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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
Rev. bras. anal. clin ; 53(2): 127-130, 20210630.
Article in Portuguese | LILACS | ID: biblio-1348666


Até o presente momento, foram notificadas mais de 550 mil mortes causadas por COVID-19 no Brasil. Estimulada pelo SARS-Cov-2, a formação de um inflamassoma causa um processo inflamatório sistêmico, responsável pela progressão da enfermidade, e ainda favorece o surgimento de doenças oportunistas, como as parasitoses, que são excelentes moduladoras do sistema imunológico, induzindo uma tolerância do organismo através do equilíbrio entre as respostas pró-inflamatórias e anti-inflamatórias. A partir disso, um levantamento bibliográfico foi realizado com o objetivo de avaliar a possível relação imunomoduladora das infecções parasitárias na COVID-19. Há uma extensa discussão quanto à presença de parasitoses concomitantes a esta coronavirose, devido à possibilidade de modulação do sistema imunológico, que pode ser capaz de refrear ou intensificar a progressão da COVID-19, bem como interferir na soroconversão pós-vacina dos indivíduos afetados, uma vez que doenças diretamente relacionadas aos processos inflamatórios, como Diabetes mellitus do tipo 2, tornam estes indivíduos mais susceptíveis às formas mais graves desta pandemia. Sendo assim, ainda que alguns autores sugiram a possibilidade da helmintíase experimental como uma alternativa para a imunomodulação, trata-se de uma ideia controversa, que necessita de maiores estudos para avaliar se tal procedimento seria seguro e viável de ser aplicado ou não.

Until now, more than 550,000 deaths caused by COVID-19 have been reported in Brazil. Stimulated by Sars-Cov-2, the formation of an inflammasome causes a systemic inflammatory process, responsible for the progression of the disease, and favors the emergence of opportunistic diseases, such as parasitosis, which are excellent modulators of the immune system, inducing a tolerance of the organism through the balance between pro-inflammatory and anti-inflammatory responses. From this, a bibliographical survey was carried out with the aim of evaluating the possible immunomodulatory relationship of parasitic infections in COVID-19. There is an extensive discussion regarding the presence of parasitic diseases concomitant to this coronavirus, due to the possibility of modulation of the immune system, which may be able to curb or intensify the progression of COVID-19, as well as interfere with the post-vaccine seroconversion of affected individuals, a since diseases directly related to inflammatory processes, such as type 2 diabetes mellitus, make these individuals more susceptible to the more severe forms of this pandemic. Thus, although some authors suggest the possibility of experimental helminthiasis as an alternative to immunomodulation. This is a controversial idea, which needs further studies to assess whether such a procedure would be safe and viable to apply or not.

Parasitic Diseases , Opportunistic Infections , Immunomodulation , COVID-19
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
Chinese Medical Journal ; (24): 2700-2709, 2021.
Article in English | WPRIM | ID: wpr-921204


BACKGROUND@#There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.@*METHODS@#A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.@*RESULTS@#After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.@*CONCLUSION@#Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

Carcinoma, Non-Small-Cell Lung/surgery , Chemotherapy, Adjuvant , Humans , Immunomodulation , Lung Neoplasms/surgery , Neoplasm Staging , Propensity Score , Retrospective Studies , Thymalfasin
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
Rev. Assoc. Med. Bras. (1992) ; 66(6): 728-731, June 2020.
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1136289


SUMMARY Voluminous tumors represent a challenge in radiation oncology, particularly when surgical resection is not possible. Lattice radiotherapy (LTR) is a technique that may provide equivalent or superior clinical response in the management of large tumors while limiting toxicity to adjacent normal tissues. LRT can precisely deliver inhomogeneous high doses of radiation to different areas within the gross tumor volumes (GTV). The dosimetric characteristic of LTR is defined by the ratio of the valley dose (lower doses - cold spots) and the peak doses, also called vertex (higher doses - hot spots), or the valley-to-peak dose ratio. The valley-to-peak ratio thereby quantifies the degree of spatial fractionation. LRT delivers high doses of radiation without exceeding the tolerance of adjacent critical structures. Radiobiological experiments support the role of radiation-induced bystander effects, vascular alterations, and immunologic interactions in areas subject to low dose radiation. The technological advancements continue to expand in Radiation Oncology, bringing new safety opportunities of treatment for bulky lesions.

RESUMO Tumores volumosos representam um desafio para a radio-oncologia, em especial quando a ressecção cirúrgica não é possível. A radioterapia com técnica Latisse (LTR) pode gerar resposta clínica equivalente ou superior ao tratamento convencional de grandes tumores, limitando a toxicidade nos tecidos normais adjacentes. A LRT pode fornecer com precisão altas doses não homogêneas de radiação em diferentes áreas do volume tumoral (GTV). A característica dosimétrica da LTR é definida pela razão entre a dose na região do vale (doses mais baixas - pontos frios) e as doses de pico, também chamadas de vértice (doses mais altas - pontos quentes) ou a razão da dose vale/pico. Dessa forma, a razão vale/pico quantifica o grau de fracionamento espacial da entrega de dose. A LRT entrega, dessa forma, altas doses de radiação sem exceder a tolerância de estruturas críticas adjacentes. Experimentos radiobiológicos suportam o chamado "efeito espectador" induzido por radiação, o qual promove alterações vasculares e interações imunológicas, levando à resposta tumoral mesmo em áreas expostas a baixas doses de radiação. Os avanços tecnológicos continuam a se expandir na radio-oncologia, trazendo, por meio da LTR, uma nova oportunidade segura de tratamento para lesões volumosas.

Humans , Radiotherapy , Immunotherapy , Neoplasms/therapy , Radiation Injuries , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Dose Fractionation, Radiation , Immunomodulation
Article in English | WPRIM | ID: wpr-762180


PURPOSE: Allergen immunotherapy (AIT) induces immunological tolerance, and there is increasing evidence of the clinical efficacy of AIT in the treatment of allergic asthma. However, the optimal parameters for asthma control in clinical trials are still unclear. We investigated the efficacy of AIT with respect to changes in the inhaled corticosteroid (ICS) dose in patients with allergic asthma. METHODS: A total of 117 adults with allergic asthma who had used ICS for more than 1 year in a single tertiary hospital in Korea were included in this retrospective study. We compared the clinical parameters and outcomes between the AIT group (ICS with AIT, n = 48) and the non-AIT group (ICS without AIT, n = 69) by applying an inverse probability of treatment weighting method. The patients in the AIT group had received subcutaneous AIT monthly as a maintenance treatment for more than 1 year. The changes in the ICS dose from baseline were evaluated in the 2 groups for 3 years. RESULTS: The proportion of responders who discontinued or decreased in the ICS dose with achieving control status of asthma was significantly higher in the AIT group than in the non-AIT group throughout the study period (at 6 months, 52.1% vs. 24.6%; at 1 year, 70.8% vs. 34.7%; at 2 years, 89.5% vs. 35.6%; at 3 years, 96.3% vs. 51.2%). Treatment responses did not differ significantly by type of allergen (single- or multi-allergens or 3 different products) used throughout the study period. CONCLUSIONS: Irrespective of the type of allergen, long-term maintenance AIT helps to spare ICS dose and achieve better control in patients with allergic asthma in real-world clinical practice.

Adult , Asthma , Desensitization, Immunologic , Humans , Immunomodulation , Korea , Methods , Retrospective Studies , Tertiary Care Centers , Treatment Outcome
J. venom. anim. toxins incl. trop. dis ; 26: e20190093, 2020. ilus, tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1135141


Ventral root avulsion (VRA) is an experimental approach in which there is an abrupt separation of the motor roots from the surface of the spinal cord. As a result, most of the axotomized motoneurons degenerate by the second week after injury, and the significant loss of synapses and increased glial reaction triggers a chronic inflammatory state. Pharmacological treatment associated with root reimplantation is thought to overcome the degenerative effects of VRA. Therefore, treatment with dimethyl fumarate (DMF), a drug with neuroprotective and immunomodulatory effects, in combination with a heterologous fibrin sealant/biopolymer (FS), a biological glue, may improve the regenerative response. Methods: Adult female Lewis rats were subjected to VRA of L4-L6 roots followed by reimplantation and daily treatment with DMF for four weeks. Survival times were evaluated 1, 4 or 12 weeks after surgery. Neuronal survival assessed by Nissl staining, glial reactivity (anti-GFAP for astrocytes and anti-Iba-1 for microglia) and synapse preservation (anti-VGLUT1 for glutamatergic inputs and anti-GAD65 for GABAergic inputs) evaluated by immunofluorescence, gene expression (pro- and anti-inflammatory molecules) and motor function recovery were measured. Results: Treatment with DMF at a dose of 15 mg/kg was found to be neuroprotective and immunomodulatory because it preserved motoneurons and synapses and decreased astrogliosis and microglial reactions, as well as downregulated the expression of pro-inflammatory gene transcripts. Conclusion: The pharmacological benefit was further enhanced when associated with root reimplantation with FS, in which animals recovered at least 50% of motor function, showing the efficacy of employing multiple regenerative approaches following spinal cord root injury.(AU)

Animals , Biological Products , Biopolymers , Fibrin , Immunomodulation , Dimethyl Fumarate , Neuroprotection , Gene Expression
São Paulo; s.n; s.n; 2020. 107 p. graf.
Thesis in Portuguese | LILACS | ID: biblio-1292606


As pectinas presentes nas frutas, assim como sua versão modificada, estão entre as biomoléculas mais promissoras no campo da imunomodulação. Este estudo teve como objetivo avaliar o potencial imunomodulador de pectinas obtidas de goiabas verdes e maduras, bem como suas versões modificadas. As goiabas cv. Tailandesas foram avaliadas ao longo do amadurecimento, sendo acompanhadas as alterações da cor da polpa e casca, firmeza, produção de etileno e respiração, perda de massa e o teor de açúcares solúveis. Após a caracterização dos frutos, foram extraídas as pectinas e estas foram caracterizadas quanto ao conteúdo monossacarídico, peso molecular, presença de oligossacarídeos e grau de esterificação. As pectinas in natura de goiaba madura e verde, bem como a versão modificada desta última apresentaram frações de alto e baixo peso molecular, alta proporção de ácido galacturônico e alto teor de esterificação. Por outro lado, as pectinas modificadas derivadas de goiaba madura apresentaram maior desesterificação, com perda de frações de menor peso molecular, menor proporção de ácido galacturônico e baixo teor de esterificação. As pectinas foram incubadas com células THP-1 e RAW 264.7, e apesar da alta viabilidade celular e ausência de efeito citotóxico, resultou em expressiva produção de espécies reativas de oxigênio. De modo geral, as pectinas in natura de goiaba verde e madura, e pectina modificada de goiaba verde promoveram estímulo da produção de citocinas diversas, em especial inflamatórias, como IL-1ß, IL-12, CCL5, CXCL10 e CXCL9, para células THP-1 e IL-10 (antiinflamatória), TNF-α e MCP-1, demonstrando seu potencial imunomodulador, já para células RAW 264.7 as pectinas estimularam a produção de IL-10, TNF-α e MCP-1, demonstrando seu potencial imunomodulador. A pectina modificada derivada da goiaba madura não promoveu a indução significativa de nenhuma citocina. Estes resultados sugerem que as pectinas obtidas a partir de goiabas têm potencial imunomodulador e devem ser estudadas em outros modelos celulares e / ou em concentrações mais altas e modelos in vivo, para que esses benefícios possam realmente ser comprovados

The pectin present in fruits and their modified version are the most promising biomolecules in the immunomodulatory field. This study aimed to evaluate the immunomodulatory potential of pectins obtained from unripe and ripe guavas (Psidium guajava L.) cv. Thailandesa as well as their modified versions. The guavas were characterized during ripening regarding cell wall solubilization, sugar content, firmness, mass loss and ethylene production rate and respiration during 10th following harvest. After fruit characterization, pectins were extracted and characterized for monosaccharide content, molecular weight, presence of oligosaccharides and degree of esterification. Pectins from unripe and ripe guava as well as the modified versions of pectins had high and low molecular weight fractions, a high proportion of galacturonic acid and high esterification content. On the other hand, modified pectins derived from ripe guava showed higher de-esterification, with loss of lower molecular weight fractions, a lower proportion of galacturonic acid and low esterification content. The pectins were incubated with THP-1 and RAW 264.7 cells, and despite the high cell viability and absence of cytotoxic effect, the treatment resulted in the expressive production of reactive oxygen species. In general, pectins from ripe and unripe guava and modified pectin from unripe guava stimulated the production of diverse cytokines, especially inflammatory cytokines, such as IL-1ß, IL 12, CCL5, CXCL10, and CXCL9, for THP-1, while IL-10 (anti-inflammatory), TNF-α and MCP-1 were stimulated in RAW 264.7 cells, demonstrating their immunomodulatory potential. Modified pectin derived from ripe guava did not promote any significant induction of the cytokines investigated. These results suggest that pectins obtained from guavas have immunomodulatory potential and deserve a more in-depth investigation using other cellular models and/or use of higher concentrations and in vivo models tests so their immunomodulatory benefits can be prove

Pectins/analysis , Immunomodulation/drug effects , Fruit/adverse effects , Polysaccharides , Therapeutics , Macrophages/classification
Braz. oral res. (Online) ; 34: e031, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089386


Abstract: Probiotic therapy is a viable alternative to chlorhexidine, a widely used antiseptic in dentistry that produces significant adverse effects. This systematic review aimed to analyze the effects of probiotics on experimental gingivitis in humans. Two independent reviewers conducted a comprehensive literature search until March 2019. Randomized clinical trials and controlled clinical trials were selected. Outcome data were extracted and critically analyzed. A total of five articles were included in the qualitative synthesis. No meta-analysis could be conducted due to the heterogeneity of the selected studies. The use of probiotics showed a slight improvement in clinical parameters. Changes in gingival crevicular fluid volume were lower in the presence of the probiotic than in the placebo group. All the studies showed that the immediate, positive effects of probiotics during the period of discontinued mechanical oral hygiene were due to the modulation of the host response, not the anti-plaque effect. Investigators should conduct randomized clinical trials to elucidate the mechanisms of probiotic action and develop improved delivery systems.

Humans , Male , Female , Probiotics/therapeutic use , Immunomodulation , Gingivitis/prevention & control , Placebos , Gingival Crevicular Fluid , Microbiota , Gingivitis/physiopathology
Rev. chil. infectol ; 36(3): 341-352, jun. 2019. graf
Article in Spanish | LILACS | ID: biblio-1013792


Resumen La malaria asociada al embarazo es un evento poco estudiado en América Latina. Los abundantes trabajos sobre el problema en África llevan a pensar que esta infección genera una modulación de la respuesta inmune y alteraciones en el ambiente placentario, eventos cruciales para el adecuado desarrollo del feto y el neonato. La inmunidad contra Plasmodium spp es compleja porque involucra diversos factores que amplían las posibilidades de desenlaces, los que finalmente conducen a los diferentes fenotipos clínicos de la enfermedad. Uno de los desenlaces inmunológicos en infecciones por Plasmodium spp es la modulación de la respuesta inmune hacía un perfil regulador. Esta regulación inducida por la infección malárica resulta ventajosa para la persistencia del parásito en el hospedero, y adicionalmente, podría generar eventos adversos en la respuesta inmune general de los individuos infectados. El objetivo de esta revisión es abordar los mecanismos con los cuales Plasmodium spp modula la respuesta inmune del hospedero y exponer las consecuencias de las infecciones maláricas en el contexto madre-neonato.

Pregnancy-associated malaria is an understudied event in Latin America. Most works about malaria in pregnancy have been conducted in Africa. These studies indicate that the infection generates immune response modulation and alterations in the placental environment, key factors for the proper development of the fetus and neonate. Immunity against Plasmodium spp is complex since involves several factors that increase the possible infection outcomes. One of these immunological outcomes is the immune response modulation towards a regulatory profile, which is advantageous for the persistence of the parasite in the host; additionally, it could generate adverse events in the general immune response of infected individuals. The objective of this review is to address the Plasmodium spp mechanisms of modulation in the host immune response and expose the consequences of malarial infections in the mother-neonate context.

Humans , Female , Pregnancy , Infant, Newborn , Plasmodium/immunology , Pregnancy Complications, Parasitic/immunology , Immunomodulation/physiology , Malaria/immunology , Placenta/immunology , Placenta/parasitology , Plasmodium/physiology , Host-Parasite Interactions/immunology , Immune System/immunology
Article in English | WPRIM | ID: wpr-766316


Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.

Angiogenesis Modulating Agents , Cooperative Behavior , Denosumab , Dental Hygienists , Dentists , Diphosphonates , Humans , Immunomodulation , Immunotherapy , Jaw , Oral and Maxillofacial Surgeons , Oral Manifestations , Osteonecrosis , Pathology
Article in English | WPRIM | ID: wpr-719482


The field of biomaterials has seen a strong rejuvenation due to the new potential to modulate immune system in our body. This special class of materials is called “immunomodulatory biomaterials”. Generally, three fundamental strategies are followed in the design of immunomodulatory biomaterials: (1) immuno-inert biomaterials, (2) immuno-activating biomaterials, and (3) immuno-tolerant biomaterials. While many applications of immuno-inert biomaterials such as biocompatible medical implants have been already proposed in the past decades, the ability to engineer biological activity into synthetic materials greatly increases the number of their potential uses and improves their performance in more traditional applications. The major focus of researchers is now set on developing immuno-tolerant biomaterials for anti-inflammatory therapies. In this review, we therefore introduce recent developments of immuno-tolerant biomaterials. Especially we introduce an apoptotic cell membrane-inspired polymer and its post-inflammatory effects on immune cells in this article.

Anti-Inflammatory Agents , Apoptosis , Biocompatible Materials , Immune System , Immunomodulation , Phosphatidylserines , Polymers , Rejuvenation
Article in English | WPRIM | ID: wpr-719411


Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.

Animals , Dinoprostone , Homeostasis , Humans , Immunomodulation , In Vitro Techniques , Mesenchymal Stem Cells , Mesoderm , Multipotent Stem Cells , Regeneration , Regenerative Medicine , T-Lymphocytes , Toll-Like Receptors
Korean Circulation Journal ; : 314-325, 2019.
Article in English | WPRIM | ID: wpr-738791


Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Adoptive transfer of multiple stem cell types into failing human hearts has demonstrated safety however the beneficial effects in patients with cardiovascular disorders have been modest. Modest improvement in patients with cardiac complications warrants identification of a novel stem cell population that possesses effective reparative properties and improves cardiac function after injury. Recently we have shown in a mouse model and a porcine pre-clinical animal model, that cortical bone derived stem cells (CBSCs) enhance cardiac function after MI and/or ischemia-reperfusion injury. These beneficial effects of allogeneic cell delivery appear to be mediated by paracrine mechanisms rather than by transdifferentiation of injected cells into vessels and/or immature myocytes. This review will discuss role of CBSCs in cardiac wound healing. After having modest beneficial improvement in most of the clinical trials, a critical need is to understand the interaction of the transplanted stem cells with the ischemic cardiac environment. Transplanted stem cells are exposed to pro-inflammatory factors and activated immune cells and fibroblasts, but their interactions remain unknown. We have shown that CBSCs modulate different processes including modulation of the immune response, angiogenesis, and restriction of infarct sizes after cardiac injury. This review will provide information on unique protective signature of CBSCs in rodent/swine animal models for heart repair that should provide basis for developing novel therapies for treating heart failure patients.

Adoptive Transfer , Animals , Cell- and Tissue-Based Therapy , Fibroblasts , Fibrosis , Heart , Heart Failure , Humans , Immunomodulation , Mice , Models, Animal , Mortality , Muscle Cells , Myocardial Infarction , Myocardial Ischemia , Reperfusion Injury , Stem Cells , Wound Healing , Wounds and Injuries
J. venom. anim. toxins incl. trop. dis ; 25: e20190008, 2019. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1020026


Visceral leishmaniasis is a complex neglected tropical disease caused by Leishmania donovani complex. Its current treatment reveals strong limitations, especially high toxicity. In this context, natural products are important sources of new drug alternatives for VL therapy. Therefore, the antileishmanial and immunomodulatory activity of compounds isolated from Nectandra oppositifolia (Lauraceae) was investigated herein. Methods: The n-hexane extract from twigs of N. oppositifolia were subjected to HPLC/HRESIMS and bioactivity-guided fractionation to afford compounds 1 and 2 which were evaluated in vitro against Leishmania (L.) infantum chagasi and NCTC cells. Results: The n-hexane extract displayed activity against L. (L.) infantum chagasi and afforded isolinderanolide E (1) and secosubamolide A (2), which were effective against L. (L.) infantum chagasi promastigotes, with IC50 values of 57.9 and 24.9 µM, respectively. Compound 2 was effective against amastigotes (IC50 = 10.5 µM) and displayed moderate mammalian cytotoxicity (CC50 = 42 µM). The immunomodulatory studies of compound 2 suggested an anti-inflammatory activity, with suppression of IL-6, IL-10, TNF with lack of nitric oxide. Conclusion: This study showed the antileishmanial activity of compounds 1 and 2 isolated from N. oppositifolia. Furthermore, compound 2 demonstrated an antileishmanial activity towards amastigotes associated to an immunomodulatory effect.(AU)

Biological Products , Lauraceae , Immunomodulation , Leishmaniasis, Visceral , Leishmania donovani , In Vitro Techniques
Article in English | WPRIM | ID: wpr-785903


Macrophages play essential roles in innate immune responses by producing various immune mediators. Therefore, modulating macrophage function is an attractive strategy to treat immune disorders. Aralia cordata var. continentalis (AC), known as “Dokwhal” in Korea, possesses various biological and medicinal functions, including immunomodulation. The present study investigated the effect of the hot water extract of AC (HAC) on RAW264.7 murine macrophages. When these cells were treated with HAC, nitric oxide production and inducible nitric oxide synthase expression was induced dose-dependently. In addition, HAC treatment triggered the secretion of innate immune cytokines, such as TNF-α and IL-6. Phagocytosis, measured by FITC-dextran internalization showed that HAC stimulated the phagocytic activity of macrophages. Furthermore, HAC promoted the production of reactive oxygen species in RAW264.7 cells, determined by CM-H2DCFDA. In addition, the immunoblot analysis of intracellular signaling proteins revealed that NF-kB and MAPK signaling pathways, which are important signaling mediators of inflammation, are upregulated by HAC. In conclusion, these findings suggested that HAC can stimulate macrophage activity, and NF-kB and MAPK signaling pathways might be involved in the immunostimulatory effects of HAC.

Aralia , Cytokines , Immune System Diseases , Immunity, Innate , Immunomodulation , Inflammation Mediators , Interleukin-6 , Intracellular Signaling Peptides and Proteins , Korea , Macrophages , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase Type II , Phagocytosis , Reactive Oxygen Species , Water