ml, p=0,008). Do mesmo modo, o aumento do número de células infiltrativas no tecido uveal em seções histológicas foi significativamente inibido pelo licopeno, a pontuação inflamatória diminuiu de 2,0 ± 0,0 para 0,4 ± 0,5, p=0,001. Embora, não tenha sido estatisticamente significativo, o licopeno reduziu a contagem de células infiltrativas e a concentração de proteínas no humor aquoso. Conclusões: Estes resultados sugerem que o licopeno pode ter efeitos benéficos no tratamento da inflamação ocular, através dos seus efeitos anti-inflamatórios e antioxidantes.


Subject(s)
Animals , Rats , Uveitis/drug therapy , Carotenoids/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Aqueous Humor/metabolism , Uveitis/chemically induced , Uveitis/pathology , Lipopolysaccharides , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Rats, Sprague-Dawley , Oxidative Stress , Disease Models, Animal , Eye/pathology , Lycopene , Nitric Oxide/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL