SUMMARY: This study aimed to explore the potential of Nasturtium officinale L. leaves extract (NOLE) in safeguarding hepatocytes against N-diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) by investigating its effects on biochemical, molecular, and antioxidant pathways. The study also delved into NOLE's role in modulating the HOTAIR/miR-124/Notch1 axis pathway. In this study, 50 Wistar rats were divided into five groups (n=10/group): normal, HCC-induced (100 mg/kg DEN), HCC rats treated with 100 and 200 mg/kg DEN + NOLE, and normal rats treated with 200 mg/kg NOLE. At the study's conclusion, serum levels of liver function markers (such as albumin, total protein, bilirubin, C-reactive protein, ALT, AST, and ALP), inflammatory cytokines (IL-6, IL- 1b, IL-10, and TNF-a), and oxidative parameters [including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) enzyme activity, and nitric oxide (NO) levels] were assessed. The levels of HOTAIR, miR-124, Notch1, and Jagged1 genes and proteins in liver tissue were measured. Immunohistochemical analysis was used to evaluate P53-positive cells in liver hepatocytes. DEN administration led to significant alterations in body and liver weight, serum liver enzymes, antioxidant levels, inflammatory markers, and expression of genes/proteins related to the HOTAIR/miR-124/Notch1 axis in liver pathways. NOLE exhibited dose-dependent effects in mitigating these changes, notably enhancing weight, liver health, antioxidant capacity, and inflammatory responses, especially at the 200 mg/kg dosage. Histopathological assessments revealed structural improvements in liver tissue with NOLE treatment. In conclusion, our study highlights the potential of NOLE in exerting anti-cancer effects against DEN-induced HCC.

RESUMEN: Este estudio tuvo como objetivo explorar el potencial del extracto de hojas de Nasturtium officinale L. (NOLE) para proteger los hepatocitos contra el carcinoma hepatocelular (HCC) inducido por N-dietilnitrosamina (DEN) mediante la investigación de sus efectos sobre las vías bioquímicas, moleculares y antioxidantes. El estudio también profundizó en el papel de NOLE en la modulación de la vía del eje HOTAIR/miR-124/Notch1. En este estudio, 50 ratas Wistar se dividieron en cinco grupos (n=10/ grupo): ratas normales, inducidas por HCC (100 mg/kg de DEN), ratas con HCC tratadas con 100 y 200 mg/kg de DEN + NOLE y ratas normales tratadas con 200 mg/kg de NOLE. Al concluir el estudio, se midieron los niveles séricos de marcadores de función hepática (como albúmina, proteína total, bilirrubina, proteína C reactiva, ALT, AST y ALP), citoquinas inflamatorias (IL-6, IL-1β, IL-10 y TNF-α) y parámetros oxidativos [incluidos los niveles de glutatión peroxidasa (GPx), superóxido dismutasa (SOD), catalasa (CAT) y óxido nítrico (NO)]. Se midieron los niveles de los genes y proteínas HOTAIR, miR-124, Notch1 y Jagged1 en el tejido hepático. Se utilizó análisis inmunohistoquímico para evaluar las células P53 positivas en los hepatocitos del hígado. La administración de DEN provocó alteraciones significativas en el peso corporal y hepático, las enzimas hepáticas séricas, los niveles de antioxidantes, los marcadores inflamatorios y la expresión de genes/proteínas relacionadas con el eje HOTAIR/miR-124/Notch1 en las vías hepáticas. NOLE exhibió efectos dependientes de la dosis para mitigar estos cambios, en particular mejorando el peso, la salud del hígado, la capacidad antioxidante y las respuestas inflamatorias, especialmente en la dosis de 200 mg/kg. Las evaluaciones histopatológicas revelaron mejoras estructurales en el tejido hepático con el tratamiento NOLE. En conclusión, nuestro estudio destaca el potencial de NOLE para ejercer efectos anticancerígenos contra el CHC inducido por DEN.

SUMMARY: Cerebral hemorrhage (CH) presents a significant risk for cognitive decline. Our research aimed to assess the impact of Apricot Kernel Oil (AKO) on cognitive function and inflammatory response in a hemorrhagic stroke model using Wistar rats, and to examine their correlation. Fifty Wistar rats were randomly assigned to five groups: a control group, an AKO supplemented group (receiving 400 mg/kg AKO), a CH group (with induced CH), and CH groups supplemented with 200 and 400 mg/kg AKO, each containing 10 rats. Cognitive function was evaluated using the Y-electric maze test across these groups. Additionally, enzyme-linked immunosorbent assay and real-time PCR were utilized to analyze the protein and gene expression profiles of inflammatory and apoptotic factors in the brain. Compared to the control group, rats in the CH group took longer to master the maze criteria (P<0.05). Moreover, the CH group exhibited significantly increased levels of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and decreased levels of anti-inflammatory cytokines IL-4 and IL-10 compared to the control group (P<0.05). Conversely, rats in the CH+400 mg/kg AKO group showed opposite trends in electrical simulation time, inflammatory factor protein, and gene expression profile (Bcl- 2, BAX, Caspase-3, and p53) compared to the CH group (P<0.05). Our findings suggest that AKO extract may ameliorate cognitive dysfunction following CH in rats, potentially through modulation of inflammatory factors secreted by microglia.

RESUMEN: La hemorragia cerebral (HC) presenta un riesgo significativo de deterioro cognitivo. Nuestra investigación tuvo como objetivo evaluar el impacto del aceite de semilla de albaricoque (ASA) en la función cognitiva y la respuesta inflamatoria en un modelo de accidente cerebrovascular hemorrágico utilizando ratas Wistar, y examinar su correlación. Se asignaron aleatoriamente cincuenta ratas Wistar a cinco grupos: un grupo control, un grupo suplementado con ASA (que recibió 400 mg/kg de ASA), un grupo HC (con HC inducido) y grupos HC suplementados con 200 y 400 mg/kg de ASA, cada uno. La función cognitiva se evaluó mediante la prueba del laberinto eléctrico Y en estos grupos. Además, se utilizaron un ensayo inmunoabsorbente ligado a enzimas y una PCR en tiempo real para analizar los perfiles de expresión de proteínas y genes de factores inflamatorios y apoptóticos en el cerebro. En comparación con el grupo de control, las ratas del grupo HC tardaron más en dominar los criterios del laberinto (P<0,05). Además, el grupo HC exhibió niveles significativamente mayores de citocinas proinflamatorias interleucina-1β (IL-1β), IL-6 y factor de necrosis tumoral- α, y niveles reducidos de citocinas antiinflamatorias IL-4 e IL-10 en comparación al grupo control (P<0,05). Por el contrario, las ratas del grupo HC+400 mg/kg ASA mostraron tendencias opuestas en el tiempo de simulación eléctrica, la proteína del factor inflamatorio y el perfil de expresión génica (Bcl-2, BAX, Caspasa-3 y p53) en comparación con el grupo HC (P <0,05). Nuestros hallazgos sugieren que el extracto de ASA puede mejorar la disfunción cognitiva después de la HC en ratas, potencialmente mediante la modulación de factores inflamatorios secretados por la microglia.

Resumen Este estudio tuvo como objetivo determinar las concentraciones salivales de interleucina (IL)-1β, IL-2, IL-10, IL-23, factor de crecimiento transformante (TGF)-β y factor de necrosis tumoral (TNF)-α, nitrato (subproducto de la oxidación del óxido nítrico) y cortisol en pacientes con liquen plano oral (OLP). En este estudio transversal se incluyeron veinte pacientes diagnosticados con OLP y 20 voluntarios sanos (HV) del mismo sexo. Saliva entera no estimulada Se recolectó por la mañana, se determinaron las concentraciones de citocinas y cortisol en saliva mediante ensayo inmunoabsorbente ligado a enzimas (ELISA), se determinó nitrato mediante un analizador de óxido nítrico, se encontraron concentraciones salivales mayores de IL-2 (p<0,003), IL- 23 (p<0,04) y TGF-β (p=0,05) en pacientes con OLP en comparación con HV. No se encontraron diferencias significativas en los niveles salivales de TNF-α, IL-1β e IL-10. Las concentraciones de nitrato fueron marcadamente aumentó en pacientes con OLP (1227,0 ± 738,8 µM/mg de proteína total), en comparación con HV (261,6 ± 166,8 µM/mg; p<0,0001). Los niveles de cortisol salival también fueron más altos en los pacientes con OLP que en los controles (2,79 ± 1,39 vs. 1,94 ±1,21 ng/mg; p<0,048). Los niveles de óxido nítrico en saliva aumentaron notablemente en pacientes con OLP, lo que sugiere una relación de esta molécula con la muerte celular y el daño tisular observado en las lesiones de OLP.

Abstract This study aimed to determine salivary concentrations of interleukin (IL)-1β, IL-2, IL-10, IL- 23, transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, nitrate (a by-product of nitric oxide oxidation), and cortisol in patients with oral lichen planus (OLP). Twenty patients diagnosed with OLP and 20 sex-matched healthy volunteers (HV) were included in this cross-sectional study. Unstimulated whole saliva was collected in the morning. Salivary cytokine and cortisol concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Nitrate was measured in a nitric oxide analyzer. We found higher salivary concentrations of IL-2 (p<0.003), IL-23 ( p<0.04), and TGF-β (p=0.05) in patients with OLP compared to HV. No significant differences were found in salivary levels of TNF-α, IL-1β, or IL-10. Nitrate concentrations were markedly increased in OLP patients (1,227.0 ± 738.8 µM/mg total protein) when compared to HV (261.6 ± 166.8 µM/mg; p<0.0001). Salivary cortisol levels were also higher in OLP patients (2.79 ± 1.39 vs. 1.94 ±1.21 ng/mg; p<0.048). The markedly increased salivary levels of nitric oxide in patients with OLP suggest a relationship of this molecule with the cell death and tissue damage observed in these lesions.

Abstract Introduction : Chia and flax seeds are rich in alpha-linolenic acid (ALA), which is bioconverted into the active derivatives eicosapentaenoic (EPA) and doco sahexaenoic (DHA) having multiple beneficial effects. However, there is limited knowledge about the anti-inflammatory effects of chia and flax integral flours diets rich in ALA. Objective : The study aimed to evaluate the anti-inflammatory effect of dietary supplementation with integral chia and flax flours in a murine model of LPS-induced systemic inflammation. Methods : Balb/c mice were distributed into three groups: diet A (control), diet B (supplemented with inte gral chia flour), and diet C (supplemented with integral flax flour). Nutritional, hematological, and biochemical determinations were performed. ALA, EPA, and DHA were assessed by GC-MS in the liver, brain, cardiac and skeletal muscles. NF-kB immunoassays were per formed in kidney, liver, and peritoneal macrophages, respectively. The phagocytic capacity was determined in peritoneal macrophages and the expression of the pro- and anti-inflammatory cytokines was assessed by RT-qPCR in the kidney, liver, and spleen. Results : Diets B and C exhibited optimal nutritional adequacy and caused increased levels of ALA, EPA, and DHA in critical tissues compared to the control. The phagocytic capacity of murine peritoneal macrophages (p< 0.01) and IL-10 transcription increased, whereas the expression of NF-κB, IL-1β, IL-6, and TNF-α decreased in animals fed both experimental diets. Conclusions : This work contributes to the current knowledge of the anti-inflammatory effects of chia and flax integral flours rich in ALA and reinforces the health advantages of their consumption.

Resumen Introducción : Las semillas de chía y lino son ricas en ácido alfa-linolénico (ALA), sus derivados activos eico sapentaenoico (EPA) y docosahexaenoico (DHA) ejercen probados efectos beneficiosos. Existe un conocimiento limitado sobre los efectos protectores de ambas semillas bajo la forma de harinas integrales, siendo de particular interés el efecto antiinflamatorio. Objetivo : El objetivo de este trabajo fue evaluar el efecto antiinflamatorio de la suplementación dietaria con harinas integrales de semillas de chía y lino en un modelo murino de inflamación sistémica inducido por LPS. Métodos : Ratones de la cepa Balb/c fueron distribui dos en tres grupos: dieta A (control), dieta B (suplemen tada con harina integral de chía) y dieta C (suplementa da con harina integral de lino). Se efecturaron determi naciones nutricionales, hematológicas y bioquímicas. El contenido de ALA, EPA y DHA en hígado, cerebro, corazón y músculo esquelético se determinó por cromatografía GC-MS. Se realizó la inmunodetección de NF-kB en macrófagos peritoneales, riñón e hígado. Se determinó la capacidad fagocítica de macrófagos peritoneales y se evaluó la expresión de citoquinas pro y antiinflamatorias por RT-qPCR en riñón, hígado y bazo. Resultados : Las dietas B y C mostraron una adecua ción nutricional óptima y generaron niveles elevados de ALA, EPA y DHA en tejidos críticos. La capacidad fagocítica de los macrófagos peritoneales (p< 0.01) y la transcripción de IL-10 aumentó, mientras que la expre sión de NF-κB, IL-1β, IL-6 y TNF-α disminuyó en animales de los grupos B y C. Conclusiones : Este trabajo contribuye al conocimien to actual de los efectos antiinflamatorios de ambas hari nas integrales y refuerza los beneficios de su consumo.

Abstract Osteoarthritis (OA) can incapacitate the individual to perform their activities of daily living due to pain. This is an important public health issue that worsens worldwide and in Brazil, since the population goes through an aging process, and has caused increased public spending on the monitoring and maintenance of treatments that can last for years and still not be resolutive. Thus, the search for innovative and effective therapies that can reduce costs becomes necessary. In this context, the present study reports the first application of cell therapy with adipose-derived stem cells in the treatment of cases of OA that are refractory to the conservative treatment, performed in the Brazilian Unified Health System (Sistema Único de Saúde, SUS). The evaluation was performed with the application of the Visual Analog Scale (VAS), the Short Form Health Survey (SF-36) and the Western Ontario and McMaster Universities (WOMAC), specifics for OA evaluation, and also an analysis of the synovial fluid (inflammatory cytokines). The cell therapy improved the scores on the WOMAC, SF-36 and EVA, and reduced the inflammatory process. We observed a decrease of 0.73x in the TNF, of 0,71x in IL-1b, of 0,68x in IL-8, and of 0,70x in IL-10. For IL-6, an increase of 1,48x was observed. Therefore, this cell therapy can be considered promising in aiding the management of this disease, since it improved the patient's pain, decrease inflammatory markers, and enabled the return to activities of daily living, which resulted in an improvement in their quality of life. (OA pain Brazil process resolutive Thus necessary context adiposederived adipose derived Sistema Saúde SUS. SUS . SUS) VAS, VAS , (VAS) SF36 SF 36 (SF-36 WOMAC (WOMAC) cytokines. cytokines cytokines) SF-3 EVA 073x x 0 73x TNF 071x 71x IL1b, IL1b ILb IL 1b, 1b b IL-1b 068x 68x IL8, IL8 8, 8 IL-8 070x 70x IL10. IL10 10. 10 IL-10 IL6, IL6 6, 6 IL-6 148x 1 48x Therefore disease patients patient s markers life (VAS SF3 3 (SF-3 (WOMAC SF- IL- IL1 IL-1 (SF- (SF

Resumo A osteoartrite (OA) pode deixar o indivíduo incapacitado para realizar suas atividades da vida diária devido ao quadro álgico. Essa é uma importante questão de saúde pública que se agrava no mundo inteiro e no Brasil, uma vez que a população passa pelo processo de envelhecimento, e isso causa um aumento nos gastos públicos com o acompanhamento e manutenção dos tratamentos que podem perdurar por anos e mesmo assim não serem resolutivos. Assim, torna-se necessária a busca por terapias inovadoras e eficazes que possam reduzir esses custos. Nesse contexto, o presente estudo relata a primeira aplicação de terapia celular com células-tronco mesenquimais do tecido adiposo no tratamento de OA refratária ao tratamento conservador realizada no Sistema Único de Saúde (SUS). Na avaliação, foram usados os instrumentos Escala Visual Analógica (EVA), os questionários de qualidade de vida Short Form Health Survey (SF-36) e Western Ontario and McMaster Universities (WOMAC), específicos para avaliação da OA, e fez-se uma análise do líquido sinovial (citocinas inflamatórias). A terapia celular melhorou as pontuações no WOMAC, SF-36, e EVA, e reduziu o processo inflamatório. Observou-se redução de 0,73 × do TNF, de 0,71 × da IL-1b, de 0,68 × da IL-8, e de 0,70 × da IL-10. Já para a IL-6, observou-se aumento de 1,48 ×. Portanto, considera-se este tipo de terapia celular promissora no auxílio do manejo desta doença, pois melhorou o quadro álgico do paciente, reduziu os marcadores inflamatórios, e possibilitou o retorno às atividades da vida diária, o que resultou em uma melhora de sua qualidade de vida. (OA Brasil envelhecimento resolutivos Assim tornase torna custos contexto célulastronco células tronco SUS. SUS . (SUS) EVA , (EVA) SF36 SF 36 (SF-36 WOMAC (WOMAC) fezse fez citocinas inflamatórias. inflamatórias inflamatórias) SF36, 36, SF-36 inflamatório Observouse Observou 073 0 73 0,7 TNF 071 71 IL1b, IL1b ILb IL 1b, 1b b IL-1b 068 68 0,6 IL8, IL8 8, 8 IL-8 070 70 IL10. IL10 10. 10 IL-10 IL6, IL6 6, 6 IL-6 observouse observou 148 1 48 1,4 Portanto considerase considera doença paciente inflamatórios (SUS (EVA SF3 3 (SF-3 (WOMAC SF-3 07 7 0, 06 IL- IL1 IL-1 14 4 1, (SF- SF- (SF

ABSTRACT POEMS syndrome is a multisystem disorder caused by a neoplasm of plasma cells. The acronym "POEMS" refers to some of its characteristics: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It's a rare condition, and available information has been presented as case series. Its exact incidence is unknown. The pathophysiology is not yet fully clear, but the role of proinflammatory cytokines and overproduction of vascular endothelial growth factor is recognized. Diagnosis is based on criteria defined by the International Myeloma Working Group. However, atypical cases that do not meet all the criteria have been described, in which observation is chosen until symptoms appear or empirical treatment is initiated based on symptomatic involvement. We describe a series of 2 cases of patients with POEMS syndrome studied and treated at Carlos Van Buren Hospital in Valparaíso, Chile. Both meet the criteria for diagnosis but with variable presentations due to different elements of the minor criteria. Large retrospective series report polyneuropathy as the most common finding. Additionally, they have monoclonal gammopathy of undetermined significance (GMSI). Both patients underwent the same therapy regimen with melphalan/dexamethasone. Nowadays, both patients are stable and undergoing outpatient monitoring.

RESUMEN El síndrome POEMS es un trastorno multisistémico debido a una neoplasia de células plasmáticas. El acrónimo POEMS, se refiere a algunas de sus características: polineuropatía, organomegalia, endocrinopatía, proteína monoclonal y cambios en la piel. Es una patología rara cuya información se ha obtenido a partir de series de casos. Su incidencia exacta es desconocida. La fisiopatología aún no es completamente clara, pero se reconoce el rol de citoquinas proinflamatorias y de la sobreproducción del factor de crecimiento endotelial vascular. El diagnóstico se realiza en base a los criterios definidos por el International Myeloma Working Group. No obstante, se han descrito casos atípicos que no cumplen todos los criterios donde se decide vigilar hasta que aparezcan o iniciar el tratamiento empírico según el compromiso sintomático. A continuación, se presenta una serie de 2 casos de pacientes con síndrome de POEMS estudiados y tratados en el Hospital Carlos Van Buren de Valparaíso, Chile. Ambos cumplen criterios para el diagnóstico, pero con presentaciones variables por los distintos elementos de los criterios menores. Las grandes series retrospectivas reportan la polineuropatía como el hallazgo más común. Además, poseen GMSI. Ambos pacientes se sometieron al mismo esquema de terapia con melfalán/dexametasona. Hoy en día ambos pacientes se encuentran estables, en controles ambulatorios.

ABSTRACT Introduction. The Toll-like receptor (TLR) interacting with the promastigote of Leishmania spp. determines the cellular activation pathway. Objective. To determine the transcriptional expression of TLR-3, TLR-4, TLR-9, IL-12 and TNF-α in macrophages infected with a native strain of L. braziliensis (Lbn). Materials and Methods. Identification of Lbn was performed by qPCR for kinetoplast DNA sequences. Mouse peritoneal macrophages were infected with promastigotes (MI) and nitric oxide (NO) production was measured; transcript levels for TLRs and cytokines were quantified by qRT-PCR. Results. Lbn showed 96% homology to L. braziliensis. High ON production was observed in IMs at 2 h; significant transcriptional expression especially of TLR-3 and TLR-9, which corresponded with expression for cytokines. Conclusions. Lbn strongly activated macrophages via endosomal TLRs, which can be applied in the design of agonists to treat the disease.

RESUMEN Introducción. El receptor de tipo Toll (TLR) que interactúe con el promastigote de Leishmania spp. determina la vía de activación celular. Objetivo. Identificar la expresión transcripcional de TLR-3, TLR-4, TLR-9, IL-12 y TNF-α en macrófagos infectados con una cepa nativa de L. braziliensis (Lbn). Métodos. La identificación de Lbn se hizo empleando qPCR para secuencias del DNA del cinetoplasto. Los macrófagos peritoneales de ratones fueron infectados con promastigotes y se midieron la producción de óxido nítrico (ON). Se cuantificaron los niveles transcripcionales para TLRs y citoquinas empleando qRT-PCR. Resultados. Lbn presentó 96% de homología con L. braziliensis. En los infectados con promastigotes se observó elevada producción de ON a las 2 h; significativa expresión transcripcional especialmente de TLR-3 y TLR-9 que se correspondió con la expresión para citoquinas. Conclusión. Lbn activó fuertemente a los macrófagos mediante los TLRs endosomales lo cual puede ser aplicado en el diseño de agonistas para tratar la enfermedad.

SARS-CoV-2, which caused the coronavirus pandemic in 2019 (COVID-19), is a beta-coronavirus, and its infection in host cells can activate innate and adaptive immune responses through the activation of several pro-inflammatory cytokines. Thus, in this study we established the relationship between the severity and immunopathology of COVID-19 through the main inflammatory cytokines. Results show that tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukins (IL), such as IL-6, are stimulated by the activation of T cell subsets, which results in immune-mediated cellular destruction. Several cytokines reduce the immune response and predispose to a pro-inflammatory and auto-reactive state, including IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, and associated inflammatory markers (LDH, GM-CSF and VEGF). These higher cytokine levels end up favoring tissue damage in multiple systems, including lungs, heart, gastrointestinal, brain, kidneys and other organs. Increasingly, a greater impact of the markers IL-6, ferritin, pro-calcitonin, lactic dehydrogenase, D-dimer and hypoalbuminemia was observed in patients with severe infection of the disease. In general, the data analyzed confirmed that COVID-19 severity is not caused simply by the viral infection, but rather by immune response and aberrant inflammation. In this way, this study allows a contribution to clinical practice, and it shows that it is essential to carry out in-depth studies about the immunopathology of COVID-19, in order to determine the severity markers involved in the pathogenesis of the viral infection.

O SARS-CoV-2, causador da doença coronavírus 2019 (COVID-19), é um beta-coronavírus, e sua infecção nas células do hospedeiro pode ativar respostas imunes inata e adaptativa, por meio da secreção de várias citocinas pró-inflamatórias. Assim, estabelecemos neste estudo a correlação da gravidade e imunopatologia da COVID-19 com as principais citocinas inflamatórias. Resultados mostram que o fator de necrose tumoral alfa (TNF-α), interferon-gama (IFN-γ) e interleucinas (IL), como a IL-6, são estimulados pela ativação de subconjuntos de células T, o que resulta em destruição celular imunomediada. Sendo que, diversas citocinas deprimem a resposta imune sadia, e predispõem a um estado pró-inflamatório e auto-reativo, dentre elas, IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, e os marcadores inflamatórios associados (LDH, GM-CSF e VEGF). Isso acaba por favorecer danos teciduais em múltiplos sistemas, como no pulmonar, cardíaco, gastrointestinal, cerebral, renal, dentre outros. Acrescenta-se que foi observado um impacto maior dos marcadores IL-6, ferritina, pró-calcitonina, desidrogenase láctica, D-dímero e hipoalbuminemia em pacientes com infecção grave da doença. De forma geral, pela análise de dados, verificou-se que a gravidade da doença COVID-19 parece ser modulada não apenas pela infecção viral, mas também por respostas imunes e inflamatórias aberrantes no hospedeiro. Dessa forma, este estudo permite contribuir para o auxílio da prática clínica, sendo imprescindível a realização de estudos aprofundados acerca da imunopatologia da COVID-19, a fim de que se determine os marcadores de gravidade envolvidos na patogênese da infecção viral.

Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01–1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29–3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response. Background Realworld, Realworld Real world, world Real-world scarce Objective Th1Th17 ThTh Th1 Th17 Th Th1/Th1 Methods years interferonα, interferonα interferon α, α interferon-α factorα, factorα factor factor-α interleukin inter leukin IL2, IL2 IL 2, 2 (IL)-2 IL4, IL4 4, 4 IL-4 IL6, IL6 6, IL10, IL10 10, 10 IL-10 IL17A ILA 17A A array assessed HRs (HRs model Results 26 biologics HR 1.04 104 1 04 95 1.01–1.07 101107 01 07 0.012 0012 0 012 IL- 1.99 199 99 1.29–3.08 129308 29 3 08 0.002 0002 002 limitations evaluation Conclusions environment response Th1Th1 Th1/Th (IL)- IL1 IL-1 1.0 9 1.01–1.0 10110 0.01 001 1.9 19 1.29–3.0 12930 0.00 000 00 Th1Th (IL) 1. 1.01–1. 1011 0.0 1.29–3. 1293 (IL 1.01–1 101 0. 1.29–3 129 1.01– 1.29– 12 1.01 1.29 1.2

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely. Background CLE (CLE SLE. . Objective (SLE IHC (IHC assays Methods cytotoxic antiinflammatory anti biopsies 5 tumidus ACR82 ACR 82 (ACR-82 SLICC12 SLICC 12 (SLICC-12 systems Results CLESLE IL1β ILβ IL 1β β ARC82 ARC (ARC-82 0.024 0024 0 024 SLICC-12 0.0143 00143 0143 (ARC 0.0097 00097 0097 0.0148. 00148 0.0148 0148 0.0148) IL17 17 IL-1 0.0003 00003 0003 0.0351 00351 0351 Aand A FoxP3 FoxP 0.0257 00257 0257 0.0285 00285 0285 CD8 CD 0.0075 00075 0075 0.0102, 00102 0.0102 , 0102 0.0102) granulysinpositive granulysin 0.0024 00024 0.0116. 00116 0.0116 0116 0.0116) limitations group years Conclusions cohort IL1β, 1β, intensely ACR8 8 (ACR-8 SLICC1 1 (SLICC-1 ARC8 (ARC-8 0.02 002 02 SLICC-1 0.014 0014 014 0.009 0009 009 IL1 IL- 0.000 0000 000 0.035 0035 035 0.025 0025 025 0.028 0028 028 0.007 0007 007 0010 0.010 010 0.002 0002 0011 0.011 011 (ACR- (SLICC- (ARC- 0.0 00 SLICC- 0.01 001 01 0.00 0.03 003 03 (ACR (SLICC 0.

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. Background (MTX moderatesevere moderate severe AD. . (AD) Objective 2 weeks Methods singleinstitution single institution 1 15 (1 mgwk mg wk wks nonatopic non controls nonlesional pre IL31, IL31 IL 31, 31 IL31RA, IL31RA ILRA 31RA, 31RA RA OSMR TSLP Ki67 Ki IL4 4 IL- mRNA IL6, IL6 6, 6 IL-6 IL10, IL10 10, IL-10 TNFα, TNFα TNF α, α TNF-α IFNγ, IFNγ IFN γ, γ IFN-γ TARC CCL22. CCL22 CCL 22. 22 CCL-22 Results p 0.021, 0021 0.021 , 0 021 0.021) immunohistochemistry (immunohistochemistry 0.016 0016 016 IL-3 0.019 0019 019 postMTX identified limitations followup. followup follow up. up follow-up Conclusions pruritus IL31RA. 31RA. (AD ( IL3 3 Ki6 IL1 IL-1 CCL2 CCL-2 002 0.02 02 0.01 001 01 CCL- 00 0.0 0.

Abstract The clinical manifestations of cutaneous leishmaniasis (CL) depend not only on the infecting species involved, but also on the immune response of the individual. Although not yet well understood in humans, parasite survival and persistence are related to the cytokine profile and T cell proliferation, with the Th1 profile being related to cure, and the Th2 profile to disease progression. Considering the need for studies focused on the species with the highest circulation in the state of Amazonas, this study aimed to analyze the immunoregulation stimulated by soluble antigens (SLAs) of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis in human lymphocytes in vitro, in order to understand the immune response of patients with CL. Lymphoproliferation was evaluated against stimuli of SLAs from L. amazonensis (100 µg/mL), SLAs from L. guyanensis (100 µg/mL) and phytohemagglutinin (10 µg/mL) using a BrdU Cell Proliferation ELISA kit after 72 h of incubation. Quantification of the cytokines IL-1b, IL-6, IL-8, IL-10, IL-12 and TNF was performed using the BD™ cytometric bead array human Th1/Th2/Th17 cytokine kit. Our results demonstrated that soluble antigens from L. amazonensis and L. guyanensis stimulated the lymphoproliferation of PBMCs from patients primo-infected with CL. Among the cytokines dosed, the highest concentrations were of IL-6 and IL-8, thus demonstrating that the soluble antigens evaluated are capable of inducing regulatory mechanisms. CL (CL involved individual humans proliferation Th cure progression Amazonas (SLAs L (L. V. V (V. vitro 100 µg/mL, µgmL µg/mL , µg mL 10 (1 7 incubation IL1b, IL1b ILb IL 1b, 1b b IL-1b IL6, IL6 6, 6 IL8, IL8 8, 8 IL-8 IL10, IL10 10, IL-10 IL12 12 IL-1 BD Th1Th2Th17 ThThTh Th17 Th1/Th2/Th1 primoinfected primo infected dosed IL- mechanisms (L (V 1 ( IL1 Th1Th2Th1 Th1/Th2/Th Th1Th2Th

Resumo As manifestações clínicas da leishmaniose cutânea (LC) dependem não apenas da espécie infectante envolvida, mas também da resposta imune do indivíduo. Apesar de ainda não bem esclarecido em humanos, a sobrevivência e persistência do parasito estão relacionados ao perfil de citocinas e proliferação de células T, relacionando-se a cura ao perfil Th1, e a progressão da doença ao perfil Th2. Considerando a necessidade de estudos voltados para as espécies de maior circulação no estado do Amazonas, este trabalho teve como objetivo analisar a imunorregulação estimulada por antígenos solúveis (SLAs) de Leishmania (L.) amazonensis e Leishmania (V.) guyanensis em linfócitos humanos in vitro, afim de compreender a resposta imune de pacientes com LC. A linfoproliferação foi avaliada frente a estímulos de SLAs de L. amazonensis (100 μg/mL), SLAs de L. guyanensis (100 μg/mL) e Phytohemagglutinin (10 μg/mL) utilizando BrdU Cell Proliferation ELISA Kit após 72h de incubação. A quantificação das citocinas IL-1b, IL-6, IL-8, IL-10, IL-12 e TNF foi realizada por BD™ Cytometric Bead Array (CBA) Human Th1/Th2/Th17 Cytokine Kit. Nossos resultados demonstraram que os antígenos solúveis de L. amazonensis e L. guyanensis estimularam a linfoproliferação de PBMCs de pacientes primoinfectados com LC. Entre as citocinas dosadas, as de maiores concentrações foram de IL-6 e IL-8, demonstrando que os antígenos solúveis avaliados são capazes de induzir mecanismos regulatórios. LC (LC envolvida indivíduo T relacionandose relacionando se Th1 Th Th2 Amazonas (SLAs L (L. V. V (V. vitro 100 μg/mL, μgmL μg/mL , μg mL 10 (1 h incubação IL1b, IL1b ILb IL 1b, 1b b IL-1b IL6, IL6 6, 6 IL8, IL8 8, 8 IL-8 IL10, IL10 10, IL-10 IL12 12 IL-1 BD CBA (CBA Th1Th2Th17 ThThTh Th17 Th1/Th2/Th1 dosadas IL- regulatórios (L (V 1 ( IL1 Th1Th2Th1 Th1/Th2/Th Th1Th2Th

RESUMEN Introducción: El VIH/SIDA es considerado uno de los grandes casos de salud pública, sin embargo, está comprobado que pacientes que hacen uso de la terapia antirretroviral (TARV) y practican entrenamiento de fuerza provoca una promoción de su salud. Objetivos: Evaluar el impacto del entrenamiento de fuerza en la resistencia a las citoquinas y en la composición corporal de las personas que viven con VIH/SIDA. Métodos: Ensayo clínico aleatorizado, la muestra estuvo compuesta por 12 pacientes, siete del Grupo de Fuerza (TFG) y cinco del Grupo de Resistencia Muscular (GRM). Se compararon los niveles de las citocinas IL-2, IL-4, IL-6, IL-10 y TNF-α y la composición corporal en la primera y la última sesión. Los pacientes completaron 36 sesiones de entrenamiento de fuerza y resistencia durante 12 semanas. Resultados: Tras 36 sesiones de entrenamiento de resistencia GRM, se produjo un aumento significativo de 4.734 pg/mL a 5.050 pg/mL de IL-10 (p=0,002). En cuanto a la TFG, no se encontraron resultados significativos. En cuanto a la composición corporal, hubo diferencias significativas en la TFG debido al aumento de la masa magra en brazos de 6.441g a 7.014g (p=0,04), piernas de 16.379g a 17.281g (p=0,02) y cuerpo entero de 45.640g a 47.343g (p=0,01). En el GRM hubo una disminución significativa del porcentaje de grasa en los brazos de 23.160% a 20.750% (p = 0,04). Para la evaluación de la calidad de vida se utilizó el cuestionario WHOQOL-HIV-Bref, donde se encontró una mejoría significativa en todos los dominios, excepto en el dominio nivel de independencia. Conclusión: Concluimos que el entrenamiento de resistencia muscular es eficaz para aumentar la IL-10 y disminuir el porcentaje de grasa en los brazos, mientras que el entrenamiento de fuerza aumenta la masa magra total. Nivel de Evidencia I; Ensayo clínico aleatorizado. Introducción VIHSIDA VIH SIDA pública embargo TARV (TARV Objetivos Métodos aleatorizado 1 (TFG GRM. . (GRM) IL2, IL2 IL 2, 2 IL-2 IL4, IL4 4, 4 IL-4 IL6, IL6 6, 6 IL-6 IL10 10 IL-1 TNFα TNF α sesión 3 semanas Resultados 4734 734 4.73 pgmL pg mL 5050 5 050 5.05 p=0,002. p0002 p p=0,002 0 002 (p=0,002) significativos 6441g g 441g 7014g 7 014g p=0,04, p004 p=0,04 , 04 (p=0,04) 16379g 16 379g 17281g 17 281g p=0,02 p002 02 (p=0,02 45640g 45 640g 47343g 47 343g p=0,01. p001 p=0,01 01 (p=0,01) 23160 23 160 23.160 20750 20 750 20.750 0,04. 004 0,04 0,04) WHOQOLHIVBref, WHOQOLHIVBref WHOQOL HIV Bref, Bref WHOQOL-HIV-Bref dominios independencia Conclusión total I (GRM IL- IL1 473 73 4.7 505 05 5.0 p000 p=0,00 00 (p=0,002 p00 p=0,0 (p=0,04 (p=0,0 (p=0,01 2316 23.16 2075 75 20.75 0,0 4. 50 5. (p=0,00 p0 p=0, (p=0, 231 23.1 207 20.7 0, p=0 (p=0 23. 20. p= (p=

ABSTRACT Introduction: HIV/AIDS is considered one of the great cases of public health, but it is seen that patients who use antiretroviral therapy (ART) and practice strength training promote a promotion of their health. Objectives: Assess the impact of strength and resistance training on cytokines and body composition in people living with HIV/AIDS. Methods: Randomized clinical trial, the sample consisted of 12 patients, 7 from the Strength Group (GF) and 5 from Group 2, Muscular Resistance (MGR). We compared the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α cytokines and body composition in the first and last sessions. The patients completed 36 strength and resistance training sessions over 12 weeks. Results: After 36 sessions of GRM resistance training, there was a significant increase from 4,734 pg/mL to 5,050 pg/mL of IL-10 (p=0.002). Regarding the GFR, no significant results were found. For body composition, there were significant differences in GFR due to the increase in lean mass of the arms from 6,441g to 7,014g (p=0.04), legs from 16,379g to 17,281g (p=0.02) and whole body of 45,640g to 47,343g (p=0.01). In G2 there was a significant decrease in the percentage of fat in the arms from 23,160% to 20,750% (p = 0.04). To assess quality of life, the WHOQOL-HIV-Bref questionnaire was used, where significant improvement was found in all domains, except for the level of independence domain. Conclusion: We conclude that muscular resistance training is effective in increasing IL-10 and decreasing the percentage of fat in the arms, whereas strength training increases lean mass in arms, legs, and the whole body. Level of Evidence I; Randomized Clinical Trial. Introduction HIVAIDS HIV AIDS health ART (ART Objectives Methods trial 1 GF (GF 2 MGR. MGR . (MGR) IL2, IL2 IL IL-2 IL4, IL4 4, 4 IL-4 IL6, IL6 6, 6 IL-6 IL10 10 IL-1 TNFα TNF α 3 weeks Results 4734 734 4,73 pgmL pg mL 5050 050 5,05 p=0.002. p0002 p p=0.002 0 002 (p=0.002) 6441g g 441g 7014g 014g p=0.04, p004 p=0.04 , 04 (p=0.04) 16379g 16 379g 17281g 17 281g p=0.02 p002 02 (p=0.02 45640g 45 640g 47343g 47 343g p=0.01. p001 p=0.01 01 (p=0.01) G 23160 23 160 23,160 20750 20 750 20,750 0.04. 004 0.04 0.04) life WHOQOLHIVBref WHOQOL Bref used domains domain Conclusion I Trial (MGR IL- IL1 473 73 4,7 505 05 5,0 p000 p=0.00 00 (p=0.002 p00 p=0.0 (p=0.04 (p=0.0 (p=0.01 2316 23,16 2075 75 20,75 0.0 50 5, (p=0.00 p0 p=0. (p=0. 231 23,1 207 20,7 0. p=0 (p=0 23, 20, p= (p=

RESUMO Introdução: O HIV/AIDS é considerado um dos grandes casos de saúde pública, porém verifica-se que pacientes que fazem uso de terapia antirretroviral (TARV) e praticam treinamento de força provocam uma promoção de sua saúde. Objetivos: Avaliar o impacto do treinamento de força sobre a resistência nas citocinas e a composição corporal de pessoas vivendo com HIV/AIDS. Métodos: Ensaio clínico randomizado, a amostra foi composta por 12 pacientes, sendo sete do Grupo Força (TFG) e cinco do Grupo Resistência Muscular (GRM). Comparou-se os níveis das citocinas IL-2, IL-4, IL-6, IL-10 e TNF-α e a composição corporal na primeira e na última sessão. Os pacientes completaram 36 sessões de treinamento de força e resistência ao longo de 12 semanas. Resultados: Após 36 sessões de treinamento resistido GRM, houve um aumento significativo de 4.734 pg/mL para 5.050 pg/mL de IL-10 (p=0,002). Em relação à TFG, não foram encontrados resultados significativos. Para composição corporal, houve diferenças significativas na TFG devido ao aumento da massa magra dos braços de 6.441g para 7.014g (p=0,04), pernas de 16.379g para 17.281g (p=0,02) e corpo inteiro de 45.640g para 47.343g (p=0,01). No GRM houve diminuição significativa do percentual de gordura nos braços de 23.160% para 20.750% (p = 0,04). Para avaliação da qualidade de vida foi utilizado o questionário WHOQOL-HIV-Bref, onde foi encontrada uma melhora significativa em todos os domínios, exceto no domínio nível de independência. Conclusão: Conclui-se que o treinamento de resistência muscular é eficaz em aumentar a IL-10 e diminuir o percentual de gordura nos braços, enquanto o treinamento de força aumenta a massa magra geral. Nível de Evidência I; Ensaio Clínico Randomizado. Introdução HIVAIDS HIV AIDS pública verificase verifica se TARV (TARV Objetivos Métodos randomizado 1 (TFG GRM. . (GRM) Comparouse Comparou IL2, IL2 IL 2, 2 IL-2 IL4, IL4 4, 4 IL-4 IL6, IL6 6, 6 IL-6 IL10 10 IL-1 TNFα TNF α sessão 3 semanas Resultados 4734 734 4.73 pgmL pg mL 5050 5 050 5.05 p=0,002. p0002 p p=0,002 0 002 (p=0,002) significativos 6441g g 441g 7014g 7 014g p=0,04, p004 p=0,04 , 04 (p=0,04) 16379g 16 379g 17281g 17 281g p=0,02 p002 02 (p=0,02 45640g 45 640g 47343g 47 343g p=0,01. p001 p=0,01 01 (p=0,01) 23160 23 160 23.160 20750 20 750 20.750 0,04. 004 0,04 0,04) WHOQOLHIVBref, WHOQOLHIVBref WHOQOL Bref, Bref WHOQOL-HIV-Bref domínios independência Conclusão Concluise Conclui geral I Randomizado (GRM IL- IL1 473 73 4.7 505 05 5.0 p000 p=0,00 00 (p=0,002 p00 p=0,0 (p=0,04 (p=0,0 (p=0,01 2316 23.16 2075 75 20.75 0,0 4. 50 5. (p=0,00 p0 p=0, (p=0, 231 23.1 207 20.7 0, p=0 (p=0 23. 20. p= (p=

ABSTRACT Purpose: Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. Methods: RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. Results: Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1β, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1β and plasminogen activator inhibitor-1. Conclusions: Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway. Purpose esophagus antiinflammatory anti effects study Methods 2647 264 7 264. anesthesia junction 25, 25 (25 5 10 mg/kg mgkg mg kg 20 (2 mg/kg. . volume measured Additionally determined assessed Results factorα α TNFα, TNFα TNF , (TNF-α) IL1β, IL1β ILβ IL 1β, 1β β (IL)-1β IL6, IL6 6, 6 IL-6 cyclooxygenase2 cyclooxygenase 2 cyclooxygenase- COX2, COX2 COX (COX-2) iNOS (iNOS) PGE2. PGE2 PGE (PGE2) peroxidase iron calcium activity group malonaldehyde dismutase catalase viz viz. α, TNF-α IL10, IL10 10, IL-10 IL17, IL17 17, 17 IL-17 protein1 protein 1 protein-1 2, COX-2 NFκB. NFκB NF κB (NF-κB) P 0.001 0001 0 001 inhibitor1. inhibitor1 inhibitor 1. inhibitor-1 Conclusions pathway 26 ( (TNF-α IL- (COX-2 (iNOS (PGE2 IL1 IL-1 protein- COX- (NF-κB 0.00 000 00 inhibitor- (COX- (PGE 0.0 (COX 0.