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1.
Life Sci ; 232: 116632, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278944

RESUMO

AIMS: The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. MAIN METHODS: Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. KEY FINDINGS: miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. SIGNIFICANCE: We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.


Assuntos
Células-Tronco Mesenquimais/metabolismo , MicroRNAs/sangue , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Exossomos , Humanos , Inflamação/terapia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo
2.
Autoimmun Rev ; 18(8): 751-760, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181324

RESUMO

Neutrophils derive from hematopoietic stem cells (HSCs) with systemic inflammation driving their activation and differentiation to myeloid progenitors to ensure enhanced myelopoiesis. Epigenetic reprograming and re-education of these HSCs produces neutrophils primed towards elimination of pathogens and increased inflammatory response. Neutrophils -an important component of acute inflammation- are not present in chronic inflammatory tissues leading to the false assumption that they may not be as important for the latter. Activated neutrophils may release Neutrophil Extracellular Traps (NETs) during a distinct form of cell death, named NETosis; NETs are rich in bioactive molecules that promote thrombosis (including atherothrombosis), inflammation and fibrosis. Thus, although neutrophils may not be present in chronic inflammatory lesions, their remnants may amplify the inflammatory response beyond their short life-span in the tissues. Herein, we review current evidence supporting a role of neutrophils and NETosis in tissue injury and dysfunction in systemic autoimmunity using as disease paradigms Systemic Lupus Erythematosus (SLE) and the ANCA-associated vasculitides (AAV). We also discuss the mechanisms involved and their potential as targets for novel therapy and drug repositioning.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Neutrófilos/imunologia , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Morte Celular , Diferenciação Celular , Armadilhas Extracelulares/imunologia , Fibrose , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Mielopoese , Neutrófilos/patologia
3.
Biochim Biophys Acta Rev Cancer ; 1872(1): 89-102, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31202687

RESUMO

Metastasis is a complex systemic disease that develops as a result of interactions between tumor cells and their local and distant microenvironments. Local and systemic immune-related changes play especially critical roles in limiting or enabling the development of metastatic disease. Although anti-tumor immune responses likely eliminate most early primary and metastatic lesions, factors secreted by cancer or stromal cells in the primary tumor can mobilize and activate cells in distant organs in a way that promotes the outgrowth of disseminated cancer cells into macrometastatic lesions. Therefore, the prevention, detection, and effective treatment of metastatic disease require a deeper understanding of the systemic effects of primary tumors as well as predisposing hereditary and acquired host factors including chronic inflammatory conditions. The success of immunotherapy in a subset of cancer patients is an example of how modulating the microenvironment and tumor-immune cell interactions can be exploited for the effective eradiation of even advanced-stage tumors. Here, we highlight emerging insights and clinical implications of cancer as a systemic disease.


Assuntos
Imunoterapia , Inflamação/genética , Metástase Neoplásica/genética , Neoplasias/genética , Comunicação Celular/genética , Comunicação Celular/imunologia , Humanos , Imunidade Inata/genética , Inflamação/imunologia , Inflamação/terapia , Metástase Neoplásica/imunologia , Metástase Neoplásica/terapia , Neoplasias/imunologia , Neoplasias/terapia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
4.
J Dairy Sci ; 102(8): 6718-6725, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31155246

RESUMO

This study aimed to screen lactic acid bacteria (LAB) for their anti-inflammatory activity by using RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis. In all, 192 LAB strains were isolated from healthy human feces, of which 8 strains showed excellent nitric oxide (NO) inhibitory activity. Peptidoglycan extracts of these 8 LAB strains were subjected to NO assay, Western blot, and ELISA. Among the 8 tested strains, extracts of 4 strains significantly inhibited the production of NO, related enzyme activities such as inducible nitric oxide synthase and cyclooxygenase 2, and key cytokines such as tumor necrosis factor-α and IL-6 in RAW264.7 cells. The 4 strains belonged to Lactobacillus (CAU1054, CAU1055, CAU1064, and CAU1301). Oral administration of the 4 strains inhibited DSS-induced body weight loss, colon shortening, and colon damage in ICR mice. The colon tissue of the mice treated with Lactobacillus plantarum strain CAU1055 had significantly reduced levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor-α, and IL-6. We found that strain CAU1055 could be used as a candidate probiotic strain for the prevention and treatment of inflammatory bowel disease. Further studies are warranted to confirm the mechanisms of interaction between peptidoglycan of L. plantarum strain CAU1055 and upstream cellular signaling mediators.


Assuntos
Colite/prevenção & controle , Sulfato de Dextrana/farmacologia , Inflamação/prevenção & controle , Lactobacillus plantarum/fisiologia , Lipopolissacarídeos/farmacologia , Animais , Colite/induzido quimicamente , Colite/terapia , Inibidores de Ciclo-Oxigenase 2 , Citocinas/antagonistas & inibidores , Modelos Animais de Doenças , Fezes/microbiologia , Humanos , Inflamação/terapia , Lactobacillus plantarum/isolamento & purificação , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Probióticos/administração & dosagem , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
5.
Gastroenterology ; 157(3): 624-636, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31220424

RESUMO

As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in the development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of fecal microbiota transplantation. We discuss opportunities for treatment of other diseases with fecal microbiota transplantation, based on findings from small clinical and preclinical studies.


Assuntos
Doenças do Sistema Nervoso Central/terapia , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Gastroenteropatias/terapia , Microbioma Gastrointestinal , Inflamação/terapia , Animais , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/microbiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/microbiologia , Humanos , Inflamação/diagnóstico , Inflamação/microbiologia , Recidiva , Resultado do Tratamento
7.
Mar Drugs ; 17(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072006

RESUMO

Lipids used in intravenous nutrition support (i.e., parenteral nutrition) provide energy, building blocks, and essential fatty acids. These lipids are included as emulsions since they need to be soluble in an aqueous environment. Fish oil is a source of bioactive omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid). Lipid emulsions, including fish oil, have been used for parenteral nutrition for adult patients post-surgery (mainly gastrointestinal). This has been associated with alterations in biomarkers of inflammation and immune defense, and in some studies, a reduction in length of intensive care unit and hospital stay. These benefits, along with a reduction in infections, are emphasized through recent meta-analyses. Perioperative administration of fish oil may be superior to postoperative administration, but this requires further exploration. Parenteral fish oil has been used in critically ill adult patients. Here, the influence on inflammatory processes, immune function, and clinical endpoints is less clear. However, some studies found reduced inflammation, improved gas exchange, and shorter length of hospital stay in critically ill patients if they received fish oil. Meta-analyses do not present a consistent picture but are limited by the small number and size of studies. More and better trials are needed in patient groups in which parenteral nutrition is used and where fish oil, as a source of bioactive omega-3 fatty acids, may offer benefits.


Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/uso terapêutico , Nutrição Parenteral/métodos , Adulto , Estado Terminal/terapia , Procedimentos Cirúrgicos do Sistema Digestório , Ácidos Docosa-Hexaenoicos/biossíntese , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/biossíntese , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/biossíntese , Humanos , Inflamação/terapia , Assistência Perioperatória , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Curr Top Microbiol Immunol ; 421: 319-359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123895

RESUMO

The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in etiopathogenesis and ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer (GC) cases. As we increase our understanding of how chronic inflammation develops in the stomach and contributes to carcinogenesis, there is increasing interest in targeting cancer-promoting inflammation as a strategy to treat GC. Moreover, once cancer develops and anti-cancer immune responses are suppressed, there is evidence of a substantial shift in the microenvironment and new targets for immune therapy emerge. In this chapter, we provide insight into inflammation-related factors, including T lymphocytes, macrophages, pro-inflammatory chemokines, and cytokines, which promote H. pylori-associated GC initiation and growth. While intervening with chronic inflammation is not a new practice in rheumatology or gastroenterology, this approach has not been fully explored for its potential to prevent carcinogenesis or to contribute to the treatment of GC. This review highlights current and possible strategies for therapeutic intervention including (i) targeting pro-inflammatory mediators, (ii) targeting growth factors and pathways involved in angiogenesis in the gastric tumor microenvironment, and (iii) enhancing anti-tumor immunity. In addition, we highlight a significant number of clinical trials and discuss the importance of individual tumor characterization toward offering personalized immune-related therapy.


Assuntos
Inflamação/imunologia , Inflamação/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Citocinas/imunologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/terapia , Helicobacter pylori/patogenicidade , Humanos , Inflamação/microbiologia , Inflamação/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia , Microambiente Tumoral
9.
Life Sci ; 231: 116483, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102743

RESUMO

Alzheimer's disease (AD) remains one of the greatest global concerns. Current treatment of AD - the acetylcholinesterase inhibitors - provides temporary improvement of cognitive functions, but does not affect the core of the underlying pathological process. There is still the need for alternative approaches, preferably ones based on the upstream events in the AD pathogenesis. The nature of AD pathogenesis remains complicated and not entirely explained. It is assumed to comprise of many interrelated events which can sequentially lead to further pathologies - as a kind of vicious cycle. The solution in this case could be to interact with these processes on multiple levels at the same time. The proposed approach hopes to achieve the state of equilibrium between two pathological pathways via reducing their dynamics on appropriate levels. The first step is to inhibit Tumor Necrosis Factor signaling related to inflammatory response. The second is to take advantage of the influence of insulin signaling on amyloid-ß processing to restore its proper clearance. Employing two only partially-beneficial approaches into a novel approach aims at breaking the "vicious cycle" and eliciting synergistic effect via working on different levels simultaneously. The effect of such therapy could allow physicians to completely inhibit neural damage. The proposed strategy may prove easily introducible as an efficacious clinical approach employing novel anti-TNF agents in combination with anti-diabetic agents. Data is needed on its influence on cognitive functions, any occurrence of adverse effects, and the development of models of optimal doses and their temporal location.


Assuntos
Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/terapia , Diabetes Mellitus/terapia , Inflamação/terapia , Anti-Inflamatórios/uso terapêutico , Cognição , Demência/tratamento farmacológico , Demência/fisiopatologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Sinergismo Farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/metabolismo , Insulina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 252-255, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106548

RESUMO

OBJECTIVE: To ivestigate the effect of daily walking number on clinical, inflammatory and nutritional indexes for patients with chronic kidney disease. METHODS: 90 non-dialysis patients with chronic kidney disease were selected and randomly divided equally into three groups, for groups A, B and C. 30 patients for group A were asked for the number of daily walk should less than 5 000 steps, while group B patients were asked for 5 000-9 999 steps of walk and group C for more than 10 000 steps. Basic treatments were given for each group of patients and basic information, clinical, inflammatory and nutritional datas of patients were collected. RESULTS: 87 patients with chronic kidney disease completed the study, with baseline data between group A, B, C (n=30, 29, 28) consistently. After 3 months of exercise, there were no significant changes on blood lipids, serum uric acid and parathyroid hormone (PTH) for three groups, with serum creatinine of three groups stably. However, in group C, hemoglobin, ferritin, transferrin saturation were found increased significantly (P<0.05). For nutritional indexes, increasing of albumin and prealbumin level were found in three groups, while significant differences were only found in group B and C (P<0.05) and group C increased most. There were no significant change on body mass index (BMI), upper arm skinfold thickness and SGA score in three groups. For inflammatory data, significant decrease of C-reactive protein (CRP) and interleukin-6 (IL-6) were only seen in group C (P<0.05). CONCLUSION: Walking does not increase the burden of the kidney, but can improve the nutrition and clinical indicators of patients, reduce inflammation.


Assuntos
Inflamação/terapia , Estado Nutricional , Insuficiência Renal Crônica/sangue , Caminhada , Proteína C-Reativa/análise , Humanos , Inflamação/sangue , Interleucina-6/sangue , Lipídeos/sangue , Hormônio Paratireóideo/sangue , Diálise Renal , Ácido Úrico/sangue
11.
Croat Med J ; 60(2): 127-140, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31044584

RESUMO

AIM: To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca2+), and hypoxia-inducible factor 1α (HIF1α) in neurorestoration following the application of EMF. METHODS: We reviewed the existing studies within the public domain and cross-evaluated their results in order to conclude on the molecular mechanisms of microglia-astrocyte crosstalk at work during EMF treatment. RESULTS: The existing studies suggest that EMF induces the increase of HSP70 expression and inhibition of HIF1α, thus decreasing inflammation and allowing the microglia-astrocyte crosstalk to initiate the formation of a glial scar within the central nervous system. Furthermore, by potentially up-regulating A2A and A3 adenosine receptors, EMF increases cAMP accumulation from astrocytes and reduces the expression of inflammatory cytokines TNF α and IL-8, thus initiating neurorestoration. CONCLUSION: The microglia-astrocyte crosstalk during EMF treatment is crucial for the initiation of neurorestoration. Elucidating the exact mechanisms of EMF actions upon microglia and astrocytes, and its role in neurorestoration could be a key step in further research of the therapeutic potential of EMFs in various neurological disorders.


Assuntos
Astrócitos/fisiologia , Terapia de Campo Magnético , Microglia/fisiologia , Doenças Neurodegenerativas/terapia , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Células Cultivadas , Citocinas , Campos Eletromagnéticos , Proteínas de Choque Térmico/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , Inflamação/terapia , Doenças Neurodegenerativas/imunologia , Receptor Cross-Talk , Fator de Necrose Tumoral alfa
13.
Khirurgiia (Mosk) ; (4): 42-51, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31120446

RESUMO

AIM: To present treatment strategy for large volumes of injectable non-absorbable 'shell-less' soft tissue fillers (vaseline, synthol, silicone etc.). MATERIAL AND METHODS: The authors present an experience of surgical treatment of 8 patients who underwent injections of medical vaseline (breast augmentation, n=5) and synthol (muscles enlargement, n=3) and review of the current literature devoted to this problem. RESULTS: Injection of large amounts (over 50 ml) of non-absorbable fillers into soft tissues is unacceptable and leads to numerous complications. Oil-based 'shell-less' fillers cannot be removed by minimally invasive techniques (puncture, mini-incisions, etc.) due to multiple diffuse lesions in the form of oleogranulomas (cysts of different size) and surrounding widespread inflammation and fibrosis of tissues. Surgery is the only adequate method. However, this approach is followed by scars and often tissue contour deformation. Migration of these fillers to other anatomical areas (from the neck to the lower extremities) significantly complicates the situation, treatment and results. In case of categorical refusal of patients from surgical treatment and no complaints, they should be properly informed about possible consequences and complications and dynamic medical supervision is necessary. Intraoperative ultrasound examination is useful for the control of radical removal of pathological areas. Timely removal of non-absorbable fillers allows to avoid serious complications and to achieve good aesthetic results.


Assuntos
Técnicas Cosméticas/efeitos adversos , Fibrose/terapia , Inflamação/terapia , Óleos/efeitos adversos , Vaselina/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Preenchedores Dérmicos/efeitos adversos , Fibrose/diagnóstico , Fibrose/etiologia , Fibrose/cirurgia , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Inflamação/cirurgia , Injeções , Óleos/administração & dosagem , Vaselina/administração & dosagem
15.
Immunity ; 50(4): 796-811, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995500

RESUMO

The ß common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmune disease, and others show promising early clinical activity. These approaches are based on our understanding of the inflammatory roles of these cytokines; however, GM-CSF also participates in the resolution of inflammation, and IL-3 and IL-5 may also have such properties. Here, we review the functions of the ß common cytokines in health and disease. We discuss preclinical and clinical data, highlighting the potential inherent in targeting these cytokine pathways, the limitations, and the important gaps in understanding of the basic biology of this cytokine family.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Inflamação/imunologia , Interleucina-3/imunologia , Interleucina-5/imunologia , Animais , Doenças Autoimunes/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/deficiência , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Hematopoese/imunologia , Humanos , Inflamação/terapia , Interleucina-3/antagonistas & inibidores , Interleucina-3/deficiência , Interleucina-3/genética , Interleucina-5/antagonistas & inibidores , Interleucina-5/deficiência , Interleucina-5/genética , Camundongos , Camundongos Knockout , Família Multigênica , Neoplasias/imunologia , Neoplasias/terapia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/imunologia , Receptores de Interleucina-3/genética , Receptores de Interleucina-3/imunologia , Receptores de Interleucina-5/genética , Receptores de Interleucina-5/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Transdução de Sinais , Relação Estrutura-Atividade , Vacinação , Cicatrização/imunologia
16.
Immunity ; 50(4): 871-891, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995504

RESUMO

Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, and cancer. Manipulating cytokine pathways, therefore, is one of the most effective strategies to treat various diseases. IL-10 family cytokines exert essential functions to maintain tissue homeostasis during infection and inflammation through restriction of excessive inflammatory responses, upregulation of innate immunity, and promotion of tissue repairing mechanisms. Their important functions in diseases are supported by data from many preclinical models, human genetic studies, and clinical interventions. Despite significant efforts, however, there is still no clinically approved therapy through manipulating IL-10 family cytokines. Here, we summarize the recent progress in understanding the biology of this family of cytokines, suggesting more specific strategies to maneuver these cytokines for the effective treatment of inflammatory diseases and cancers.


Assuntos
Imunidade Inata , Interleucina-10/imunologia , Interleucinas/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Citocinas/classificação , Citocinas/genética , Regulação da Expressão Gênica , Humanos , Infecção/imunologia , Infecção/terapia , Inflamação/imunologia , Inflamação/terapia , Interleucina-10/genética , Interleucinas/genética , Subpopulações de Linfócitos/imunologia , Camundongos , Família Multigênica , Células Mieloides/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Transdução de Sinais , Fatores de Transcrição/fisiologia
17.
J Immunol Res ; 2019: 3876896, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001563

RESUMO

Hepatic inflammation and injury may result from the translocation of pathological bacteria and their proinflammatory mediators. Probiotics attenuate hepatic diseases related to inflammation by exhibiting immunoregulatory effects. Therefore, this study was conducted to evaluate lipid reduction and immunoregulatory potentials of probiotic bacteria in vitro. HepG2 cells treated with total cellular fluid (TCF) of LABs reduced lipid accumulation. Moreover, cells responded to lipopolysaccharide (LPS) by producing higher levels of IL-6, IL-8, MCP-1, and TNF-α. TCF of LABs treatment showed remarkably diminished levels of the expression of these cytokines via modulation of the expression of TLR-negative regulators, as well as MAPK and NF-κB pathways. Moreover, heat-killed LABs were able to diminish TGF-ß, IL-1ß, and IL-6 and to increase IL-10 and TLR4 levels in THP-1 cells. LABs also decreased the protein level of TNF-α. These results demonstrated that immunobiotics exhibit potent immunoregulatory activity and may be used as effective therapeutic agents to alleviate inflammatory response.


Assuntos
Fígado Gorduroso/terapia , Lactobacillales , Probióticos/farmacologia , Transdução de Sinais , Receptor 4 Toll-Like/imunologia , Citocinas/imunologia , Fígado Gorduroso/imunologia , Alimentos Fermentados/microbiologia , Células Hep G2 , Humanos , Inflamação/imunologia , Inflamação/terapia , Lipopolissacarídeos , Células THP-1
18.
Parasitol Int ; 71: 121-125, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30980897

RESUMO

The cestode Hymenolepis diminuta is highly prevalent in wild rat populations and has also been observed rarely in humans, generally causing no apparent harm. The organism has been studied for decades in the laboratory, and its colonization of laboratory rats has recently been shown as protective against some inflammation-associated disorders. Recently, H. diminuta has become a leading candidate for helminth therapy, an emerging method of "biota enrichment" used to treat or prevent inflammatory diseases of humans in Western society. While most of the experimental isolates of H. diminuta are identified based on typical morphological features, hymenolepidid tapeworms may represent complexes of cryptic species as detected by molecular sequence data. In the present study, we explored the diversity of laboratory-kept strains using partial sequences of two genes (lsrDNA and cox1) and determined that H. diminuta isolates currently considered for therapeutic purposes in the US and Europe belong to a single, genetically nearly uniform lineage, showing only little genetic deviation from wild-caught isolates.


Assuntos
Animais de Laboratório/parasitologia , Cestoides/genética , Variação Genética , Inflamação/terapia , Animais , Cestoides/fisiologia , Infecções por Cestoides , Complexo IV da Cadeia de Transporte de Elétrons/genética , Filogenia , Ratos/parasitologia , Subunidades Ribossômicas Maiores de Eucariotos/genética , Análise de Sequência de DNA
19.
Nutrients ; 11(3)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897686

RESUMO

The gut microbiota is increasingly recognized as an important modulator of human health. As such, there is a growing need to identify effective means of selectively modifying gut microbial communities. Bacteriophages, which were briefly utilized as clinical antimicrobials in the early 20th century, present an opportunity to selectively reduce populations of undesirable microorganisms. However, whether intentional consumption of specific bacteriophages affects overall gut ecology is not yet known. Using a commercial cocktail of Escherichia coli-targeting bacteriophages, we examined their effects on gut microbiota and markers of intestinal and systemic inflammation in a healthy human population. In a double-blinded, placebo-controlled crossover trial, normal to overweight adults consumed bacteriophages for 28 days. Stool and blood samples were collected and used to examine inflammatory markers, lipid metabolism, and gut microbiota. Reductions in fecal E. coli loads were observed with phage consumption. However, there were no significant changes to alpha and beta diversity parameters, suggesting that consumed phages did not globally disrupt the microbiota. However, specific populations were altered in response to treatment, including increases in members of the butyrate-producing genera Eubacterium and a decreased proportion of taxa most closely related to Clostridium perfringens. Short-chain fatty acid production, inflammatory markers, and lipid metabolism were largely unaltered, but there was a small but significant decrease in circulating interleukin-4 (Il-4). Together, these data demonstrate the potential of bacteriophages to selectively reduce target organisms without global disruption of the gut community.


Assuntos
Colífagos , Gastroenteropatias/microbiologia , Inflamação/microbiologia , Inflamação/terapia , Adolescente , Adulto , Idoso , Suplementos Nutricionais , Método Duplo-Cego , Escherichia coli/virologia , Feminino , Microbioma Gastrointestinal , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
J Cancer Res Ther ; 15(1): 185-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880777

RESUMO

Aims: Vitamin C plays a role in chemoprevention in cancer treatment, and Vitamin C modulates many regulators of inflammation in in vitro studies. The aim of this study is to assess the effect of Vitamin C supplementation with neoadjuvant chemoradiation in esophageal adenocarcinoma on the nuclear factor-kappa B (NF-κB) and associated cytokines. Materials and Methods: A total of 20 patients undergoing multimodal treatment for esophageal adenocarcinoma were randomized to receive Vitamin C (1000 mg/day) orally for 4 weeks or no supplementation. Pre- and post-Vitamin C endoscopic biopsies were used for the study of NF-κB activity and cytokine analysis. Results: NF-κB activity along with cytokines was activated in the cancer tissue pretreatment. Down-regulation in NF-κB activity was observed in 25% of cases, two from the Vitamin C arm posttreatment. There was a significant reduction in cytokines levels in the cancer group, and this effect was more pronounced in the Vitamin C group (P < 0.05). Conclusions: Vitamin C supplementation had a mild protective effect in modulating of regulators of inflammation and carcinogenesis. Further studies with larger numbers of endpoints are needed to evaluate its effect on modulation of chemoradiation responses.


Assuntos
Adenocarcinoma/terapia , Ácido Ascórbico/administração & dosagem , Carcinogênese/efeitos dos fármacos , Suplementos Nutricionais , Neoplasias Esofágicas/terapia , Inflamação/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Idoso , Biópsia , Carcinogênese/patologia , Carcinogênese/efeitos da radiação , Quimiorradioterapia/métodos , Citocinas/metabolismo , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Mucosa Esofágica/efeitos da radiação , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Esofagectomia , Esofagoscopia , Feminino , Humanos , Inflamação/diagnóstico por imagem , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Terapia Neoadjuvante/métodos , Projetos Piloto , Resultado do Tratamento
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