Effect of FATP5 gene silencing on fatty hepatic cell inflammation / 中国药理学通报

Aim To determine the effect of FATP5 gene silencing on fatty hepatic cell inflammation and to explore its possible mechanism. Methods Five shR-NA sequences were designed and synthesized. The efficient FATP5-shRNA was screened by the siCHECK™ system. After preparing the FATP5-shRNA lentivirus, the FATP5 gene silence hepatic cell lines was obtained by HepG2 cell infection and puromycin screening. The FATP5 silencing efficiency was detected by Western blot. Then the oleic acid induced ROS and MDA generation, TNF-a and IL-6 protein expression and secretion, and NF-kB activation in FATP5 gene silence cells were analyzed by the detection kit, Western blot, nucleo-plasmic separation and reporter gene system. Results In the gene silence cells, FATP5 protein expression was reduced by 90% and the lipid accumulation was also significantly inhibited. Moreover, the FATP5 knockdown could reduce the oleic acid induced ROS and MDA generation, and suppress the NF-kB activation, thereby inhibiting the protein expression and secretion of TNF-a and IL-6. Conclusions FATP5 gene silence inhibits fatty hepatic cell inflammation, and its mechanism may be related to the inhibition of oxidative stress and lipid peroxidation.

The dual effect of acetate on microglial TNF-α production

Abstract Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases. HIGHLIGHTS Acetate was able to exacerbate the production of TNF-α in microglia. Acetate administered as pre-treatment to LPS acts as an anti-inflammatory. Histone deacetylase decreased TNF-α production in Acetate- and LPS-treated cells. Depending on the time of administration, Acetate modulates microglia's activation. Acetate may threaten neurodegenerative and neuropsychiatric diseases.

Terapias biológicas y tuberculosis en pediatría / Biological therapies and tuberculosis in pediatrics

En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.

In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children ́s age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.

Chloroquine ameliorates adriamycin-induced testicular damage by suppressing the inflammation and apoptosis in rats: a histological, immunohistochemical and biochemical study / La cloroquina mejora el daño testicular inducido por la adriamicina al suprimir la inflamación y la apoptosis en ratas: un estudio histológico, inmunohistoquímico y bioquímico

SUMMARY: Adriamycin (ADR) is an anthracycline antibiotic used for treatment of many types of cancer. However, its applications may damage to healthy tissues. Chloroquine (CLQ) is an anti-inflammatory agent used in treatment of many inflammation associated diseases such as malaria and rheumatoid arthritis. Moreover, it is used in the treatment of pneumonia caused by COVID-19. The aim of this study is to determine possible therapeutic effects of Chloroquine on Adriamycin-induced testicular toxicity in rats. We investigated the effect of CLQ on testicular injury caused by ADR. Rats were divided into four groups: Control, ADR, CLQ, ADR+CLQ. After administrations, animals were sacrificed, and testis tissues were extracted from the animals for the further examinations. Histopathological changes in testis tissues were evaluated and TNF-α and IL-6 immunostaining were performed to determine the expression levels of these cytokines. TUNEL method were used for evaluation of apoptotic index. Moreover, serum testosterone levels were measured by ELISA assay. We observed that ADR group showed histopathological deterioration when compared to the Control group and CLQ treatment ameliorated this damage induced by Adriamycin.An increase in TNF-α and IL-6 immunoreactivities and in the number of apoptotic cells and a decrease in serum testosterone levels were determined in the ADR group compared to the Control and CLQ group. Furthermore, our examinations showed an improvement in testicular tissue in ADR+CLQ group in terms of these parameters when compared to the ADR group. We suggest that CLQ can be used as a protective agent to reduce the toxic effects of Adriamycin as a result of its anti-inflammatory and anti-apoptotic properties.

RESUMEN: La adriamicina (ADR) es un antibiótico de antraciclina que se usa para el tratamiento de muchos tipos de cáncer. Sin embargo, sus aplicaciones pueden dañar los tejidos sanos. La cloroquina (CLQ) es un agente antiinflamatorio que se utiliza en el tratamiento de enfermedades asociadas a la inflamación, tal como la malaria y la artritis reumatoide. También se utiliza en el tratamiento de la neumonía causada por COVID-19. El objetivo de este estudio fue determinar los posibles efectos terapéuticos de la cloroquina sobre la toxicidad testicular inducida por adriamicina en ratas. Investigamos el efecto de CLQ sobre la lesión testicular causada por ADR. Las ratas se dividieron en cuatro grupos: Control, ADR, CLQ, ADR + CLQ. Después de las administraciones, se sacrificaron los animales y se extrajeron los testículos de los animales para los exámenes adicionales. Se evaluaron los cambios histopatológicos en los tejidos testiculares y se realizó la inmunotinción de TNF-α e IL-6 para determinar los niveles de expresión de estas citocinas. Se utilizó el método TUNEL para la evaluación del índice apoptótico. Además, los niveles de testosterona en suero se midieron mediante un ensayo ELISA. El grupo ADR mostró un deterioro histopatológico en comparación con el grupo Control y observamos que el tratamiento con CLQ mejoró el daño inducido por Adriamicina. Un aumento en las inmunorreactividades de TNF-α e IL-6 y en el número de células apoptóticas además de una disminución en los niveles séricos de testosterona se determinaron en el grupo de ADR en comparación con el grupo de control y CLQ. Además, nuestros exámenes mostraron una mejora en el tejido testicular en el grupo ADR + CLQ en términos de estos parámetros en comparación con el grupo ADR. Sugerimos que CLQ se puede utilizar como agente protector para reducir los efectos tóxicos de la Adriamicina, gracias a sus propiedades antiinflamatorias y antiapoptóticas.

Determination of tnf-a gene polymorphisms on skeletal pattern in class ii malocclusion

Abstract Bone development and growth is a non-going, life-long process, varying greatly among individuals and much of this variation could be modulated by genetic factors. The purpose of this study was to evaluate the association between the polymorphisms in the TNF-a gene and skeletal class II malocclusion. Single nucleotide polymorphisms in TNF-a (rs1799724; rs1800629) gene were studied in 79 skeletal class II malocclusion and 102 skeletal class I malocclusion subjects from Straight Wire Group of Studies on Orthodontics and Functional Orthopedics for Maxillary from Rio de Janeiro, Brazil. The Genotyping of these selected polymorphisms was carried out by TaqMan real-time PCR using genomic DNA extracted from buccal cells. All allele and genotype frequencies were compared between the groups using the PLINK® software in a free, in a dominant and in a recessive model using a chi-square test (p≤0.05). There was no significant association of TNF-a (rs1799724; rs1800629) genotype and allele distribution with skeletal class II malocclusion. Regardless of the dominant or recessive genetic model, the preferential genotype associations for rs1799724 and rs1800629 was insignificant. In conclusion, no evidence of association is apparent between genetic polymorphisms involving TNF-a and skeletal class II malocclusion or the position of the maxilla and mandible in the postero-anterior direction.

Resumo O desenvolvimento e crescimento ósseo é um processo contínuo, que dura toda a vida, variando muito entre os indivíduos e grande parte dessa variação pode ser modulada por fatores genéticos. O objetivo deste estudo foi avaliar a associação entre os polimorfismos no gene TNF-a e a má oclusão da classe II esquelética. Polimorfismos no gene TNF-a (rs1799724; rs1800629) foram estudados em 79 indivíduos com má oclusão esquelética de classe II e 102 indivíduos com má oclusão esquelética classe I do Grupo de Estudos em Ortodontia e Ortopedia Funcional dos Maxilares do Rio de Janeiro, Brasil. A genotipagem destes polimorfismos foi realizada por PCR em tempo real, através de DNA genômico extraído de células bucais. Todas as frequências alélicas e genotípicas foram comparadas entre os grupos utilizando o software PLINK® em um modelo livre, dominante e recessivo. Foi aplicado o teste do qui-quadrado (p≤0,05). Não houve associação significativa na distribuição genotipica e alélica do gene TNF-a (rs1799724; rs1800629) com a má oclusão de classe II esquelética. Independentemente do modelo genético dominante ou recessivo, as associações genotípicas preferenciais para rs1799724 e rs1800629 foram insignificantes. Pode-se concluir que, não existe evidência de associação entre polimorfismos genéticos envolvendo TNF-a e má oclusão esquelética de classe II ou a posição da maxila e mandíbula na direção póstero-anterior.

Protective effect of Rhododendron weyrichii flower extract against UVB-induced proinflammatory cytokine production in human keratinocytes

Ultraviolet B (UVB) radiation is harmful to the skin and induces cytokine release from keratinocytes leading toinflammatory skin disorders. Previous studies have shown that chronic exposure to UVB radiation increases tumornecrosis factor (TNF)-α and interleukin (IL)-6 secretion through various signaling pathways, resulting in skininflammation and increased risk of skin cancer. The present study was undertaken to investigate the protective effectsof Rhododendron weyrichii flower (RWF) extracts against UVB damage of immortalized human keratinocytes(HaCaT). To determine the anti-inflammatory effects of RWF, we examined UVB-induced proinflammatory cytokineproduction in HaCaT cells in the presence or absence of RWF extract, using enzyme-linked immunosorbent assay(ELISA). The results indicated that the RWF extract inhibited the production of proinflammatory molecules suchas IL-6 and TNF-α, but not IL-8, in UVB-irradiated HaCaT cells. These results demonstrate that RWF potentiallyprotects against UVB-induced skin inflammation. In addition, using high-performance liquid chromatography (HPLC)fingerprinting, kaempferol (0.335 ppm) and astragalin (2.569 ppm) were identified and quantified as RWF extractconstituents. Moreover, we tested the potential application of RWF extracts as a cosmetic treatment by performinghuman skin primary irritation tests. In these tests, the RWF extracts did not induce adverse reactions. Based on theseresults, we suggest that RWF extracts be considered anti-inflammatory candidates for pharmaceutical and/or cosmeticapplications.

Resveratrol protects against atherosclerosis action by regulating long noncoding RNA malat1 / 中国药理学通报

Aim To investigate the protective effect of resveratrol( Rev) on atherosclerosis( AS) , and clarify the rolcof Rev in regulating IncRNA MALATi (MALAT1) and the role of MALATI in AS. Methods ApoE'/ mice were randomly divided into two groups-, the high-fat diet(HFD) group, the HFD plus Rev treatment group, and the atherosclerosis model was established for 16 weeks. Hematoxylin-eosin( HE) staining was used to detect the area of aortic plaques in mice. And electron microscopy was performed to measure the formation of foam cells. The effects of Rev on MALATI, inflammatory cytokine ( 1L-6, 1L-1(3 and TNF-a) were examined using real time PCR. In addition, the roles of MALATI on inflammatory cytokine, and the influence of free cholesterol (FC) on the ex pression of MALATI were measured by real time PCR. Results The Rev treatment group significantly reduced arterial plaque areas and foam cell formation. In normal peritoneal macrophages, Rev could increase the expression of MALATI, and FC could down-regulate MALATI. Furthermore, Rev could decrease the expression of IL-6, 11,-1(3 and TNF-a in a dose-dependent manner. Knockdown of MALATI promoted the mRNA expression of IL-6 and TNF-a. Conclusions Rev may modulate the expression of inflammatory cytokine IL-6, lL-lp and TNF-a by affecting the level of MALAT, thereby exerting the anti-atherogenic effects.

Changes in peripheral blood inflammatory factors (TNF-a and IL-6) and intestinal flora in AIDS and HIV-positive individuals / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4+ T lymphocytes. Methods: Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4+ T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4+ T lymphocyte values were evaluated using the Spearman correlation coefficient. Results: The levels of TNF-a and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4+ T lymphocytes was lower. The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faecium were much higher. The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-a and IL-6 and the CD4+ T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium. Conclusions: The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4+ T lymphocytes and the levels of TNF-a and IL-6.

Estado proinflamatorio en niños obesos / Proinflammatory state in obese children

INTRODUCCIÓN: La presencia de un estado de inflamación de bajo grado en niños obesos, se debería, entre otros factores, a que el tejido adiposo de los obesos produce moléculas proinflamatorias que contribuyen al desarrollo de aterosclerosis. OBJETIVO: Determinar en una población de niños obesos los niveles séricos de ligando CD-40 soluble (sCD40L), proteína quimioatractante de monocitos 1 (MCP-1), interleuquina 6 (IL-6), Factor de Necrosis tumoral a (TNF-a) y Proteína C Reactiva ultrasensible (PCR-us), comparados con un grupo control y analizar la correlación de estas moléculas con las variables antropométricas y metabólicas. PACIENTES Y MÉTODO: Estudio transversal de 37 niños obesos de 8 a 12 años y 20 niños con peso normal. A todos los pacientes se les realizó una historia clínica consignando edad, peso, talla, IMC, circunferencia de cintura, estadios de Tanner y antecedentes familiares. Se determinaron los niveles séricos de sCD40L, MCP-1, IL-6, TNF-a y PCR-us mediante ELISA, PCR-us por quimioluminiscencia, glucemia, insulina plasmática, perfil lipídico y se calculó el índice HOMA. Los datos se expresaron como la mediana y rango intercuartil y se utilizó el coeficiente de Spearman para investigar las correlaciones entre variables. RESULTADOS: Los niños obesos presentaron valores significativamente mayores de sCD40L, MCP-1, IL-6, TNF-a, PCR-us que los niños controles. El índice de masa corporal y la circunferencia de cintura se correlacionaron positivamente con sCD40L y MCP-1. CONCLUSIÓN: Los niveles elevados de las moléculas estudiadas sugieren la presencia de inflamación de bajo grado asociada a obesidad en esta población.

INTRODUCTION: Obesity is a chronic disease that affects adults as well as children and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. One of the reasons for the presence of low-grade inflammation in these patients could be that adipose tissue of the obese produces proin flammatory molecules that favor the development of atherosclerosis. OBJECTIVE: To determine serum levels of soluble CD40 ligand (sCD40L), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-Α) and high sensitivity CRP (hsCRP), in an obese chil dren population compared to a control group, also to analyze the correlation of these molecules with the anthropometric and metabolic variables. PATIENTS AND METHOD: A cross-sectional, observational study was carried out on 37 obese children, aged 8 to 12 years, and 20 children with normal weight. Serum levels of sCD40L, MCP-1, IL-6, TNF-Α and hsCRP were determined. Data were expressed as the median and interquartil range and Spearman coefficient was used to investigate correlations between variables. RESULTS: Compared to the control group, obese children presented significantly higher values of sCD40L, MCP-1, IL-6, TNF-Α, and hsCRP than control group. Body mass index and waist circumference correlated positively with sCD40L and MCP-1. CONCLUSION: Elevated levels of the studied molecules studied suggest the presence of low-grade inflammation associated with obesity in this population.

Protective effects of melatonin on spinal cord injury / Efectos protectores de la melatonina en lesión de la médula espinal

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.

The effects of antidepressants on inflammatory factors of frontal lobe in depression model rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of antidepressants on frontal lobe inflammatory factors in depressed model rats.Methods Thirty SD rats were randomly divided into 5 groups (n=6):contorl group(Cn),depression group (Dn),citalopram group (Dx),venlafaxine group (Dw) and reboxetine group (Dr).The open field test and sugar consumption test were performed to observe the depression behavior and the changes of FGF-1,TNF-α,IL-1 and CRP were measured in frontal lobe of rats by ELISA.Pearson linear correlation analysis was used to evaluate the correlation between behavioral score and inflammatory factors level in rats.Results (1)Compared with the Cn group,the scores of Dn,Dr,Dw,Dx group were decreased on Open field test and sugar consumption test (P＜0.05).Compared with the Dn group,the scores of the Dx,Dw,Dr group were increased in Open field test and sugar consumption test (P＜0.05).(2)Compared with Cn group,the levels of TNF-α,IL-1 and CRP increased in Dn group and FGF-1 level decreased (P＜0.01).Compared with Dn group,the levels of FGF-1 increased in Dx ((86.54±2.56) ng/L),Dw((79.82±4.89) ng/L)and Dr ((68.50 ± 3.61) ng/L) group,however,the levels of TNF-α decreased in Dx ((150.21±5.65) ng/L),Dw ((161.28±8.80) ng/L),Dr ((175.78±9.67) ng/L) group,and the level of IL-1 also decreased in Dx ((30.87±4.48) ng/L),Dw ((36.65±3.33) ng/L),Dr ((40.14±2.81)ng/L) group,and the levels of CRP also decreased in Dx ((374.88 ± 14.15) ng/L),Dw ((394.21 ± 17.03) ng/L),Dr ((414.34± 10.97)ng/L) (P＜0.01).(3)The behavioral score of each group was positively correlated with of FGF-1 and negatively correlated with TNF-a,IL-1 and CRP (P＜0.05).Conclusion Antidepressants can reduce the level of proinflammatory factors and increase the level of anti-inflammatory factors of frontal lobe in depression model rats,suggesting that antidepressants may play an antidepressant effect by regulating the concentration of inflammatory factors.

Association of TNFA (−308G/A), IFNG (+874 A/T) and IL-10 (−819 C/T) polymorphisms with protection and susceptibility to dengue in Brazilian population

Objective To evaluate gene polymorphisms and their association with susceptibility to dengue. Methods A retrospective case-control study was performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system. Results We observed a protective association of IL-10 (−819 C/T) C allele (P = 0.028, OR = 0.56, CI = 0.34–0.91) against DHF, while the C/T (P = 0.047, OR = 2.10, CI = 1.01–4.38) and T/T (P = 0.008, OR = 3.82, CI = 1.38–10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA −308 GA + AA (P = 0.043, OR = 0.45, CI = 0.20–1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG (+874 A/T) A/T genotype against DF (P = 0.02, OR = 0.46, CI = 0.24–0.89) and DHF (P = 0.034, OR = 0.43, CI = 0.19–0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA (P = 0.022, OR = 2.95, CI = 1.18–7.41) was statistically significantly associated with susceptibility to DF and the combination GCT (P = 0.035, OR = 0.28, CI = 0.08–0.90) with protection against the development of DHF. Conclusions This research identifies the association of the IFNG (+874 A/T), TNFA (−308G/A), IL-10 (−819 C/T) genotypes as a factor for protection, susceptibility and severity to dengue.

Association of TNFA (-308G/A), IFNG (+874 A/T) and IL-10 (-819 C/T) polymorphisms with protection and susceptibility to dengue in Brazilian population

OBJECTIVE@#To evaluate gene polymorphisms and their association with susceptibility to dengue.@*METHODS@#A retrospective case-control study was performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system.@*RESULTS@#We observed a protective association of IL-10 (-819 C/T) C allele (P = 0.028, OR = 0.56, CI = 0.34-0.91) against DHF, while the C/T (P = 0.047, OR = 2.10, CI = 1.01-4.38) and T/T (P = 0.008, OR = 3.82, CI = 1.38-10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA -308 GA + AA (P = 0.043, OR = 0.45, CI = 0.20-1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG (+874 A/T) A/T genotype against DF (P = 0.02, OR = 0.46, CI = 0.24-0.89) and DHF (P = 0.034, OR = 0.43, CI = 0.19-0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA (P = 0.022, OR = 2.95, CI = 1.18-7.41) was statistically significantly associated with susceptibility to DF and the combination GCT (P = 0.035, OR = 0.28, CI = 0.08-0.90) with protection against the development of DHF.@*CONCLUSIONS@#This research identifies the association of the IFNG (+874 A/T), TNFA (-308G/A), IL-10 (-819 C/T) genotypes as a factor for protection, susceptibility and severity to dengue.

Changes in histopathology and tumor necrosis factor-α levels in the hearts of rats following asphyxial cardiac arrest

OBJECTIVE: Post cardiac arrest (CA) syndrome is associated with a low survival rate in patients who initially have return of spontaneous circulation (ROSC) after CA. The aim of this study was to examine the histopathology and inflammatory response in the heart during the post CA syndrome. METHODS: We induced asphyxial CA in male Sprague-Dawley rats and determined the survival rate of these rats during the post resuscitation phase. RESULTS: Survival of the rats decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2 days after ROSC, and their heart tissues were examined. Histopathological scores increased at 12 hours post CA and afterwards, histopathological changes were not significant. In addition, levels of tumor necrosis factor-α immunoreactivity gradually increased after CA. CONCLUSION: The survival rate of rats 2 days post CA was very low, even though histopathological and inflammatory changes in the heart were not pronounced in the early stage following CA.

Association between TNF -308G/A polymorphism and susceptibility to pulmonary tuberculosis in the Lur population of Iran

Objective: To investigate whether tumor necrosis factor-a (TNFa) -238G/A and -308G/A polymorphisms are associated with susceptibility to pulmonary tuberculosis (TB) in the Lur ethnic population of Iran. Methods: TNF polymorphisms genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method in 100 pulmonary TB patients and 100 healthy controls from the Lur population. Results: The allelic and genotypic frequencies of TNFa -238G/A polymorphism were not significantly different between the pulmonary TB patients and the healthy controls. However, the TNFa -308G/A polymorphism showed a significantly higher frequency of genotype GG in TB subjects compared to healthy controls (94% in the patients vs. 62% in the controls, P = 0.0001, odds ratio = 0.104, confidence interval = 0.028–0.382). Moreover, in the TNFa -308G/A polymorphism, a significantly higher frequency of G allele was measured in the patient group compared with the control group (97% in the patient group vs. 81% in the control group, P = 0.0001, odds ratio = 0.132, confidence interval = 0.038–0.462). Conclusions: Our findings suggest that TNFa -308G/A polymorphism may increase the susceptibility to pulmonary TB in the Lur population of Iran. Despite TNFa poly-morphisms and susceptibility to pulmonary TB, we suggest that more studies with larger sample size are needed in the future. Increasing our understanding of susceptibility risk factors may help to improve current preventive measures and treatment for TB.

Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline - A longitudinal analysis after using TNFa blockers

Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFatherapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity / Associação de neopterina como marcador de ativação do sistema imunológico e atividade da artrite reumatoide juvenil

OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p < 0.05). A statistically significant higher mean level serum neopterin concentration (p < 0.05) was found in JIA patients (20.43 ± 8.73 nmol/L) than in controls (6.88 ± 2.87 nmol/L) (p < 0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-a, IL-6, MCP-1, and JADAS-27 (p < 0.05). No correlation was found between serum neopterin and CRP (p > 0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05).CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

OBJETIVO: Avaliar as concentrações plasmáticas de neopterina em pacientes com artrite idiopática juvenil (AIJ) ativa e correlacioná-las com a atividade da doença.MÉTODOS: Foram recrutados da clínica de Alergia e Imunologia Infantil da Universidade Ain Shams 60 pacientes diagnosticados com AIJ ativa, bem como 60 crianças aparentemente saudáveis com a mesma idade e o mesmo sexo no grupo de controle. A atividade da doença foi avaliada pelo Escore de Atividade da Doença da Artrite Juvenil em 27 Articulações (JADAS-27). Foram feitas investigações laboratoriais em todos os pacientes, incluindo a determinação da concentração de hemoglobinas, a taxa de sedimentação de eritrócitos e a proteína C-reativa. Foram mensuradas as concentrações séricas do fator de necrose tumoral alfa, interleucina-6 e proteína quimiotática de monócitos-1 e neopterina.RESULTADOS: Foi encontrada uma diferença significativa entre os pacientes com AIJ e os controles quanto às médias de Hb, TSE, FNT-a, IL-6 e MCP-1 (p < 0,05). Foi encontrado um nível estatística e significativamente maior de concentração média de neopterina sérica (p < 0,05) em pacientes com AIJ (valor médio de 20,43 ± 8,73 nmol/L) do que em controles (valor médio de 6,88 ± 2,87 nmol/L) (p < 0,05). Foram detectadas correlações positivas significativas entre a neopterina sérica e TSE, FNT-a, IL-6, MCP-1 e JADAS-27 (p < 0,05). Não foi encontrada correlação entre a neopterina sérica e a PCR (p > 0,05). A análise de regressão linear múltipla mostrou que o JADAS-27 e a TSE foram as principais variáveis associadas à neopterina sérica em pacientes com AIJ (p < 0,05).CONCLUSÃO: A elevação das concentrações plasmáticas de neopterina em pacientes com AIJ precoce pode indicar um estímulo de resposta imune. A neopterina sérica pode ser usada como um indicador sensível para analisar o histórico de inflamações e o escore de atividade da doença em pacientes com AIJ.

Serum levels of soluble TNF-a receptors but not BDNF are associated with apathy symptoms in mild Alzheimer's disease and amnestic mild cognitive impairment / Níveis Séricos de receptores Solúveis Do TNF-a mas não de BDNF estão associados a sintomas de apatia na doença de Alzheimer leve e no comprometimento cognitivo leve amnéstico

Apathy is intimately associated with dementia. Unfortunately, its pathophysiology remains poorly understood. The motivational impairment that characterizes this disorder might share the same inflammatory mechanisms, as suggested by the sickness behavior theory. OBJECTIVE: The primary aim of this study was to investigate the association between apathy symptoms and serum levels of tumor necrosis factor alpha (TNF-a) and its soluble receptors. Brain-derived neurotrophic factor (BDNF) levels were also analyzed since these have been associated with depression, a condition which shares abulic features with apathy. METHODS: The sample consisted of 27 subjects with mild Alzheimer's disease or amnestic mild cognitive impairment, who were submitted to specific apathy evaluation using the Apathy Scale (AS) and provided blood samples for biomarker analysis. Participants were categorized into two groups according to median AS scores (17 points). RESULTS: Subjects with higher apathy symptoms (n=13) displayed higher levels of TNF-a soluble receptors (type 1: p=0.03; type 2: p=0.04). No other difference was found between groups. CONCLUSION: These findings point to the involvement of inflammatory mediators in the genesis of apathy symptoms, as suggested by the sickness behavior theory.

Apatia está intimamente associada à demência. Lamentavelmente, sua fisiopatologia ainda é pouco compreendida. O comprometimento motivacional que caracteriza este transtorno poderia compartilhar mecanismos inflamatórios como sugere a teoria do comportamento associado à doença. OBJETIVO: O principal objetivo deste estudo foi investigar a associação entre apatia e os níveis séricos do fator de necrose tumoral alfa (TNF-a) e de seus receptores solúveis. Os níveis de fator neurotrófico derivado do cérebro também foram analisados já que estes foram associados à depressão, que compartilha aspectos abúlicos com a apatia. MÉTODOS: A amostra consistiu de 27 indivíduos com doença de Alzheimer leve ou com comprometimento cognitivo leve amnéstico, que foram submetidos à avaliação de apatia pela Escala de Apatia (EA), e proveram amostra de sangue para análise de biomarcadores. De acordo com a mediana de escores na EA (17 pontos), a amostra foi divida em dois grupos. RESULTADOS: O grupo com mais sintomas de apatia apresentou maiores níveis séricos de receptores solúveis de TNF-a (tipo 1: p=0,03 ; tipo 2: p=0,04). Nenhuma outra diferença foi encontrada entre os grupos.CONCLUSÃO: Estes achados sugerem o envolvimento de mediadores inflamatórios na gênese de sintomas de apatia, assim como sugere a teoria do comportamento associado à doença.

Factor de necrosis tumoral alfa en una población infanto-juvenil con sobrepeso / Tumor necrosis factor-alpha in a children population with overweight

El sobrepeso infantil está asociado a sobrepeso/obesidad en la edad adulta. El tejido adiposo en obesos produce una cantidad incrementada de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF-a), ejerciendo un efecto deletéreo sobre la función vascular. El objetivo de este trabajo fue evaluar niveles de TNF-a en una población infantojuvenil con sobrepeso y su relación con otras variables. Se estudiaron 30 niños con sobrepeso (12 varones) de edades entre 8-13 años, se midió circunferencia de cintura (CC) e índice de masa corporal (IMC) y fueron comparados con 20 controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC = 85 < 95 percentilo para edad y sexo. En ambos grupos se determinó: glucemia en ayunas (método glucosa oxidasa), insulina plasmática (ECLIA), fibrinógeno (Fg, método de Clauss), proteína C reactiva ultrasensible (uPCR, método inmunoturbidimétrico), TNF-a (ELISA), perfil lipídico (métodos enzimáticos), eritrosedimentación y se calculó el índice HOMA. Los datos se expresaron como mediana y rango intercuartil y con el coeficiente de Spearman se investigaron las correlaciones entre variables, considerándose significativo un p < 0.05. Los niveles de TNF-a fueron mayores en los sujetos con sobrepeso [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. También resultaron más elevados los valores de Fg, insulina plasmática, índice HOMA, uPCR y triglicéridos. El TNF-a se correlacionó con la CC (r = 0.654; p = 0.021). Los niveles elevados de TNF-a, uPCR y Fg encontrados confirman un estado proinflamatorio asociado a obesidad abdominal en la población estudiada.

The child overweight is associated with overweight/obesity at the adult age. The obese adipose tissue produces an increase of proinflammatory cytokines as the tumor necrosis factor alpha (TNF-a), causing a deleterious effect on vascular functions. The aim of this work was to evaluate TNF-a levels in a children’s population with overweight and its relationship with clinical and laboratory variables. Thirty overweight children were studied, with ages between 8-13 years old, and twenty control children. In both groups waist circumference was measured and body mass index (BMI) calculated. The inclusion criterium was a >85th < 95 th BMI percentile for age and sex. In both groups were determined: fasting blood glucose (glucose-oxidase method); plasma insulin (ECLIA); plasma fibrinogen (Fg, Clauss method); high sensitivity C reactive protein (hsCRP, immunoturbidimetric method); plasma myeloperoxidase (ELISA); TNF-a (ELISA); lipid profile (enzymatic methods); erythrosedimentation rate (ESR) and homeostasis model assessment index (HOMA). Data were expressed as the median and interquartile range. Correlations between variables were investigated with the Spearman’s coefficient. A p < 0.05 was considered significant. The TNF-a levels were higher in overweight children [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. Levels of Fg, plasma insulin, HOMA index, uCRP and triglycerides were also statistically significant higher than the control group. The TNF-a was positively correlated with the waist circumference (r = 0.654; p = 0.021). The high TNF-a levels found, with the CRP and Fg levels, confirm a low grade proinflammatory state associated to abdominal obesity in the studied population.

Participación de los mediadores de la respuesta inmune inflamatoria en la resorción del hueso alveolar durante la periodontitis crónica: revisión de la literatura / Participation of the immune response mediators in inflamatory alveolar bone resortion during chronic periodontitis: a literature review

La enfermedad pulmonar obstructiva crónica (EPOC) abarca todas aquellas enfermedades respiratorias que cursan con obstrucción no totalmente reversible del flujo aéreo. La limitación es progresiva y está asociada a una respuesta inflamatoria. La denominación de fenotipo se utiliza para referirse a formas clínicas de los pacientes con EPOC, describiéndose: 1. No agudizador, con enfisema o bronquitis crónica, 2. Mixto EPOC-asma, 3. Agudizador con enfisema y 4. Agudizador con bronquitis crónica. La superposición de los síntomas hace difícil el diagnóstico, y para la mayoría de los pacientes, el tabaquismo es el factor etiológico más importante. La obstrucción de las vías bronquiales en el asma es esencialmente reversible, pero muchos años de exacerbaciones recurrentes puede producir una obstrucción permanente debido al remodelado de las vías respiratorias. La inflamación crónica esta asociada a un aumento en la hiperreactividad de la vía aérea que conduce a episodios recurrentes de sibilancias, disnea, opresión torácica y tos, particularmente en la noche o temprano en la mañana. Estos episodios se asocian generalmente a la obstrucción generalizada pero variable en el flujo aéreo pulmonar que es frecuentemente reversible espontáneamente o con tratamiento

Chronic obstructive pulmonary disease (COPD) includes all those respiratory diseases that curse with not fully reversible obstruction of the airflow. The limitation is progressive and its associated with a inflammatory response. The denomination of phenotype is used to refer to clinical forms of COPD patients, describing: 1. No peaking, emphysema or chronic bronchitis, 2. Mixed COPD-asthma, 3. Peaking with emphysema and 4. Peaking with chronic bronchitis. The superposition of the symptoms makes the diagnosis difficult, and for most patients, smoking is the most important etiologic factor. The bronchial airway obstruction in asthma is essentially reversible, but many years of recurrent exacerbations can produce a permanent obstruction due to airway remodelling. Chronic inflammation is associated with increased airway hyper responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early in the morning. These episodes are usually associated with widespread but variable obstruction in lung airflow that is often reversible either spontaneously or with treatment