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Arch. argent. pediatr ; 120(4): 274-280, Agosto 2022. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1373104


El parto prematuro, la cesárea, el uso de antibióticos y la lactancia materna limitada son señalados como responsables en parte del aumento de enfermedades crónicas no transmisibles en niños, como las alergias, principalmente la alergia a la proteína de la leche de vaca (APLV). Quienes desarrollan enfermedades alérgicas muestran diferencias en la composición de su microbiota intestinal durante los primeros meses de vida, en comparación con los que no lo hacen. Las intervenciones tempranas para modular la microbiota intestinal y el sistema inmunológico pueden ser herramientas claves para el abordaje y tratamiento de la APLV. El criterio clínico y el trabajo interdisciplinario de alergólogos, gastroenterólogos, inmunólogos, microbiólogos y nutricionistas le permitirá al pediatra lograr un adecuado diagnóstico y un tratamiento oportuno. En este contexto, el empleo de bióticos (prebióticos, probióticos, sinbióticos y posbióticos) como herramientas nutricionales complementarias tiene un presente con sustento científico y un futuro promisorio para la prevención y tratamiento de estas patologías.

Preterm birth, C-section, antibiotic use, and limited breastfeeding are blamed in part for the increasing incidence of chronic noncommunicable diseases among children, such as allergies, mainly cow's milk protein allergy (CMPA). Those who develop allergic diseases, against those who do not, show differences in the composition of their gut microbiota during the first months of life. Early interventions to modulate the intestinal microbiota and the immune system may be the key tools for the management of CMPA. Clinical judgment and the interdisciplinary work of allergists, gastroenterologists, immunologists, microbiologists, and nutritionists will allow pediatricians to achieve an adequate diagnosis and a timely treatment. In this setting, the use of biotics (prebiotics, probiotics, synbiotics, and postbiotics) as supplementary dietary tools is scientifically supported at present and seems to be very promising for the prevention and treatment of these conditions.

Humans , Animals , Infant, Newborn , Milk Hypersensitivity , Probiotics/therapeutic use , Premature Birth , Food Hypersensitivity/diagnosis , Food Hypersensitivity/therapy , Cattle , Immunomodulation
Article in Chinese | WPRIM | ID: wpr-931686


Objective:To investigate the effects of miR-363-5p on the proliferation and apoptosis of nasopharyngeal carcinoma cells and the possible mechanism.Methods:miR-363-5p expression in human normal nasopharyngeal epithelial cells NP-69 and nasopharyngeal carcinoma cells 5-8F was detected using quantitative real-time polymerase chain reaction. Proliferation and apoptosis of 5-8F cells overexpresing miR-365-5p were determined. At the same time, Caspase3 and BRD4 protein expression in 5-8F cells were also detected.Results:miR-365-5p expression in 5-8F cells (0.71 ± 0.45) was significantly lower than that in NP-69 cells ( t = 2.68, P < 0.05). After overexpressing miR-363-5p, the proliferation of 5-8F cells was significantly decreased ( F = 22.68, P < 0.05). The apoptotic rate in the 5-8F cells was significantly higher than that in the control group [(24.45 ± 5.38)% vs. (18.23 ± 2.41)%, t = 4.13, P < 0.05]. Bax and Caspase3 protein levels in the 5-8F cells were (1.35 ± 0.24) and (1.44 ± 0.34) respectively, which were significantly higher than those in the NP-69 cells [(1.00 ± 0.08), (1.00 ± 0.23), t = 3.12, 5.12, P < 0.05]. BRD4 protein level in the 5-8F cells was significantly lower than that in the control group [(0.42 ± 0.24) vs. (1.00 ± 0.37), t = 2.98, P <0.05]. Conclusion:miR-365-5p can inhibit proliferation of nasopharyngeal carcinoma cells and promote their apoptosis. The negative regulatory effects of miR-363-5p on tumor cells are achieved possibly through inhibiting BRD4 protein expression.

Article in Chinese | WPRIM | ID: wpr-931635


Objective:To investigate the effectiveness and safety of docetaxel combined with cisplatin in the second-line treatment of advanced non-small cell lung cancer in older adult patients.Methods:120 older adult patients with advanced non-small cell lung cancer who received second-line treatment in Jiaozhou People's Hospital from January 2017 to December 2019 were included in this study. They were randomly assigned to undergo treatment with docetaxel (control group, n = 60) or docetaxel + cisplatin (observation group, n = 60). Clinical efficacy and complications were compared between the two groups. Results:After chemotherapy, short-term total response rate was significantly higher in the observation group than in the control group [70.00% (42/60) vs. 33.33% (20/60), χ2 = 16.15, P < 0.05]. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, cytokeratin 19-fragment CYFRA21-1 were (22.57 ± 3.22) μg/L, (48.61 ± 5.42) U/mL, (10.61 ± 1.64) μg/L, respectively in the observation group, which were significantly lower than those in the control group [(35.52 ± 4.46) μg/L, (69.64 ± 7.75) U/mL, (14.26 ± 1.95) μg/L, t = 18.23, 17.22, 11.09, all P < 0.001]. The percentages of CD 3+ and CD 4+ cells were (78.31 ± 8.09)% and (48.63 ± 5.74)%, respectively in the observation group, which were significantly higher than those in the control group [(69.58 ± 7.26)%, (39.82 ± 4.25)%, t = -6.22, -9.55, both P < 0.001]. The percentage of CD 8+ was significantly lower in the observation group than in the control group [(22.64 ± 3.82)% vs. (26.77 ± 4.01)%, t = 5.77, P < 0.001). The 1-year survival was significantly higher in the observation group than in the control group ( χ2 = 4.05, P < 0.05). There was no significant difference in the incidence of adverse reactions during chemotherapy between the two groups ( P > 0.05). Conclusion:Docetaxel combined with cisplatin is highly effective on advanced non-small cell lung cancer in older adult patients. The combined therapy can decrease serum tumor marker levels, improve immune function, and increase 1-year survival rate. It is safe and provides reliable efficacy and thereby is worthy of clinical promotion.

Article in Chinese | WPRIM | ID: wpr-931229


The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has caused a devastating health crisis worldwide.In this review,we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic.The following evidence supports our argu-ment.First,nuclear factor erythroid-derived 2-like 2(NRF2)agonists abrogate replication of SARS-CoV-2 in lung cells,and quercetin is a potent NRF2 agonist.Second,quercetin exerts antiviral activity against several zoonotic coronaviruses,including SARS-CoV-2,mainly by inhibiting the entry of virions into host cells.Third,inflammatory pathways activated by nuclear factor kappa B,inflammasome,and interleukin-6 signals elicit cytokine release syndrome that promotes acute respiratory distress syndrome in patients with COVID-19,and quercetin inhibits these pro-inflammatory signals.Fourth,patients with COVID-19 develop thrombosis,and quercetin mitigates coagulation abnormalities by inhibiting plasma protein disulfide isomerase.This review provides a strong rationale for testing quercetin for the management of COVID-19.

Article in English | WPRIM | ID: wpr-939914


Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 μmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

Animals , Cell Differentiation , Humans , Hydrogen Peroxide/metabolism , Mesenchymal Stem Cells , Oxidative Stress , Rats , Saponins , Umbilical Cord/metabolism
Journal of Clinical Hepatology ; (12): 1148-1151, 2022.
Article in Chinese | WPRIM | ID: wpr-924796


Interleukin-35 (IL-35) is an immunosuppressive cytokine mainly secreted by regulatory T cells and regulatory B cells and is involved in the pathogenesis of infectious diseases, tumors, and autoimmune diseases. This article summarizes the immunoregulatory role and mechanism of IL-35 in hepatitis B, liver cirrhosis, liver failure, and hepatocellular carcinoma caused by hepatitis B virus (HBV) infection. The analysis shows that IL-35 is a "double-edged sword" in HBV-related diseases, and it can not only promote the chronicity of infection and the progression of hepatocellular carcinoma, but also alleviate liver inflammation and inhibit liver fibrosis.

Acta Pharmaceutica Sinica ; (12): 296-302, 2022.
Article in Chinese | WPRIM | ID: wpr-922938


Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.

Braz. j. biol ; 82: e236297, 2022. tab, graf
Article in English | LILACS | ID: biblio-1153472


Abstract Plectranthus barbatus Andrews (Lamiaceae) is widely distributed in the world and has a range of popular therapeutic indications. This work aimed to evaluate the phytochemical characterization of two leaf extracts of P. barbatus, and their antimicrobial, antineoplastic and immunomodulatory potential. After collection, herborization and obtainment of the P. barbatus aqueous extract (PBA) and acetone:water 7:3 P. barbatus organic extract (PBO), the phytochemical characterization was performed by high-performance liquid chromatography (HPLC). The antimicrobial activity was performed to determine the minimum inhibitory concentration (MIC) against eight bacterial strains using the microdilution test and the fungus Trichophyton rubrum by disc diffusion assay and microdilution test. Cytotoxicity was assessed by MTT and trypan blue methods in normal peripheral blood mononuclear cells (PBMCs) at concentrations ranged between 0.1 to 100 µg.mL-1 and in neoplastic cell lines Toledo, K562, DU-145 and PANC-1 at 1, 10 and 100 µg.mL-1 . Immunomodulatory activity, was evaluated by sandwich ELISA of proinflammatory cytokines at BALB/c mice splenocytes cultures supernatant. Both extracts presented flavonoids, cinnamic derivatives, steroids and ellagic acid. PBO showed bacteriostatic activity against Acinetobacter baumannii (MIC = 250 µg.mL-1) clinical isolate and PBA fungistatic activity against Trichophyton rubrum (MIC = 800 µg.mL-1). The extracts did not exhibit toxicity to PBMCs and neoplastic cells (IC50 > 100 µg.mL-1). Additionally, PBO at 100 µg.mL-1 significantly inhibited IFN-γ and IL-17A cytokines (p = 0.03). Plectranthus barbatus is a potential candidate for therapeutic use due to its low toxicity in healthy human cells and exhibits biological activities of medical interest as bacteriostatic, fungistatic and immunomodulatory.

Resumo Plectranthus barbatus Andrews (Lamiaceae) é amplamente distribuída no mundo e com uma série de indicações terapêuticas populares. Este trabalho teve como objetivo avaliar a caracterização fitoquímica de dois extratos da folha de P. barbatus e seu potencial antimicrobiano, antineoplásico e imunomodulador. Após coleta, herborização e obtenção do extrato aquoso (PBA) e acetona: água 7: 3 (orgânico) (PBO) de P. barbatus, a caracterização fitoquímica foi realizada por cromatografia líquida de alta eficiência (CLAE). A atividade antimicrobiana foi realizada para determinar a concentração inibitória mínima (CIM) contra oito cepas bacterianas usando o teste de microdiluição e o fungo Trichophyton rubrum por ensaio de difusão em disco e teste de microdiluição. A citotoxicidade foi avaliada por métodos MTT e azul de tripan em células normais mononucleares do sangue periférico (CMSP) em concentrações variadas entre 0,1 a 100 µg.mL-1 e nas linhagens celulares neoplásicas Toledo, K562, DU-145 e PANC-1 em 1, 10 e 100 µg.mL-1 . A atividade imunomoduladora foi avaliada por ELISA sanduíche de citocinas pró-inflamatórias em sobrenadante de culturas de esplenócitos de camundongos BALB/c. Ambos os extratos apresentaram flavonoides, derivados cinâmicos, esteróides e ácido elágico. O PBO mostrou atividade bacteriostática contra Acinetobacter baumannii (CIM = 250 µg.mL-1) e atividade fungistática do PBA contra Trichophyton rubrum (CIM = 800 µg.mL-1). Os extratos não apresentaram toxicidade para CMSP e células neoplásicas (IC50 > 100 µg.mL-1). Além disso, o PBO a 100 µg.mL-1 inibiu significativamente as citocinas IFN-γ e IL-17A (p = 0,03). Plectranthus barbatus é um candidato potencial para uso terapêutico devido à sua baixa toxicidade em células humanas saudáveis ​​e exibe atividade de interesse médico como bacteriostática, fungistática e imunomoduladora.

Animals , Rabbits , Plectranthus , Leukocytes, Mononuclear , Plant Extracts/pharmacology , Microbial Sensitivity Tests , Arthrodermataceae , Phytochemicals/pharmacology , Mice, Inbred BALB C
Einstein (Säo Paulo) ; 20: eRB5954, 2022. tab
Article in English | LILACS | ID: biblio-1364790


ABSTRACT Despite advances in understanding of carcinogenesis and of treatment of acute myeloid leukemia, this neoplasm still has a lethality of at least 30%. The search for biomarkers that can predict the response to treatment in the early stages of the disease is still necessary. In recent years, a new form of cellular communication between tumor and non-neoplastic cells has been discovered: the exchange of information through extracellular vesicles. These are small vesicles released by membrane-coated cells that carry proteins, lipids, messenger RNAs, microRNA and DNA, which can be internalized and promote biological changes in target cells. Exosomes are qualified as a type of extracellular vesicle and, in tumors, carry immunoinhibitory signals that promote the escape of immune control. Recent studies have showed their involvement in communication with the cells of the tumor microenvironment and with chemoresistance in several tumors. To date, there is no information about immunoregulatory microRNAs transported by exosomes and their correlation with clinical evolution during chemotherapy for acute myeloid leukemia. Knowledge about immunomodulatory microRNAs obtained by leukemic cells and transported by exosomes can direct us towards the design of new diagnostic and treatment tools in this type of leukemia.

Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , MicroRNAs/metabolism , Exosomes/genetics , Exosomes/metabolism , Biomarkers , Cell Communication , Tumor Microenvironment/genetics
São Paulo; s.n; s.n; 2022. 136 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1392190


Introdução: A aterosclerose é uma doença inflamatória crônica decorrente de alterações na parede das artérias de médio e grande calibre e associadas a diversos fatores de risco, dentre os quais destaca-se as hiperlipidemias, ou seja, o aumento plasmático das lipoproteínas, mas também outras comorbidades, como a Síndrome Metabólica. Entre as lipoproteínas, a lipoproteína de baixa densidade (LDL) é de grande relevância na aterosclerose. Diferentes espécies de LDL modificada (LDLm) são originadas através de lipólise, glicação e proteólise, além da oxidação, variando em densidade e eletronegatividade, sendo melhor denominada LDL eletronegativa [LDL (-)]. Considerando as diferenças conformacionais entre a estrutura da ApoB-100 da LDL nativa e da LDL (-), em um estudo inicial, nosso grupo desenvolveu um anticorpo monoclonal (2C7) a partir da imunização de camundongos Balb/c com a LDL (-) humana. Em uma etapa seguinte foi mapeado o epítopo reconhecido pelo anticorpo monoclonal anti-LDL (-) através de phage display. O peptídeo ligante do anticorpo monoclonal anti-LDL (-) foi nomeado p2C7. Esse peptídeo não representa regiões da sequência linear da ApoB-100 humana, mas microdomínios conformacionais de epítopos da ApoB-100 da LDL (-), tornando-os candidatos para a imunomodulação da aterogênese. Portanto, investigar a imunomodulação induzida pelos peptídeo p2C7 miméticos da LDL (-), por representar um epítopo imunodominante da LDL (-), poderá abrir novas perspectivas terapêuticas futuras para a imunomodulação da aterosclerose. Objetivo: Avaliar a imunomodulação promovida pelo p2C7 in vivo, utilizando camundongos C57BL/6 LDLr -/- e amostras de plasma humano. Adicionalmente, no estágio (BEPE) realizado no Instituto Karolinska (dezembro de 2019 a março de 2021), investigou-se o imunometabolismo como mediador nas doenças cardiovasculares. Na parte II-A, estão descritos os resultados do estudo inicialmente proposto. Na parte II-B, apresenta-se os resultados que foram desenvolvidos posteriormente, com ampliação do escopo do projeto, abordando-se a inflamação vascular envolvida no aneurisma de aorta abdominal através de ferramentas de bioinformática. Na parte II-C, são apresentados os resultados do estudo do envolvimento da enzima indolamina 2,3 dioxigenase (IDO) na esteatohepatite não-alcoólica (NASH) e aterosclerose em camundongos ApoE-/- and ApoE/IDO/double-knockout. Metodologia: Foi avaliada a presença de anticorpos anti-p2C7 em amostras de plasma humano de indivíduos com ou sem síndrome metabólica. Realizamos a determinação de TNF circulante nas mesmas amostras e prosseguimos com regressões lineares associando os parâmetros inflamatórios com os níveis de anticorpos anti-p2C7. Camundongos C57BL/6 LDLr -/- foram imunizados com p2C7 e os adjuvantes Alum ou Montanide ISA 720, analisando-se os títulos de anticorpos contra p2C7 e LDL (-), a produção de citocinas (IL-10, IL-4, IL-2, IL-6, IFNγ, IL-17, TNFα) e células secretoras de anticorpos. Camundongos C57BL/6 LDLr -/- foram tolerizados contra os peptídeos mimotopos, com injeções intravenosas (veia caudal) e desafiados com a imunização contendo LDL (-) + Alum. Avaliou-se os títulos de anticorpos contra p2C7 e LDL (-) e a produção de citocinas (TNF-α, IFNγ, IL-12, IL-6, IL-10 e MCP-1). Os camundongos foram mantidos em dieta hipercolesterolêmica por 3 meses para formação da placa aterosclerótica. Após este período, os camundongos foram eutanasiados, avaliando-se a formação de placa aterosclerótica na artéria abdominal e arco aórtico, assim como a produção de citocinas (TNF-α, IFNγ, IL-12, IL-6, IL-10 e MCP-1). Camundongos C57BL/6 LDLr -/- foram imunizados com OVA-p2C7 e, após dieta hipercolesterolêmica de 3 meses para formação de placa aterosclerótica, foram avaliados os parâmetros inflamatórios e avaliada a captação de 18F-FDG no arco aórtico através de PET/CT. Resultados: A imunização com o p2C7 (livre) não foi capaz de induzir resposta humoral, não se observando títulos detectáveis de anticorpos reativos à p2C7 ou LDL (-) em nenhum camundongo imunizado, assim como não foram detectadas células secretoras de anticorpos específicos para a LDL (-). O grupo imunizado com Alum ou Montanide + p2C7 teve aumento significativo na produção de TNF- quando comparado com os demais grupos. O protocolo de tolerização foi realizado com sucesso, visto que os camundongos tolerizados apresentaram títulos de anticorpos inferiores aos controles para o epítopo utilizado. Apenas os camundongos tolerizados com o p2C7 apresentaram aumento significativo na produção de IL-6, IL-12, IL-10, TNF-α, IFNγ e MCP 1 após dieta hipercolesterolêmica. A imunização ativa com OVA-p2C7 foi capaz de reduzir a produção de TNF induzida pela dieta hipercolesterolêmica, assim como reduzir a captação de 18F-FDG. Conclusão: o epítopo p2C7 é altamente expresso na LDL (-) de pacientes com maior risco cardiovascular. Além disso, a imunização ativa com p2C7 também se mostra uma ferramenta promissora para prevenir e regular a inflamação causada pela LDL (-) no curso da aterosclerose

Introduction: Atherosclerosis is a chronic inflammatory disease resulting from changes in the wall of medium and large-caliber arteries and associated with several risk factors, among which hyperlipidemias stand out, ie, the increase in plasma lipoproteins, but also other comorbidities, such as Metabolic Syndrome. Among the lipoproteins, low-density lipoprotein (LDL) is of great relevance in atherosclerosis. Different isoforms of modified LDL (LDLm) are originated through lipolysis, glycation and proteolysis, in addition to oxidation, varying in density and electronegativity, being better called electronegative LDL [LDL (-)]. Considering the conformational differences between the ApoB-100 structure of native LDL and LDL (-), in an initial study, our group developed a monoclonal antibody (2C7) from the immunization of Balb/c mice with human LDL (-). In a next step, the epitope recognized by the anti-LDL monoclonal antibody (-) was mapped using phage display. The binding peptide of anti-LDL monoclonal antibodies (-) was named p2C7. This peptide does not represent linear sequence regions of human ApoB-100, but conformational microdomains of LDL (-) ApoB-100 epitopes, making them candidates for the immunomodulation of atherogenesis. Therefore, investigating the immunomodulation induced by p2C7 peptide mimetics of LDL (-) as it represents an immunodominant epitope of LDL (-) could open new future therapeutic perspectives for the immunomodulation of atherosclerosis. Objective: To evaluate the immunomodulation promoted by p2C7 in vivo, using C57BL/6 LDLr -/- mice, and human plasma samples. In addition, in the internship (BEPE), held at the Karolinska Institute (December 2019 to March 2021), immunometabolism as a mediator of Cardiovascular Diseases was studied. In part II-A, the results of the initially proposed study are described. In part II-B, the results that were developed later are presented, expanding the scope of the project, approaching the vascular inflammation involved in the abdominal aortic aneurysm through bioinformatics tools. In part II-C, the results of the study of the involvement of the enzyme indoleamine 2,3 dioxygenase (IDO) in non-alcoholic steatohepatitis (NASH) and atherosclerosis in ApoE-/- and ApoE/IDO/double mice are presented -knockout. Methodology: The presence of anti-p2C7 antibodies in human plasma samples with or without Metabolic Syndrome was evaluated. We measured circulating TNF in the same samples and proceeded with linear regressions associating inflammatory parameters with levels of anti-p2C7 antibodies. C57BL/6 LDLr -/- mice were immunized with p2C7 and the adjuvants Alum or Montanide ISA 720, analyzing the antibody titers against p2C7 and LDL (-), the production of cytokines (IL-10, IL-4, IL -2, IL-6, IFNγ, IL-17, TNFα) and antibody-secreting cells. C57BL/6 LDLr -/- mice were tolerized against mimotope peptides with intravenous injections (caudal vein) and challenged with immunization containing LDL (-) + Alum. Antibody titers against p2C7 and LDL (-) and cytokine production (TNF-α, IFNγ, IL-12, IL-6, IL-10 and MCP-1) were evaluated. The mice were kept on a hypercholesterolemic diet for 3 months for atherosclerotic plaque formation. After this period, the mice were euthanized, evaluating the formation of atherosclerotic plaque in the abdominal artery and aortic arch, as well as the production of cytokines (TNF-α, IFNγ, IL-12, IL-6, IL-10 and MCP -1). C57BL/6 LDLr -/- mice were immunized with OVA-p2C7 and, after a 3-month hypercholesterolemic diet for atherosclerotic plaque formation, inflammatory parameters were evaluated and 18F-FDG uptake was evaluated by PET/CT. Results: Immunization with p2C7 (free) was not able to induce a humoral response, with no detectable titers of antibodies reactive to p2C7 or LDL (-) being observed in any immunized mouse, as well as no detectable antibody-secreting cells for the LDL (-). The group immunized with Alum or Montanide + p2C7 had a significant increase in TNF-α production when compared to the other groups. The tolerance protocol was successfully performed, as the tolerized mice had lower antibody titers than controls for the epitope used. Only mice tolerated with p2C7 showed a significant increase in the production of IL-6, IL-12, IL-10, TNF-α, IFNγ and MCP 1 after a hypercholesterolemic diet. Active immunization with OVA-p2C7 was able to reduce TNF production induced by the hypercholesterolemic diet, as well as to reduce 18F-FDG uptake. Conclusion: the p2C7 epitope is highly expressed in LDL (-) of patients with higher cardiovascular risk. Furthermore, active immunization with p2C7 is also a promising tool to prevent and regulate inflammation caused by LDL (-) in the course of atherosclerosis

Animals , Male , Female , Mice , Immunization/instrumentation , Atherosclerosis/pathology , Immunomodulation , Arteries/abnormalities , Cardiovascular Diseases/pathology , Risk Factors , Diet/classification , Indoleamine-Pyrrole 2,3,-Dioxygenase/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibody-Producing Cells/classification
Acta Pharmaceutica Sinica ; (12): 2068-2076, 2022.
Article in Chinese | WPRIM | ID: wpr-936557


This study evaluated the regulatory effect of curcumin on memory follicular T cells (mTf) in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice. Forty male leptin mutant (ob/ob) mice were randomly divided into control group, control + curcumin group, dextran sodium sulfate (DSS) group and DSS + curcumin group, with 10 mice in each group. Mice in the DSS group and the DSS + curcumin group were induced by DSS to establish chronic ulcerative colitis model, and mice in the control + curcumin group and the DSS + curcumin group were given curcumin (200 mg·kg-1·d-1) by intragastric administration. Mice were sacrificed under anesthesia, and colon mass index, colon length and other conditions were observed in each group. Pathological injury of colonic was performed after HE staining. The levels of memory follicular helper T cells (mTfh) and memory follicular regulatory T cells (mTfr) in spleen of mice were detected by flow cytometry. The expression levels of interleukin-10 (IL-10) and interleukin-17A (IL-17A) in colon tissue were detected by ELISA. The results showed that curcumin significantly increased the body weight and colon length of obese mice with colitis, and decreased the colon weight, colon mass index and pathological score (P < 0.05). Curcumin significantly reduced the levels of central memory follicular T cells (cmTf), mTfh1, mTfh17 cells and the content of pro-inflammatory cytokine IL-17A (P < 0.01). The levels of effector memory follicular T cells (emTf) and mTfr and the content of anti-inflammatory cytokine IL-10 were increased (P < 0.05, P < 0.01). Therefore, curcumin may treat colitis in obese mice by regulating the balance of mTf cell subsets.

Arq. bras. med. vet. zootec. (Online) ; 73(6): 1334-1345, Nov.-Dec. 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1355678


The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)

No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)

Animals , Mice , Thalidomide/analysis , Mammary Neoplasms, Animal/drug therapy , Macrophages/drug effects , Immunomodulation , Neoplasm Metastasis
Perspect. nutr. hum ; 23(2): 199-220, jul.-dic. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1375987


Resumen Antecedentes: los tratamientos con base en medicamentos contra la COVID-19 no han sido aprobados hasta la actualidad. La forma más efectiva de enfrentar este problema de salud pública es la prevención con una adecuada alimentación, medidas de higiene y protección. Los alimentos han sido históricamente utilizados por la población para mejorar su nutrición y complementar el tratamiento o prevención de enfermedades. Se conocen los diversos compuestos bioactivos de algunos alimentos, que en estudios experimentales demostraron su acción antiviral e inmunomoduladora. Objetivo: identificar los compuestos bioactivos o preparados de alimentos con potencial efecto inmunomodulador, inmunoestimulante y antiviral contra el coronavirus. Materiales y métodos: se realizó una búsqueda en Google Scholar, Scopus y en la Biblioteca Virtual de Salud en Bases de datos de Medicina Tradicional, Complementaria e Integrativa utilizando los términos food, immunomodulatory, immunostimulatory y antiviral en cuatro búsquedas sucesivas. Resultados: se obtuvieron 93 artículos y se identificó mayor evidencia sobre el efecto antiviral e inmunológico contra el coronavirus en nueve alimentos: Allium sativum, Cinnamomum zeylanicum, Citrus sinensis, Zingiber officinale, Vitis vinífera, Allium cepa, Curcuma longa, Punica granatum y Sambucus nigra. Los cuatro primeros mostraron actividad contra el SARS-CoV-2. Conclusiones: se evidenció el efecto inmunológico y antiviral contra el coronavirus de nueve alimentos; sin embargo, son estudios in silico e in vitro, por ello se requiere mayor investigación preclínica y clínica que lo confirmen.

Abstract Background: Up to date drug-based treatments for COVID-19 have not been approved. The most effective way to face this public health problem is prevention with adequate nutrition, hygiene, and protection measures. Food has historically been used by people to improve their nutrition and complement the treatment or prevention of diseases. The various bioactive compounds of some foods are known, which in experimental studies demonstrated their antiviral and immunomodulatory action. Objective: To identify bioactive compounds of foods or food preparations with potential immunomodulatory, immunostimulatory, and antiviral effects against coronavirus. Material and Methods: A search was carried out in Google Scholar, Scopus, and Virtual Health Library on Traditional Complementary and Integrative Medicine using the terms food, immunomodulatory, immunostimulatory, and antiviral in four successive searches. Results: 93 articles were obtained, and further evidence of antiviral and immunological effect against coronavirus was identified on nine foods: Allium sativum, Cinnamomum zeylanicum, Citrus sinensis, Zingiber officinale, Vitis vinifera, Allium cepa, Curcuma longa, Punica granatum, and Sambucus nigra. The first four of them showed activity against SARS-CoV-2. Conclusions: The immunological and antiviral effect against coronavirus of nine foods was evidenced; however, they are in silico and in vitro studies, therefore it is required further preclinical and clinical research to confirm this.

Antiviral Agents , Coronavirus
Int. j. high dilution res ; 20(2/3): 34-43, June 4, 2021.
Article in English | LILACS, HomeoIndex | ID: biblio-1396358


Natural killer (NK) cells are among the first in defense of the innate immune system by eliminating a variety of abnormal or stressed cells such as cancer cells or virus-infected cells. Individuals who exhibit low cytolytic NK cell activity are believed to be at higher risk of viral infection, tumorigenesis, and various other diseases of the immune system. Therefore, restoration of impaired NK cell function might be an essential step in immunostimulatory therapy of immunocompromised patients. Bacillus firmus is a non-pathogenic gram-positive bacterium of the environment, which possesses various immunomodulatory properties in vitro and in vivo. This retrospective study reports on the effect of B. firmus on the activity of NK cells in vitro. Basal cytolytic NK cell activity against tumor cells among peripheral blood mononuclear cells (PBMCs) of routine patients was determined in a standardized NK cell cytotoxicity assay. The impact of cultivation of PBMCs with B. firmus preparation Bacillus firmus e volumine ex muris cellulae (Bacillus firmus (evc)) 6x on tumor cell killing by NK cells was monitored in relation to basal NK cell activity. This study showed that stimulation of PBMCs with Bacillus firmus (evc) 6x in vitro led to a significant increase in NK cell function. Substantial improvement in cytolytic NK cell activity (more than 1.3-fold of basal activity) was much more pronounced for patients with compromised NK cell function. Due to its immunostimulatory mode of action, Bacillus firmus (evc) may be of particular importance in therapy of patients with NK cell deficiency.

Killer Cells, Natural , K562 Cells , Bacillus firmus/immunology
Hematol., Transfus. Cell Ther. (Impr.) ; 43(1): 58-64, Jan.-Mar. 2021. tab
Article in English | LILACS | ID: biblio-1154302


ABSTRACT Background: The allogeneic transfusion-related immunomodulation (TRIM) may be responsible for an increase in survival of renal transplants but in contrast it could increase the rate of bacterial infections or the recurrence rate of tumors post-operatively. Objective: This review focuses in the implications of perioperative allogeneic transfusions on the immune-inflammatory response of surgical transfused patients. Results: ABTs modify immune functions in recipients including decrease of the number of lymphocytes; decrease the CD4 cells; decrease the CD4/CD8 T-cell ratio; decrease NK cells; and decrease the lymphocyte response to mitogens. TRIM effects may be mediated by allogeneic white cells present in blood products; soluble peptides present in transfused plasma; and/or biologic mediators released into the supernatant of blood units. A recent systematic review and meta-analysis including 36 clinical observational studies (n = 174,036) concluded that perioperative ABTs not only decreased overall survival and reduced colorectal cancer-specific survival. Furthermore ABTs increased the rate of infectious, cardiac, pulmonary and anastomotic complications in colorectal cancer patients undergoing surgery. Conclusions: It has been demonstrated by laboratory tests that TRIM is associated with transfusion recipient immune alterations but its influence in colorectal cancer recurrence after resection remains controversial though may exist. Surgical techniques reducing intraoperative blood loss have limited the number of ABTs perioperatively, however increase in mortality continues to be reported in literature after ABT in colorectal cancer surgery. Poor survival associated to TRIM in colorectal cancer might be due to higher number of allogeneic transfused units and/or prolonged length of blood storage.

Humans , Transplantation, Homologous , Colorectal Neoplasms , Erythrocyte Transfusion , Immunomodulation , Immunity , Prognosis , Blood Transfusion
J. pediatr. (Rio J.) ; 97(1): 22-29, Jan.-Feb. 2021. graf
Article in English | LILACS | ID: biblio-1154718


Abstract Objective: To describe the effect of prednisolone on language in children with autism spectrum disorder. This study is based upon two hypotheses: autism etiology may be closely related to neuroinflammation; and, an effective treatment should restore the individual's language skills. Method: This is a prospective, double-blinded, randomized, placebo-controlled clinical trial, carried out in a federal university hospital. The initial patient sample consisted of 40 subjects, which were randomized into two parallel groups. Inclusion criteria were: male gender, 3-7 years of age, and meeting the Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) diagnostic criteria. The final sample consisted of 38 patients, of whom 20 were randomized to the placebo group and 18 to the active group. The latter received prednisolone for 24 weeks, at an initial dose of 1 mg/kg/day and a tapering dose from the ninth week onward. Language was measured on four occasions over a 12-month period by applying two Brazilian tools: the Language Development Assessment (ADL) and the Child Language Test in Phonology, Vocabulary, Fluency, and Pragmatics (ABFW). Results: The side effects were mild: two patients had hypertension, five had hyperglycemia, and two had varicella. Prednisolone increased the global ADL score in children younger than 5 years of age who had developmental regression (p = 0.0057). The ABFW's total of communicative acts also responded favorably in those participants with regression (p = 0.054). The ABFW's total of vocal acts showed the most significant results, especially in children younger than 5 years (p = 0.004, power = 0.913). Conclusions: The benefit of prednisolone for language scores was more evident in participants who were younger than five years, with a history of developmental regression, but the trial's low dose may have limited this benefit. The observed side effects do not contraindicate corticosteroid use in autism.

Humans , Male , Child , Autistic Disorder/complications , Autistic Disorder/drug therapy , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/drug therapy , Brazil , Prednisolone , Prospective Studies
Acta sci., Health sci ; 43: e52932, Feb.11, 2021.
Article in English | LILACS | ID: biblio-1368494


Unravelling the efficacy of gut biome has a major impact on health. An unbalanced microbiome composition is linked to many common illnesses such as gut dysbiosis, mental deformities and immunological imbalance. An optimistic influence on the gut biome can be made by consumingprobiotics. This would stimulate neuroprotection and immunomodulation intended by heavy metals pollution. Lead is a major source of neurotoxin that can induce neural deformities. Lactobacillusspecies isolated from curd were characterized to confirm its specificity. Zebra fish was reared at standard conditions and preclinical assessment on the intensity of induced neurotoxin lead was performed. The embryo toxic assay, immunomodulation effects and animal behavioural models endorsed the consequence of neurotoxicity. Different concentrations of bacterial isolate with standard antidepressant was considered for analysing the vigour of toxicity and its influence on cognitive behaviour by novel tank diving method. The restrain in the animal behaviour was also conferred by all the test samples with a decreased bottom dwelling time which was authenticated with haematology and histopathological studies. The alterations in morphology of the lymphocytes were balanced by the treated test samples. This study paves a twofold potential of probiotic as neuroprotectant and immune modulator against heavy metal toxicity.

Animals , Bacteria/pathogenicity , Zebrafish , Probiotics/analysis , Neuroprotection/immunology , Brain-Gut Axis/immunology , Lead/analysis , Bacteria/virology , Congenital Abnormalities/virology , Lymphocytes/microbiology , Metals, Heavy/analysis , Toxicity , Immunomodulation/immunology , Dysbiosis/microbiology , Lactobacillus/immunology
Braz. arch. biol. technol ; 64: e21200179, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153293


HIGHLIGHTS L. duriusculum n-BuOH extract reduces inflammatory responses both in vitro and in vivo. L. duriusculum n-BuOH extract inhibits NF-κB-dependent transcriptional responses. L. duriusculum n-BuOH extract decreases the expression of TNF-α and IL-6 genes.

Abstract Limonium duriusculum is used in folk medicine to treat inflammatory disorders and has gained attention due to its richness in apigenin. The present investigation was performed to evaluate and confirm its anti-inflammatory properties, in cell lines and animal models. The potential anti-inflammatory properties of n-butanol (n-BuOH) extract of L. duriusculum (BEL) and isolated apigenins were examined on NF-κB transcriptional activity in TNFα- or LPS-stimulated cells, and on in vivo acute inflammatory models (carrageenan induced paw edema and peritonitis). BEL treatment was able to inhibit the activity of an NF-κB reporter gene in HCT116 cells both in the absence and in the presence of exogenous TNFα, used as NF-κB pathway inducer. This anti-inflammatory effect was even more potent compared to Apigenin (APG1) and was confirmed using monocyte-derived THP-1 cells treated with LPS to stimulate NF-κB-dependent transcription of IL-6 and TNFα mRNAs. Apigenin7-O-β-(6''-methylglucuronide) (APG2) was instead inactive both in HCT116 and THP-1 cells. BEL (oral, 200 mg/kg) led to paw swelling inhibition, vascular permeability and peritoneal leukocyte and PN migration diminution. Apigenins (intraperitoneal, APG1, APG2: 20 mg/kg) also evoked a significant anti-edema effect, early vascular permeability and leukocyte influx reduction. Collectively, this study demonstrates for the first time the effectiveness of L. duriusculum to inhibit NF-κB-dependent transcriptional responses in HCT116 and THP-1 cells. In vivo studies also established that L. duriusculum possesses a potential anti-inflammatory effect, confirm its traditional, empirical use, that could be attributed to its richness in apigenin.

Humans , Animals , Male , Rats , Plant Extracts/pharmacology , Plumbaginaceae/chemistry , Immunomodulation/drug effects , Anti-Inflammatory Agents/pharmacology , Interleukin-6 , Rats, Wistar , Models, Animal , THP-1 Cells
São Paulo; s.n; s.n; 2021. 97 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1396743


Os polissacarídeos não amido constituem importante parcela das fibras dietéticas, e podem ser considerados modificadores de resposta biológica (MRBs), uma vez que são capazes de interagir com o sistema imune, e suas características estruturais estão atreladas aos efeitos biológicos gerados. O potencial imunomodulador dos polissacarídeos do chuchu já foi demonstrado, entretanto, informações sobre suas características estruturais e sua relação com o perfil imunológico são limitadas a ensaios in vitro, não havendo, até o momento, estudos in vivo. Assim, o objetivo do estudo foi avaliar, in vitro e in vivo, o perfil imunomodulador de frações isoladas do polissacarídeo do chuchu. Por meio da filtração tangencial foram obtidas as frações de estudo, SeRI<50 e SeSE<50, respectivamente as frações isoladas do polissacarídeo do chuchu extraídas do resíduo insolúvel e do sobrenadante pós-tratamento enzimático para retirada do amido com peso molecular menor que 50 kDa. A caracterização por meio da determinação da composição monossacarídica e da análise de ligação apontou que ambas as frações são formadas por galacturonanos, arabinanos, arabinogalactanos e glicomananos. A SeRI<50 é menos ramificada e, provavelmente, composta por galactanos, enquanto SeSE<50 é mais ramificada e, provavelmente, composta por galactuglucomananos. Essas frações foram capazes de estimular os macrófagos murinos RAW 264.7 e as células mononucleares do baço, do sangue e do intestino delgado de camundongos Balb/c, sugerindo um perfil de ação mais pró-inflamatório, com base nos efeitos produzidos pelas espécies reativas de oxigênio, citocinas e pelos marcadores de ativação de linfócitos. Ambas as amostras, SeRI<50 e SeSE<50, mostraram ser eficientes em ativar a cascata imunológica, não sendo citotóxicas mesmo com a maior concentração testada no ensaio in vitro

Non-starch polysaccharides are important components of dietary fibers, and they may be considered biological response modifiers (MRBs), as they may interact with the immune system, depending on their structural characteristics. The immunomodulatory potential of chayote polysaccharides has already been demonstrated, however, information on their structural characteristics and their relationship with the immunological profile are limited to in vitro assays, with no reports on in vivo studies. Thus, the objective of the study was to evaluate, in vitro and in vivo, the immunomodulatory profile of polysaccharide from chayote. Through tangential filtration two fractions, SeRI <50 and SeSE <50, were obtained, respectively the fraction isolated from the chayote polysaccharide extracted from the insoluble residue and the fraction from the enzymatic post-treatment supernatant to remove starch, both under molecular weight 50 kDa. The monosaccharide composition and linkage analysis showed that both fractions are formed by galacturonans, arabinans, arabinogalactans and glycomanans. SeRI <50 is less branched and probably composed of galactans, while SeSE <50 is more branched and probably composed of galactuglucomannans. These fractions were able to stimulate murine macrophages RAW 264.7 and mononuclear cells of the spleen, blood and small intestine of Balb / c mice, suggesting a more proinflammatory action profile, based on the reactive oxygen species production, cytokines and lymphocyte activation markers. Both samples, SeRI <50 and SeSE <50, were able to efficiently activate the immunological cascade, not being cytotoxic even at the highest concentration tested in the in vitro assay

Starch/adverse effects , Vegetables/classification , In Vitro Techniques/instrumentation , Lymphocyte Activation , Lymphocytes/classification , Cytokines/agonists , Immunomodulation , Immunologic Factors , Macrophages/classification
Rev. cuba. hematol. inmunol. hemoter ; 37(supl.1): e1473, 2021. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1351992


Introducción: La idea de exclusión competitiva es indiscutible cuando se trata de animales y bacterias que intentan ocupar el mismo nicho ecológico, pero su aplicación a la coinfección viral no es tan sencilla de interpretar. La interferencia viral es un fenómeno en el que un virus suprime competitivamente la replicación de otros virus coinfectantes y es el resultado más común de las coinfecciones virales. Objetivo: Comprender mejor el comportamiento de las infecciones respiratorias concomitantes en escenarios de brotes comunitarios y de forma individual en entornos hospitalarios e individuos con comorbilidades. Métodos: Se realizó una búsqueda de información en las bases de datos MEDLINE / PubMed, SciELO y LILACS. También se consideraron artículos publicados en el repositorio de preimpresión medRxiv y los informes de los Centros para el Control y Prevención de enfermedades de los Estados Unidos de América. Mediante el gestor de referencias Mendeley, se eliminaron los duplicados y aquellos que no se ajustaban al objetivo del estudio, seleccionando 48 artículos para la revisión. Análisis y síntesis de la in formación: En la literatura científica se encontró evidencia que sustenta la exclusión competitiva viral entre virus relacionados que comparten células susceptibles y permisivas. Conclusión: La exclusión competitiva impide que dos virus que comparten rutas de transmisión similares y el mismo órgano diana, infecten no sólo al mismo tiempo, sino que también se propaguen con éxito. Por lo tanto, la sindemia producida por virus que comparten estas características podría ser un evento improbable(AU)

Introduction: The idea of competitive exclusion is undisputed when it comes to animals and bacteria trying to occupy the same ecological niche, but its application to viral coinfection is not so simple to interpret. Viral interference is a phenomenon in which one virus competitively suppresses the replication of other co-infecting viruses and is the most common outcome of viral co-infections. Objective: To better understand the behavior of concomitant respiratory infections in community outbreak settings and individually in hospital settings and individuals with comorbidities. Methods: A search for information was performed in the MEDLINE / PubMed, SciELO and LILACS databases. Articles published in the preprint repository medRxiv and reports from the US Centers for Disease Control and Prevention were also considered. Using the Mendeley reference manager, duplicates and those that did not fit the study objective were eliminated, selecting 48 articles for the review. Analysis and synthesis of information: Evidence supporting viral competitive exclusion between related viruses sharing susceptible and permissive cells was found in the scientific literature. Conclusion: Competitive exclusion prevents two viruses that share similar transmission routes and the same target organ from infecting not only at the same time, but also from spreading successfully. Therefore, syndemia produced by viruses sharing these characteristics could be an unlikely event(AU)

Humans , Male , Female , Viral Interference , Disease Outbreaks , Coinfection , COVID-19/virology , Respiratory Tract Infections , Concurrent Symptoms , Competitive Behavior/drug effects