Soro Bovino Fetal como fator de interferência na produção de citocinas por células-tronco de papila apical in vitro / Fetal bovine serum as an interference factor in cytokines production by stem cells from apical papilla in vitro

A endodontia e medicina regenerativa têm demonstrado grande interesse no potencial proliferativo e de diferenciação das Células-tronco de Papila Apical (SCAP), sendo que muitos estudos têm sido direcionados a avaliar as citocinas produzidas por tal população celular. No entanto, o suplemento mais comumente utilizado nos meios de cultura, o Soro Bovino Fetal (SBF), apresenta uma composição complexa e não totalmente conhecida, podendo interferir em diferentes fenômenos, sendo um deles a produção in vitro de citocinas pelas células. Portanto, este estudo teve como proposição: 1. avaliar a interferência do SBF na viabilidade celular das SCAP ativadas ou não por lipopolissacarídeo de Escherichia Coli (LPS) e 2. verificar a interferência de diferentes concentrações de SBF na produção das citocinas Interleucina (IL)-6, Fator de Crescimento Transformador (TGF)-1, Osteoprotegerina (OPG) e a quimiocina CCL2 no sobrenadante das SCAP ativadas por LPS. As células, previamente caracterizadas, obtidas do Biobanco da FOUSP, foram cultivadas em meio -MEM a 10% de SBF, plaqueadas e, após 24h, 48h, 72h, 7 e 14 dias de estímulo, foram então submetidas ao ensaio de MTT para a avaliação da viabilidade celular. A quantificação das citocinas foi realizada através do ensaio de imunoabsorção enzimática (ELISA), no tempo experimental de 24h. Os grupos foram organizados em triplicata de acordo com a concentração de SBF e presença ou não de LPS (1 g/mL). A análise estatística foi executada aplicando-se a análise de variância a dois critérios (two-way ANOVA) seguida de pós-teste de Tukey com nível de significância de 5%. Em 24h, as SCAP cultivadas em meio suplementado com qualquer concentração de SBF apresentaram maior metabolismo celular comparadas àquelas na ausência de soro. Para os tempos experimentais mais longos, de 7 e 14 dias, as SCAP ativadas por LPS mostraram um aumento significativo na viabilidade celular quanto cultivadas sob 10 e 15% de SBF. As duas concentrações testadas de SBF (1 e 10%) interferiram na produção de todas as citocinas avaliadas no presente estudo. Esse resultado enfatiza a importância de evitar a suplementação com SBF em estudos de detecção de citocinas envolvendo SCAP.

Evaluation of the immunomodulatory effect of Bougainvillea xbuttiana (Var. Orange) on the cytokine production induced by Botrhops jararaca venom in macrophages / Evaluación del efecto inmunomodulador de Bougainvillea xbuttiana (var. naranja) sobre la producción de citoquinas de macrófagos inducida pelo veneno de Bothrops jararaca

To study the effect of 50% ethanol extract of Bougainvillea xbuttiana on the enzymatic activity, cell via bility and cytokine production provoked by the venom of Bothrops jararaca in macro - phages. Three assays were used to study the effects of B. xbuttiana extract on the damage pro - duced by B. jararaca : Enzymatic activity was detected by measuring the proteoly tic and phos - pholipase A2; macrophages cytotoxicity was determined by the MTT method; levels of cytokine were evaluated using ELISA and a biological assay. After treatment with 300 µg/mL B. xbuttiana extract for 30 min, the proteolytic and phospholipase A2 activities of the venom were reduced to 95 and 61%, respectively. In macrophages cultures treated with B. xbuttiana extract combined with venom, the production of TNF - α, IL - 6 and IFN - γ was reduced, whereas IL - 10 was potenti - ated. Our results support the potential effect of the B. xbuttiana extract as a complementary therapy against the toxicity caused by the venom of B . jararaca snakes

Estudiar el efecto del extracto etanólico al 50% de Bougainvillea xbuttiana sobre la actividad enzimática viabilidad celular y producci ón de citoquinas provocada por el veneno de Bothrops jararaca en macrófagos Se utilizaron tres ensayos para estudiar los efectos del extracto de B. xbuttiana sobre el daño producido por B. jararaca : Se detectó actividad enzimática mediante la medición del proteolítico y fosfolipasa A2; la citotoxicidad de los macrófagos se determinó por el método MTT; Los niveles de citoquinas se evaluaron utilizando ELISA y un ensayo biológico. Después del tratamiento con 300 µg/mL de extracto de B. xbuttiana durante 30 mi n, las actividades proteolíticas y de fosfolipasa A2 del veneno se redujeron a 95 y 61%, respectivamente. En cultivos de macrófagos tratados con extracto de B. xbuttiana combinado con veneno, la producción de TNF - α, IL - 6 e IFN - γ se redujeron, mientras que IL - 10 se potenció. Nuestros resultados apoyan el efecto potencial del extracto de B. xbuttiana como terapia complementaria frente a la toxicidad provocada por el veneno de B. jararaca .

Produção de anticorpos e citocinas em resposta ao SARS-CoV-2: comparação entre imunidade vacinal e híbrida / Antibody and cytokine production in response to SARS-CoV-2: vaccine versus hybrid immunity comparison

A resposta imunológica pelo SARS-CoV-2 após protocolos vacinais e infecção natural é pouco compreendida. Comparando indivíduos vacinados com esquema heterólogo que receberam um reforço vacinal (imunidade vacinal) com aqueles que apresentaram episódio leve de COVID-19 (imunidade híbrida) no mesmo período, verificamos níveis semelhantes de anticorpos contra SARS-CoV-2. Em culturas de células mononucleares, o estímulo com o antígeno viral induziu produção de citocinas pró-inflamatórias nos dois grupos, entretanto, os níveis de IL-17 foram menores em indivíduos com imunidade vacinal. Nossos resultados sugerem que o reforço vacinal teve efeitos semelhantes à infecção natural pelo SARS-CoV-2 na resposta imunológica de indivíduos previamente vacinados. (AU)

The immune response generated by SARS-CoV-2 vaccination protocols and natural infection remains incompletely understood. We compared individuals who received a heterologous vaccination scheme with a booster shot (vaccine immunity) to those who experienced a mild COVID-19 episode (hybrid immunity) during the same timeframe. Our findings revealed similar levels of SARS-CoV-2 antibodies in both groups. Stimulation by viral antigen in mononuclear cell cultures induced pro-inflammatory cytokines in both groups, while individuals with vaccine immunity exhibited lower IL-17. These results suggest that a vaccine booster can induce an immune response in previously vaccinated individuals comparable to that elicited by natural SARS-CoV-2 infection. (AU)

Avanços no entendimento da patogenia da Covid-19: uma revisão / Advances in understanding Covid-19 pathogenesis: a review / Avances en la comprensión de la patogenia de la Covid-19: una revisión

Introdução: O SARS-CoV-2, causador da pandemia por Doença por Coronavirus 2019 (COVID-19) gerou desafios à saúde pública, principalmente pelo conhecimento escasso de sua patogênese, e de estratégias terapêuticas e preventivas eficazes. Diversas lacunas de conhecimento sobre a doença envolvem a contribuição de fatores de risco, as doenças concomitantes, os fatores genéticos e imunogenéticos, no direcionamento da resposta imune, bem como a hiperinflamação, a imunidade antiviral e os alelos dos antígenos leucocitários humanos (HLAs) dos pacientes, que estão relacionados ao desfecho da doença. Objetivo: Esta revisão integrativa objetivou aprofundar os conhecimentos sobre os mecanismos de imunidade relacionada aos fatores de risco, da hiperinflamação e da tempestade de citocinas decorrente da infecção por SARS-CoV-2, bem como os avanços de associação dos HLAs nos agravos da doença. Metodologia: A revisão integrativa foi realizada utilizando os descritores nas bases de dados PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, Portal periódicos CAPES e Open Journal System, sem limites de janela cronológica. Resultados: Os efeitos da pandemia e os esforços na busca do conhecimento sobre a patogênese da COVID-19 resultaram em avanço no combate da doença. Conseguiu-se relacionar fatores de risco como obesidade, hipertensão, diabetes, doenças renais crônicas, idade, gênero, e outras condições predisponentes ao agravo da doença. Sob o aspecto da patogênese, também houveram progressos no entendimento dos mecanismos celulares e humorais em resposta à doença, bem como conseguiu vincular a resposta da hiperinflamação e o perfil dos HLAs dos pacientes à evolução da doença ao óbito ou à convalescência. Conclusão: Os esforços científicos conjuntos e os avanços na compreensão dos mecanismos da doença conseguiram estabelecer estratégias de combate a COVID-19, resultando no fim da pandemia, porém ainda há avanços que devem ser alcançados para o combate das sequelas dos pacientes convalescentes e para minimização da COVID longa e seus prejuízos.

Introduction: SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has generated challenges to public health, mainly due to the limited knowledge of its pathogenesis and effective therapeutic and preventive strategies. Several gaps in knowledge about the disease involve the contribution of risk factors, concomitant diseases, genetic and immunogenetic factors, in directing the immune response, as well as hyperinflammation, antiviral immunity and human leukocyte antigen (HLAs) alleles of patients, which are related to the outcome of the disease. Aim: This integrative review aimed to deepen knowledge about the mechanisms of immunity related to risk factors, hyperinflammation and the cytokine storm resulting from SARS-CoV-2 infection, as well as advances in the association of HLAs in diseases. Methodology: The integrative review was carried out using the descriptors in the databases PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, CAPES periodical portal and Open Journal System, without chronological window limits. Results: The effects of the pandemic and efforts to seek knowledge about the pathogenesis of COVID-19 resulted in progress in combating the disease. It was possible to relate risk factors such as obesity, hypertension, diabetes, chronic kidney disease, age, gender, and other conditions predisposing to the worsening of the disease. From the aspect of pathogenesis, progress has also been made in understanding the cellular and humoral mechanisms in response to the disease, as well as linking the hyperinflammation response and the patients' HLA profile to the progression of the disease to death or convalescence. Conclusion: Joint scientific efforts and advances in understanding the mechanisms of the disease managed to establish strategies to combat COVID-19, resulting in the end of the pandemic, but there are still advances that must be achieved to combat the sequelae of convalescent patients and to minimize of long COVID and its losses.

Introducción: El SARS-CoV-2, causante de la pandemia de la Enfermedad del Coronavirus 2019 (COVID-19), ha generado desafíos a la salud pública, principalmente por el limitado conocimiento de su patogénesis y estrategias terapéuticas y preventivas efectivas. Varios vacíos en el conocimiento sobre la enfermedad involucran la contribución de factores de riesgo, enfermedades concomitantes, factores genéticos e inmunogenéticos, en la dirección de la respuesta inmune, así como la hiperinflamación, la inmunidad antiviral y los alelos del antígeno leucocitario humano (HLA) de los pacientes, que están relacionados con el resultado de la enfermedad. Objetivo: Esta revisión integradora tuvo como objetivo profundizar el conocimiento sobre los mecanismos de inmunidad relacionados con los factores de riesgo, la hiperinflamación y la tormenta de citocinas resultante de la infección por SARS-CoV-2, así como los avances en la asociación de los HLA en las complicaciones de la enfermedad. Metodología: La revisión integradora se realizó utilizando los descriptores de las bases de datos PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, portal periódico CAPES y Open Journal System, sin límites de ventana cronológica. Resultados: Los efectos de la pandemia y los esfuerzos por buscar conocimiento sobre la patogénesis de la COVID-19 resultaron en avances en el combate de la enfermedad. Se logró relacionar factores de riesgo como obesidad, hipertensión, diabetes, enfermedad renal crónica, edad, sexo y otras condiciones que predisponen al agravamiento de la enfermedad. Desde el punto de vista de la patogénesis, también se ha avanzado en la comprensión de los mecanismos celulares y humorales de respuesta a la enfermedad, así como en la vinculación de la respuesta de hiperinflamación y el perfil HLA de los pacientes con la progresión de la enfermedad hasta la muerte o la convalecencia. Conclusión: Los esfuerzos científicos conjuntos y los avances en la comprensión de los mecanismos de la enfermedad lograron establecer estrategias para combatir el COVID-19, teniendo como resultado el fin de la pandemia, pero aún quedan avances que se deben lograr para combatir las secuelas de los pacientes convalecientes y para Minimizar el COVID prolongado y sus pérdidas.

5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC

Purpose Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. Methods Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2­3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. Results There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. Conclusions Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H: quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase / 中国天然药物

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.

Research progress on immunological properties of ESAT-6 secreted by Mycobacterium tuberculosis and its role in new vaccines / 细胞与分子免疫学杂志

Early secreted antigenic target of 6 kDa protein (ESAT-6) is the major virulence factor of Mycobacterium tuberculosis (MTB), which can resist the clearance of MTB in bodies by inhibiting macrophage phagocytosis and autophagy reaction, thus impeding the immune defense function of the body against MTB infection. In addition, ESAT-6-induced apoptosis of macrophage and massive necrosis of innate immune cells can foster MTB proliferation and colonization, leading to systemic MTB infection. Moreover, ESAT-6 hampers the protective immune response of Th1 cells, reducing the secretion of pro-inflammatory cytokines and contributing to immune dysfunction, thus accelerating the course of MTB infection. During the process, the high immunogenicity of ESAT-6 can be leveraged as a dominant antigen in the development of new TB vaccines, making it a promising candidate with broad prospects for further development.

Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema / 中国修复重建外科杂志

OBJECTIVE@#To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema.@*METHODS@#The literature on stem cell-based treatments for lymphedema in recent years at home and abroad was extensively reviewed, and the animal studies and clinical trials on different types of stem cells for lymphedema were summarized.@*RESULTS@#Various types of stem cells have shown certain effects in animal studies and clinical trials on the treatment of lymphedema, mainly through local differentiation into lymphoid endothelial cells and paracrine cytokines with different functions. Current research focuses on two cell types, adipose derived stem cells and bone marrow mesenchymal stem cells, both of which have their own advantages and disadvantages, mainly reflected in the therapeutic effect of stem cells, the difficulty of obtaining stem cells and the content in vivo. In addition, stem cells can also play a synergistic role in combination with other treatments, such as conservative treatment, surgical intervention, cytokines, biological scaffolds, and so on. However, it is still limited to the basic research stage, and only a small number of studies have completed clinical trials.@*CONCLUSION@#Stem cells have great transformation potential in the treatment of lymphedema, but there is no unified standard in the selection of cell types, the amount of transplanted cells, and the timing of transplantation.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes / 中国结合医学杂志

OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles / Padrões inflamatórios sistêmicos em pacientes com câncer de ovário: Análise de citocinas, quimiocinas e micropartículas

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.

Essential oil of Cordia curassavica (Jacq) Roem. & Schult: in vitro and in silico evaluation of effects on dengue virus replication and cytokines production / Aceite esencial de Cordia curassavica (Jacq) Roem. & Schult: evaluación in vitro e in silico del efecto sobre la replicación del virus dengue y la producción de citoquinas

The lack of effective conventional therapie s against dengue has created an interest in herbal preparations as alternative therapies. In the present study, in vitro effects of Cordia curassavica essential oil (EO) on both dengue virus replication and cytokine production were examined. Predictions of molecular interactions between EO compounds and virus and cell proteins were performed with AutoDock Vina. The EO inhibited replication of dengue virus serotypes at IC 50 < 30 µg/mL, and it reduced 87% TNF - α, 67% IL - 8 and 46% IFN - α in LPS - stimulated PBMCs. The main EO compounds were trans - ß - caryophyllene (21.4%), germacrene D (17.8%), α - copaene (16.5%), trans - ß - guaiene (8.2%), and α - pinene (6.0%). The first two compounds, δ - cadinene, α - muurolene, α - cubebene and ß - burbonene were coupled to proteins involved in the TLR - 4 cytokine effector pathway. 3,7 - Guaiadiene was coupled to the viral E and C proteins. This study demonstrates the potential of C. curassavica EO as a starting point for discovering novel therapeutic for dengue.

La falta de terapias eficaces para el dengue ha suscitado interés por preparados herbales como terapias alternativas. En el presente estudio se examinaron efectos in vitro del aceite e sencial (AE) de Cordia curassavica sobre la replicación del virus dengue y producción de citoquinas. Se realizaron predicciones de interacciones moleculares entre los compuestos del AE y proteínas virales y celulares con AutoDock Vina. El AE inhibió la rep licación de serotipos del virus a CI 50 < 30 µg/mL y redujo 87% TNF - α, 67% IL - 8 y 46% IFN - α en MNCP. Los principales compuestos del AE fueron trans - ß - cariofileno, germacreno D, α - copaeno, trans - ß - guaieno y α - pineno. Los dos primeros compuestos, el δ - cadineno, el α - muuroleno, el α - cubebeno y el ß - burboneno se acoplaron a proteínas implicadas en la vía efectora de citoquinas TLR - 4. El 3,7 - guaiadiene se acopló a las proteínas virales E y C. Este estudio demuestra el potencial del AE de C. curassavica como punto de partida para descubrir nuevas tera pias para el dengue.

Correlation between inflammatory mediators and biochemical markers in patients with active pulmonary tuberculosis / Correlação entre mediadores inflamatórios e marcadores bioquímicos em pacientes com tuberculose pulmonar ativa

Objective: Correlate inflammatory mediators and biochemical parameters in patients with active pulmonary tuberculosis (TB) treated at a public hospital in São Luís, MA. Methods: This is a case-control study of patients with a positive diagnosis of active pulmonary TB. Serum samples from patients and the control group were collected for the clinical trials, and epidemiological data were collected through medical records and interviews. The control group consisted of healthy volunteers with no previous contact with TB cases, matched by age and sex to the clinical group. To measure inflammatory cytokines, we used the Human IL-6 ELISA Set and Human IFN-γ ELISA Set kits. Oxidative stress was measured by quantification of thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO). In biochemistry, the levels of uric acid, antistreptolysin "O" (AEO), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), calcium, total cholesterol, gamma-glutamyl transferase (Gamma GT), glucose, alkaline phosphatase, high-density lipoprotein (HDL), C-reactive protein (CRP) and triglycerides were measured. Results: The clinical group consisted of 53 patients. There was a substantial decrease in IFN-γ (p<0.0001) and a significant increase in IL-6 (p<0.0001). TBARS production increased significantly (p= 0.0414). There was no significant difference in NO production (p= 0.3194). In biochemistry, there was a significant increase in ALT (p= 0.0072), AST (p= 0.0016), Gamma GT (p= 0.0011), alkaline phosphatase (p<0.0001), CRP (p<0. .0001) and triglycerides (p= 0.0343), and a significant decrease in calcium (p<0.0001). A significant positive correlation was found between IL-6 and IFN-γ (p= 0.0448), as well as AST and ALT (p<0.0001); CRP and gamma GT (p<0.0001); Gamma GT and ALT (p= 0.0016); Gamma GT and AST (p=0.0004); triglycerides and cholesterol (p= 0.0002); alkaline phosphatase and gamma GT (p<0.0001); CRP and alkaline phosphatase (p<0.0001); triglycerides and calcium (p= 0.0121); cholesterol and calcium (p= 0.0261); glucose and cholesterol (p= 0.0373); and triglycerides and glucose (p= 0.0127) in biochemistry, with a significant negative correlation between glucose and uric acid (p= 0.0092); and CRP and HDL (p=0.0037). The correlation between inflammatory mediators and biochemical markers was positive between IL-6 and gamma GT (p= 0.0011); IL-6 and CRP (p<0.0001); IL-6 and alkaline phosphatase (p=0.0076); and NO and triglycerides (p= 0.0016), and significant negative correlation between IFN-γ and cholesterol (p= 0.0171) and TBARS and cholesterol (p= 0.0138). Conclusion: Immunosuppression of IFN-γ activity was observed. A correlation was found between IL-6 and inflammatory biochemical markers, indicating damage and injury caused by M. tuberculosis (AU).

Objetivo: Correlacionar mediadores inflamatórios e parâmetros bioquímicos em pacientes com tuberculose (TB) pulmonar ativa atendidos em um hospital público, em São Luís, MA. Métodos: Trata-se um caso-controle de pacientes com diagnóstico positivo para TB pulmonar ativa. Amostras de soro dos pacientes e grupo controle foram coletadas para os experimentos clínicos e os dados epidemiológicos foram coletados por meio de prontuários e entrevistas. O grupo controle foi formado por voluntários saudáveis sem contato prévio com casos de TB, pareados com idade e sexo ao grupo clínico. Para dosar citocinas inflamatórias, utilizaram-se os kits Human IL-6 ELISA Set e Human IFN-γ ELISA Set. Mediu-se o estresse oxidativo pela quantificação das espécies reativas do ácido tiobarbitúrico (TBARS) e óxido nítrico (ON). Na bioquímica, mediram-se os níveis de ácido úrico, anti-estreptolisina-O (AEO), alanina aminotransferase (ALT), amilase, aspartato aminotransferase (AST), cálcio, colesterol total, gama glutamil transferase (Gama GT), glicose, fosfatase alcalina, lipoproteína de alta densidade (HDL), proteína C reativa (PCR) e triglicerídeos. A análise estatística foi realizada pelo software Graph Pad Prism 8, com p<0,05 significativo. Re -sultados: O grupo clínico foi formado por 53 pacientes. Houve uma diminuição significativa de IFN-γ (p<0,0001), e aumento significativo de IL-6 (p<0,0001). A produção de TBARS aumentou significativamente (p= 0,0414). Não houve diferença significativa na produção de ON (p= 0,3194). Na bioquímica, houve aumento significativo em ALT (p= 0,0072), AST (p= 0,0016), gama GT (p= 0,0011), fosfatase alcalina (p<0,0001), PCR (p<0,0001) e triglice-rídeos (p= 0,0343), e diminuição significativa de cálcio (p<0,0001). Encontrou-se correlação positiva significativa entre IL-6 e IFN-γ (p= 0,0448), assim como AST e ALT (p<0,0001); PCR e gama GT (p<0,0001); gama GT e ALT (p= 0,0016); gama GT e AST (p= 0,0004); triglicerídeos e colesterol (p= 0,0002); fosfatase alcalina e gama GT (p<0,0001); PCR e fosfatase alcalina (p<0,0001); triglicerídeos e cálcio (p= 0,0121); colesterol e cálcio (p= 0,0261); glicose e colesterol (p= 0,0373); e triglicerídeos e glicose (p= 0,0127) na bioquímica, sendo negativa significativa entre glicose e ácido úrico (p= 0,0092); e PCR e HDL (p= 0,0037). A correlação entre marcadores infla-matório e bioquímicos foi positiva entre IL-6 e gama GT (p= 0,0011); IL-6 e PCR (p<0,0001); IL-6 e fosfatase alcalina (p= 0,0076); e ON e triglicerídeos (p= 0,0016), e negativa significativa entre IFN-γ e colesterol (p= 0,0171) e TBARS e colesterol (p= 0,0138). Conclusões: Observou-se imunossupressão da atividade de IFN-γ. Encontrou-se correlação entre IL-6 e marcadores bioquímicos inflamatórios, indicando dano e lesão causados por M. tuberculosis (AU).

Factor de crecimiento análogo a insulina-1 y cardiotrofina-1 inducido por ejercicio y su relación con hipertrofia miocárdica en maratonistas / Cardiotrophin-1 and Insulin like growth factor induced by exercise are associated to cardiac hypertrophy in marathon runners

Antecedentes: El ejercicio de alta intensidad induce hipertrofia miocárdica necesaria para adaptar al corazón a la mayor demanda de trabajo. Se desconoce si correr una maratón induce de forma aguda factores humorales asociados al desarrollo de hipertrofia miocárdica en atletas. Objetivo: Evaluar cardiotrofina-1 (CT1) y el factor de crecimiento análogo a insulina-1 (IGF-1), conocidos inductores de hipertrofia, en maratonistas previo y justo después de correr una maratón y su relación con hipertrofia cardíaca. Métodos: Estudio prospectivo ciego simple de atletas hombres que corrieron la maratón de Santiago. Se incluyó un grupo control sedentario. En todos los sujetos se realizó un ecocardiograma transtorácico estándar. Los niveles de CT1 e IGF-1 se determinaron en plasma obtenidos antes (basal) y justo después de haber terminado (antes de 15 minutos) la maratón, usando test de ELISA. Resultados: Los atletas tenían frecuencias cardíacas menores que los controles, asociado con una mayor hipertrofia miocárdica, determinado por el grosor del septo y pared posterior del corazón, y volúmenes del ventrículo y aurícula izquierda. Los niveles basales de CT1 e IGF-1 fueron similares entre atletas y controles sedentarios. El correr la maratón aumentó los niveles de estas dos hormonas en un subgrupo de atletas. Solo los atletas que incrementaron los niveles de IGF-1, pero no de CT1, tenían volúmenes de ventrículo izquierdo y derecho más grandes que los otros atletas. Conclusiones: IGF-1 que se incrementa de forma aguda por el ejercicio, pero no CT1, estaría asociado con el aumento de los volúmenes ventriculares observado en los atletas.

Background: High intensity exercise induces the development of myocardial hypertrophy necessary to adapt the heart to the increased work demand. Whether running a marathon is associated with acutely induced humoral factors responsible for the development of myocardial hypertrophy observed in athletes is not known. Objective: To evaluate the levels of cardiotrophin-1 (CT1) and insulin-like growth factor-1 (IGF-1), known hypertrophy inducers, in marathon runners before and just after running a marathon and their relationship with cardiac hypertrophy. Methodology: Single-blind prospective study of male athletes who ran the Santiago's marathon. A sedentary control group was included. All subjects underwent a standard transthoracic echocardiogram. CT1 and IGF-1 levels were determined in plasma obtained before (basal) and just after finishing (within 15 min) the marathon using ELISA assays. Results: Athletes had lower heart rates than controls, associated with greater myocardial hypertrophy, as determined by thickness of the heart's septum and posterior wall, and left atrial and ventricular volumes. Basal CT1 and IGF-1 levels were similar between athletes and sedentary controls. Marathon running increased the levels of these two hormones in a subgroup of athletes. Only the athletes who increased IGF-1 levels, but not CT1, had larger left and right ventricular volumes. Conclusion: IGF-1 acutely increased by exercise, but not CT1, was associated with the augmented ventricular volumes observed in athletes.

High-intensity interval training (treadmill) effects in myokines and endoplasmic reticulum stress of calf muscles in obese mice / Efectos del entrenamiento interválico de alta intensidad (trotadora) en miocinas y estrés del retículo endoplasmático de los músculos surales en ratones obesos

SUMMARY: Obesity is commonly associated with chronic tissue inflammation and skeletal muscle dysfunction. The study aimed to investigate the effects of High-Intensity Interval training (HIIT) on myokines and endoplasmic reticulum (ER) stress of diet- induced obese (DIO) mice. Three-month-old C57BL/6 male mice were fed a control (C) diet (n=20) or a high-fat (HF) diet (n=20) for 16 weeks. Then, half of the groups underwent HIIT (treadmill running) for an additional four weeks. HIIT increased calf muscles' contribution to BW (+24 %) and reduced weight gain in HF/HIIT than in HF (-120 %). Intramuscular fat accumulation was observed in HF and HF/ HIIT. Peak velocity was higher in HF/HIIT compared to HF (+26 %). Plasma insulin did not change, but glycemia was lower in HF/HIIT than in HF (-30 %). Fndc5 (+418 %) and Irisin (+72 %) were higher in HF/HIIT than in HF. Muscle Fgf21 was higher in HF/HIIT compared to HF (+30 %). In addition, NfKb (-53 %) and Tnfa (-63 %) were lower in HF/HIIT than in HF. However, Il1b (-86 %), Il6 (- 48 %), Il7 (-76 %), and Il15 (-21 %) were lower in HF/HIIT than in HF. Finally, HIIT reduced ER stress in HF/HIIT compared to HF: Atf4, -61 %; Chop, -61 %; Gadd45, -95 %. In conclusion, HIIT leads to weight loss and avoids muscle depletion. HIIT improves blood glucose, Irisin-Fndc5, and peak velocity. In addition, HIIT mitigates muscle inflammation and ER stress.

La obesidad es asociada comúnmente con inflamación tisular crónica y disfunción del músculo esquelético. El estudio tuvo como objetivo investigar los efectos del entrenamiento de intervalos de alta intensidad (HIIT) en las mioquinas y el estrés del retículo endoplásmico (ER) de ratones obesos inducidos por dieta (DIO). Se alimentó a ratones macho C57BL/6 de tres meses de edad con una dieta control (C) (n=20) o una dieta rica en grasas (HF) (n=20) durante 16 semanas. Luego, la mitad de los grupos se sometieron a HIIT (carrera en una trotadora) durante cuatro semanas más. HIIT aumentó la contribución de los músculos de la pantorrilla al BW (+24 %) y redujo el aumento de peso en HF/HIIT en HF (-120 %). Se observó acumulación de grasa intramuscular en HF y HF/HIIT. La velocidad máxima fue mayor en HF/HIIT en comparación con HF (+26 %). La insulina plasmática no cambió, pero la glucemia fue menor en HF/HIIT que en HF (-30 %). Fndc5 (+418 %) e Irisin (+72 %) fueron mayores en HF/HIIT que en HF. El Fgf21 muscular fue mayor en HF/ HIIT en comparación con HF (+30 %). Además, NfKb (-53 %) y Tnfa (-63 %) fueron menores en HF/HIIT que en HF. Sin embar- go, Il1b (-86 %), Il6 (-48 %), Il7 (-76 %) e Il15 (-21 %) fueron más bajos en HF/HIIT que en HF. Finalmente, HIIT redujo el estrés de RE en HF/HIIT en comparación con HF: Atf4, -61 %; Picar, - 61 %; Gadd45, -95 %. En conclusión, HIIT conduce a la pérdida de peso y evita el agotamiento muscular. HIIT mejora la glucosa en sangre, Irisin-Fndc5 y la velocidad máxima. Además, HIIT mitiga la inflamación muscular y el estrés ER.

Effect of a single resistance exercise session on inflammatory markers and oxidative stress in women living with HIV / Efeito de uma única sessão de exercício resistido sobre marcadores inflamatórios e estresse oxidativo em mulheres vivendo com hiv

ABSTRACT People living with HIV (PLH), who use antiretroviral therapy (ART), are more susceptible to changes in the inflammatory profile and oxidative stress, and women have greater access to ART. Although physical exercise is a complementary strategy to treatment due to its antioxidant and anti-inflammatory effects, it is not clear whether acute responses to exercise can be harmful to PLH. The aim of the study was to investigate the acute effect of resistance exercise (RE) on inflammatory and oxidative stress markers in PLH. Ten women, using ART, performed RE session consisting of seven exercises for the whole body. For biochemical evaluation, blood samples were collected before (pre), 1 hour (1h) and 2 hours (2h) after the RE session. One-way ANOVA followed by Bonferroni's post hoc test was used to compare results between time points. There was an increase only in markers, GSSG of 160% (pre: 0.40 ± 0.11; 1h: 1.18 ± 0.36; 2h: 1.04 ± 0.25 mmol/g), TNF-α of 98 % (pre: 4.60 ± 0.55; 1h: 6.95 ± 0.77; 2h: 9.10 ± 1.03 pg/ml) and 52% IL-6 (pre: 2.47 ± 0 .67; 1h: 3.63 ± 1.26; 2h: 5.38 ± 2.15 pg/ml). The other variables remained unchanged (P > 0.05). It is concluded that a RE session increased the levels of inflammatory markers and oxidative stress in PLH in a non-exacerbated way.

RESUMO Pessoas vivendo com HIV (PVH), que utilizam a terapia antirretroviral (TARV), são mais suscetíveis a alterações no perfil inflamatório e estresse oxidativo, sendo que as mulheres possuem maior acesso à TARV. Embora o exercício físico seja uma estratégia complementar ao tratamento devido aos seus efeitos antioxidantes e anti-inflamatórios, não está claro se as respostas agudas ao exercício podem ser prejudiciais às PVH. O objetivo do estudo foi investigar o efeito agudo de exercícios com pesos (EP) sobre marcadores inflamatórios e de estresse oxidativo em PVH. Dez mulheres, em uso da TARV, realizaram uma sessão de EP constituída por sete exercícios para o corpo todo. Para avaliação bioquímica, amostras de sangue foram coletadas antes (pré), 1 hora (1h) e 2 horas (2h) após a sessão de EP. A ANOVA one-way seguida do teste post hoc de Bonferroni foi utilizada para comparação dos resultados entre os momentos. Houve aumento apenas nos marcadores, GSSG de 160% (pré: 0,40 ± 0,11; 1h: 1,18 ± 0,36; 2h:1,04 ± 0,25 mmol/g), TNF-α de 98% (pré: 4,60 ± 0,55; 1h: 6,95 ± 0,77; 2h: 9,10 ± 1,03 pg/ml) e IL-6 de 52% (pré: 2,47 ± 0,67; 1h: 3,63 ± 1,26; 2h: 5,38 ± 2,15 pg/ml). As demais variáveis permaneceram sem alterações (P > 0,05). Conclui-se que uma sessão de EP aumentou os níveis de marcadores inflamatórios e estresse oxidativo em PVH de forma não exacerbada.

TNF-alpha and IL-17 cytokine levels in Brazilian patients with ankylosing spondylitis after anti-TNF therapy

Abstract The aim of this study was to evaluate tumor necrosis factor alpha (TNF-α), interleukin (IL)- 17A/F levels in the serum of ankylosing spondylitis (AS) patients after anti-TNF therapy, in order to understand how these cytokines are involved in this therapeutic response. Forty-four AS patients were included in the study: thirty using anti-TNF therapy were classified according to their therapy response as responders (15) and non-responders (15) and 14 without anti-TNF therapy were classified as AS control. Fifteen healthy individuals formed the control group. Serum levels of TNF-α were determined using Luminex technology and for IL-17A and IL-17F using ELISA. The non-responder patients presented higher serum levels of TNF-α than the responders and AS control; the same results were found when HLA-B*27 positive or negative patients were separately analyzed. IL-17A and IL17F serum levels were similar for all groups. According to the clinical disease activity, AS patients with BASDAI ≥4 had higher serum levels of TNF-α than AS patients with BASDAI <4. Positive correlation was found between TNF-α levels and BASDAI. In AS patients, TNF-α serum levels were associated with anti-TNF therapy and disease activity independently of HLA-B*27, and IL-17A and IL-17F were not related to anti-TNF treatment

Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of dental hypofunctional condition / A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes em hipofunção

Objetivo: Evidências científicas sugerem que a deficiência de estrógeno e fatores genéticos influenciam o desenvolvimento do sistema estomatognático. Este estudo teve como objetivo avaliar a influência da deficiência de estrógeno na expressão gênica de TNF-α, IL-1ß, IL-6 e IL-10 durante o desenvolvimento dentário em modelo murino. Material e Métodos: Ratas Wistar Hannover foram divididas em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo - cirurgia de ovariectomia e Grupo Controle - cirurgia fictícia. Para avaliar o desenvolvimento dentário, o incisivo inferior foi escolhido. O modelo de hipofunção dos incisivos inferiores foi realizado por ajuste incisal. O incisivo homólogo exercia hiperfunção dentária. Os animais foram avaliados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão gênica do TNF-α, IL-1ß, IL-6 e IL-10 na região odontogênica dos incisivos por meio de PCR em tempo real. Foi realizado o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: Houve diferenças estatisticamente significativas na expressão gênica de TNF-α e IL-1ß entre os grupos hipoestrogenismo e controle sob condição de hipofunção dentária (p=0,0084, p=0,0072, respectivamente). Conclusão: A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes hipofuncionais (AU)

Objective: Scientific evidence suggests that estrogen deficiency and genetic factors have an influence on the development of the stomatognathic system. This study aimed to evaluate the influence of estrogen deficiency on the gene expression of TNF-α, IL-1ß, IL-6 and IL-10 during dental development in a murine model. Material and Methods: Wistar Hannover rats were divided into two groups according to the intervention received: Hypoestrogenism Group - ovariectomy surgery and Control Group - fictitious surgery. To evaluate the dental development, the lower incisor was chosen. The mandibular incisor hypofunction model was performed by incisal adjustment. The homologous incisor exerted a hyperfunction. The animals were evaluated throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the gene expression of the TNF-α, IL-1ß, IL-6 and IL-10 in the odontogenic region of the incisors through real time PCR. Kruskal-Wallis test and Dunn's posttest were performed. The level of significance was 5%. Results: There were statistically significant differences of TNF-α and IL-1ß gene expression between the hypoestrogenism and control groups under hypofunction condition (p=0.0084, p=0.0072, respectively). Conclusion: Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of the hypofunctional teeth. (AU)

Effect of combined sedation using multiple drugs on inflammatory cytokines in patients with acute respiratory distress syndrome

Abstract he innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS

Insights on the role of cytokines in carious lesions / Insights sobre o papel das citocinas em lesões cariosas

Objetivo: A resposta imune da dentina-polpa à patogênese da cárie ainda é pouco compreendida devido à complexa interação dos processos envolvidos. O objetivo desta revisão foi explorar o papel das citocinas e sua relevância na patogênese da cárie dental. Resultados: A cárie dentária pode resultar em uma resposta inflamatória do hospedeiro na polpa dental, caracterizada pelo acúmulo de células inflamatórias levando à liberação de citocinas inflamatórias como, Interleucina-4 (IL-4), Interleucina (IL-6), Interleucina-8 (IL-8) e fator de necrose tumoral­α(TNF-α). IL-4 parece estar correlacionada com a profundidade das lesões cariosas; IL-6 está fortemente correlacionada com a doença cárie e é considerada um potente biomarcador; IL-8 pode ser um potente biomarcador tanto para cárie quanto para outras alterações presentes na polpa e sua liberação está correlacionada com TNF-α e IL-6; TNF-α desempenha um papel importante não apenas na progressão da cárie, mas também em outros processos patológicos. Conclusao: Mediadores específicos têm um grande potencial para servir como biomarcadores quanto à presença e progressão da doença cárie, o que incita a necessidade de mais investigações nesse campo (AU).

Objectives: The dentin-pulp immune response to caries pathogenesis is still poorly understood due to the complex interplay of the involving processes. The aim of this review was to explore the role of cytokines and its relevance in the pathogenesis of dental caries. Results: Dental caries can result in a host inflammatory response in the dental pulp, characterized by the accumulation of inflammatory cells leading to the release of inflammatory cytokines such as Interleukin-4 (IL-4), Interleukin (IL-6), Interleukin-8 (IL-8) and Tumor necrosis factor­ α (TNF- α ). IL-4 seems to be correlated to the depth of carious lesions; IL-6 is strongly correlated to caries disease and is considered a potent biomarker; IL-8 can be a potent biomarker for both caries and other changes present in the pulp and, its release is correlated to TNF- α and IL-6; TNF-α plays an important role not only in caries progression, but also in other pathological processes. Conclusion: Specific mediators have a great potential to serve as biomarkers alluding to the presence and progress of caries disease, urging further investigations in the field (AU)

The perspectives of biologics in the treatment of chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Chronic rhinosinusitis with nasal polyps （CRSwNP） remains the most difficult-to-treat subtype in the world. Biologics have shown positive results, especially in reducing nasal polyp size and improving patient-reported outcomes. The development of biologics has the potential to fulfill the unmet medical needs of treatment.