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1.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371873

RESUMO

Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1ß, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.


Assuntos
Anti-Inflamatórios/uso terapêutico , Flavonoides/uso terapêutico , Terapia de Reposição Hormonal , Sistema Imunitário/efeitos dos fármacos , Imunossenescência/efeitos dos fármacos , Menopausa/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Fatores Etários , Animais , Anti-Inflamatórios/efeitos adversos , Citocinas/metabolismo , Feminino , Flavonoides/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Mediadores da Inflamação/metabolismo , Menopausa/imunologia , Menopausa/metabolismo , Fitoestrógenos/efeitos adversos , Fatores Sexuais
2.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371920

RESUMO

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.


Assuntos
Antivirais/uso terapêutico , Suplementos Nutricionais , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/virologia , Fatores Imunológicos/efeitos adversos , Resultado do Tratamento , Viroses/imunologia , Viroses/metabolismo , Viroses/virologia , Vírus/imunologia , Vírus/patogenicidade
3.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203268

RESUMO

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.


Assuntos
Antivirais/química , Portadores de Fármacos/química , Nanomedicina , Infecções Respiratórias/patologia , Vacinas Virais/química , Viroses/patologia , Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Humanos , Sistema Imunitário/metabolismo , Infecções Respiratórias/terapia , Infecções Respiratórias/virologia , SARS-CoV-2/isolamento & purificação , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Viroses/imunologia , Viroses/prevenção & controle , Viroses/terapia
4.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204326

RESUMO

Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets.


Assuntos
Imunomodulação , Neoplasias/imunologia , Neoplasias/metabolismo , Esfingolipídeos/metabolismo , Animais , Antígenos de Neoplasias/imunologia , Comunicação Celular , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Lisofosfolipídeos/metabolismo , Neoplasias/terapia , Transdução de Sinais , Esfingolipídeos/química , Esfingolipídeos/imunologia , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Resultado do Tratamento
5.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199142

RESUMO

Metabolism is the central engine of living organisms as it provides energy and building blocks for many essential components of each cell, which are required for specific functions in different tissues. Mitochondria are the main site for energy production in living organisms and they also provide intermediate metabolites required for the synthesis of other biologically relevant molecules. Such cellular processes are finely tuned at different levels, including allosteric regulation, posttranslational modifications, and transcription of genes encoding key proteins in metabolic pathways. Peroxisome proliferator activated receptor γ coactivator 1 (PGC1) proteins are transcriptional coactivators involved in the regulation of many cellular processes, mostly ascribable to metabolic pathways. Here, we will discuss some aspects of the cellular processes regulated by PGC1s, bringing up some examples of their role in mitochondrial and cellular metabolism, and how metabolic regulation in mitochondria by members of the PGC1 family affects the immune system. We will analyze how PGC1 proteins are regulated at the transcriptional and posttranslational level and will also examine other regulators of mitochondrial metabolism and the related cellular functions, considering approaches to identify novel mitochondrial regulators and their role in physiology and disease. Finally, we will analyze possible therapeutical perspectives currently under assessment that are applicable to different disease states.


Assuntos
Metabolismo Energético , Mitocôndrias/genética , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunomodulação , Redes e Vias Metabólicas , Especificidade de Órgãos , Termogênese
6.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202925

RESUMO

Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.


Assuntos
Imunomodulação , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Acetilcolina/metabolismo , Animais , Cálcio/metabolismo , Sinalização do Cálcio , Regulação da Expressão Gênica , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade , Linfócitos/imunologia , Linfócitos/metabolismo , Especificidade de Órgãos , Peptídeos/metabolismo , Peptídeos/farmacologia , Receptores Muscarínicos/genética , Receptores Nicotínicos/genética , Transdução de Sinais
7.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206399

RESUMO

Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy.


Assuntos
Suscetibilidade a Doenças , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Biomarcadores , Comunicação Celular , Gerenciamento Clínico , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/terapia , Ligantes , Ligação Proteica , Receptores de Células Matadoras Naturais/genética , Receptores de Células Matadoras Naturais/metabolismo , Resultado do Tratamento , Evasão Tumoral/genética , Evasão Tumoral/imunologia
8.
Adv Exp Med Biol ; 1315: 99-128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302690

RESUMO

Hydrogen sulfide (H2S) is the "third gasotransmitter" recognized alongside nitric oxide (NO) and carbon monoxide (CO). H2S exhibits an array of biological effects in mammalian cells as revealed by studies showing important roles in the cardiovascular system, in cell signalling processes, post-translational modifications and in the immune system. Regarding the latter, using pharmacological and genetic approaches scientists have shown this molecule to have both pro- and anti-inflammatory effects in mammalian systems. The anti-inflammatory effects of H2S appeared to be due to its inhibitory action on the nuclear factor kappa beta signalling pathway; NF-kB representing a transcription factor involved in the regulation pro-inflammatory mediators like nitric oxide, prostaglandins, and cytokines. In contrast, results from several animal model describe a more complicated picture and report on pro-inflammatory effects linked to exposure to this molecule; linked to dosage used and point of administration of this molecule. Overall, roles for H2S in several inflammatory diseases spanning arthritis, atherosclerosis, sepsis, and asthma have been described by researchers. In light this work fascinating research, this chapter will cover H2S biology and its many roles in the immune system.


Assuntos
Gasotransmissores , Sulfeto de Hidrogênio , Animais , Sistema Imunitário/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais
9.
Hematology ; 26(1): 478-490, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34238135

RESUMO

OBJECTION: Primary myelofibrosis (PMF) is a familiar chronic myeloproliferative disease with an unfavorable prognosis. The effect of infection on the prognosis of patients with PMF is crucial. Immune system dysregulation plays a central role in the pathophysiology of PMF. To date, very little research has been conducted on the molecular mechanism of immune compromise in patients with PMF. METHODS: To explore potential candidate genes, microarray datasets GSE61629 and 26049 were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PMF patients and normal individuals were evaluated, gene function was measured and a series of hub genes were identified. Several significant immune cells were selected via cell type enrichment analysis. The correlation between hub genes and significant immune cells was determined. RESULTS: A total of 282 DEGs were found, involving 217 upregulated genes and 65 downregulated genes. Several immune cells were found to be reduced in PMF, such as CD4+ T cells, CD4+ Tems, CD4+ memory T cells. Gene Ontology (GO) enrichment analysis of DEGs reflected that most biological processes were associated with immune processes. Six hub genes, namely, HP, MPO, MMP9, EPB42, SLC4A1, and ALAS2, were identified, and correlation analysis revealed that these hub genes have a negative correlation with immune cell abundance. CONCLUSIONS: Taken together, the gene expression profile of whole blood cells in PMF patients indicated a battery of immune events, and the DEGs and hub genes might contribute to immune system dysregulation.


Assuntos
Mielofibrose Primária/genética , Transcriptoma , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade , Imunidade Celular , Mielofibrose Primária/imunologia
10.
Commun Biol ; 4(1): 670, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083737

RESUMO

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.


Assuntos
Afro-Americanos/genética , Grupo com Ancestrais do Continente Europeu/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Genômica/métodos , Neoplasias da Próstata/genética , Afro-Americanos/estatística & dados numéricos , Idoso , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/imunologia , Estudos Retrospectivos , Estados Unidos
11.
Nat Immunol ; 22(7): 914-927, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099919

RESUMO

To better define the control of immune system regulation, we generated an atlas of microRNA (miRNA) expression from 63 mouse immune cell populations and connected these signatures with assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq) and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells. miRNA complexity was relatively low, with >90% of the miRNA compartment of each population comprising <75 miRNAs; however, each cell type had a unique miRNA signature. Integration of miRNA expression with chromatin accessibility revealed putative regulatory elements for differentially expressed miRNAs, including miR-21a, miR-146a and miR-223. The integrated maps suggest that many miRNAs utilize multiple promoters to reach high abundance and identified dominant and divergent miRNA regulatory elements between lineages and during development that may be used by clustered miRNAs, such as miR-99a/let-7c/miR-125b, to achieve distinct expression. These studies, with web-accessible data, help delineate the cis-regulatory elements controlling miRNA signatures of the immune system.


Assuntos
Perfilação da Expressão Gênica , Sistema Imunitário/metabolismo , MicroRNAs/genética , Regiões Promotoras Genéticas , Transcriptoma , Animais , Células Cultivadas , Imunoprecipitação da Cromatina , Biologia Computacional , Regulação da Expressão Gênica no Desenvolvimento , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/metabolismo , RNA-Seq
12.
Pharm Biol ; 59(1): 696-703, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34110959

RESUMO

CONTEXT: COVID-19 is a novel coronavirus that causes a severe infection in the respiratory system. Nigella sativa L. (Ranunculaceae) is an annual flowering plant used traditionally as a natural food supplement and multipurpose medicinal agent. OBJECTIVE: The possible beneficial effects of N. sativa, and its constituent, thymoquinone (TQ) on COVID-19 were reviewed. METHODS: The key words including, COVID-19, N. sativa, thymoquinone, antiviral effects, anti-inflammatory and immunomodulatory effects in different databases such as Web of Science (ISI), PubMed, Scopus, and Google Scholar were searched from 1990 up to February 2021. RESULTS: The current literature review showed that N. sativa and TQ reduced the level of pro-inflammatory mediators including, IL-2, IL-4, IL-6, and IL-12, while enhancing IFN-γ. Nigella sativa and TQ increased the serum levels of IgG1 and IgG2a, and improved pulmonary function tests in restrictive respiratory disorders. DISCUSSION AND CONCLUSIONS: These preliminary data of molecular docking, animal, and clinical studies propose N. sativa and TQ might have beneficial effects on the treatment or control of COVID-19 due to antiviral, anti-inflammatory and immunomodulatory properties as well as bronchodilatory effects. The efficacy of N. sativa and TQ on infected patients with COVID-19 in randomize clinical trials will be suggested.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Benzoquinonas/farmacologia , COVID-19/tratamento farmacológico , Nigella sativa , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Antivirais/isolamento & purificação , Benzoquinonas/isolamento & purificação , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Citocinas/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/virologia , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/virologia , Nigella sativa/química , Extratos Vegetais/isolamento & purificação , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade
13.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072224

RESUMO

Rapid growth of the geriatric population has been made possible with advancements in pharmaceutical and health sciences. Hence, age-associated diseases are becoming more common. Aging encompasses deterioration of the immune system, known as immunosenescence. Dysregulation of the immune cell production, differentiation, and functioning lead to a chronic subclinical inflammatory state termed inflammaging. The hallmarks of the aging immune system are decreased naïve cells, increased memory cells, and increased serum levels of pro-inflammatory cytokines. Mesenchymal stem cell (MSC) transplantation is a promising solution to halt immunosenescence as the cells have excellent immunomodulatory functions and low immunogenicity. This review compiles the present knowledge of the causes and changes of the aging immune system and the potential of MSC transplantation as a regenerative therapy for immunosenescence.


Assuntos
Envelhecimento/imunologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunossenescência , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Rejuvenescimento , Imunidade Adaptativa , Envelhecimento/genética , Animais , Biomarcadores , Terapia Baseada em Transplante de Células e Tecidos , Regulação da Expressão Gênica , Homeostase , Humanos , Imunidade Inata , Imunossenescência/genética , Imunossenescência/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
14.
Nutrients ; 13(6)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073917

RESUMO

There has been a great deal of interest in bovine colostrum within sports nutrition over the last 25 years. Studies have investigated the effects on body composition, physical performance, recovery, gut damage and permeability, immune function, and illness risk. This narrative review considers available evidence in each of these areas. Although some studies have shown protection against performance decrements caused by periods of intensified training, there is limited evidence for effects on body composition and physical performance. There is stronger evidence for benefit on gut permeability and damage markers and on immune function and illness risk, especially during periods of intensified training. The balance of available evidence for gut permeability and illness risk is positive, but further research is required to fully determine all mechanisms responsible for these effects. Early suggestions that supplementation with bovine colostrum products could increase systemic IGF-1 levels are not supported by the balance of available evidence examining a range of doses over both short- and long-term periods. Nevertheless, dose-response studies would be valuable for determining the minimum efficacious dose, although this is complicated by variability in bioactivity between products, making any dose-response findings applicable only to the specific products used in such studies.


Assuntos
Colostro , Exercício Físico , Esportes , Animais , Atletas , Composição Corporal , Bovinos , Suplementos Nutricionais , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Sistema Imunitário/metabolismo , Fator de Crescimento Insulin-Like I/análise , Masculino , Desempenho Físico Funcional , Recuperação de Função Fisiológica , Infecções Respiratórias/epidemiologia , Fenômenos Fisiológicos da Nutrição Esportiva
15.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072535

RESUMO

In complex environments, cells have developed molecular responses to confront threats against the genome and achieve the maintenance of genomic stability assuring the transfer of undamaged DNA to their progeny. DNA damage response (DDR) mechanisms may be activated upon genotoxic or environmental agents, such as cytotoxic drugs or ultraviolet (UV) light, and during physiological processes requiring DNA transactions, to restore DNA alterations that may cause cellular malfunction and affect viability. In addition to the DDR, multicellular organisms have evolved specialized immune cells to respond and defend against infections. Both adaptive and innate immune cells are subjected to DDR processes, either as a prerequisite to the immune response, or as a result of random endogenous and exogenous insults. Aberrant DDR activities have been extensively studied in the immune cells of the innate arm, but not in adaptive immune cells. Here, we discuss how the aberrant DDR may lead to autoimmunity, with emphasis on the adaptive immune cells and the potential of therapeutic targeting.


Assuntos
Imunidade Adaptativa , Dano ao DNA , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Animais , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/terapia , Autoimunidade , Biomarcadores , Citocinas/metabolismo , Reparo do DNA , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Instabilidade Genômica , Humanos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Transdução de Sinais
16.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071962

RESUMO

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.


Assuntos
Etanol/metabolismo , Inativação Metabólica , Fígado/metabolismo , Animais , Suscetibilidade a Doenças , Hepatócitos/metabolismo , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunomodulação , Metabolismo dos Lipídeos , Fígado/imunologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Redes e Vias Metabólicas , Oxirredução , Espécies Reativas de Oxigênio , Sensibilidade e Especificidade
17.
Rev. Hosp. Ital. B. Aires (2004) ; 41(2): 86-89, jun. 2021.
Artigo em Espanhol | LILACS | ID: biblio-1254573

RESUMO

El sueño es una necesidad biológica. Regula las funciones inmunitarias. Las funciones inmunológicas dependen de los ritmos circadianos y del sueño regular. Según estudios previos a la pandemia, la corta duración del sueño o privación de sueño, en la semana cercana a la vacunación, se asocia con respuestas más bajas de anticuerpos. La privación de sueño da como resultado una función inmunológica más deficiente (es decir, actividad reducida de las células natural killer, producción de IL-2 suprimida) así como un aumento de los niveles circulantes de marcadores inflamatorios (IL-6, TNF-α [factor de necrosis tumoral] y proteína C reactiva). Los médicos deben ser conscientes de que muchas enfermedades que mencionamos en esta resumida actualización son comórbidas con alteraciones del sueño, y es importante, por ello, enseñar a los pacientes a mejorar su comportamiento con respecto al sueño y fomentar la educación sobre higiene del sueño. Destacamos que, en el interrogatorio de cualquier especialidad médica, deben incorporarse preguntas sobre el "dormir", dado que el sueño de buena calidad es fundamental en la prevención y el tratamiento de diversas enfermedades. (AU)


Sleep is a biological necessity. Regulates immune functions. Immune functions depend on circadian rhythms and regular sleep. According to studies prior to the pandemic, short duration of sleep or sleep deprivation, in the week leading up to vaccination, is associated with lower antibody responses to vaccination. Sleep deprivation results in poorer immune function (i.e., reduced natural killer cell activity, suppressed IL-2 production) as well as increased circulating levels of inflammatory markers (IL-6, factor of tumor necrosis, C-reactive protein). Clinicians should be aware that many illnesses, which we mention in this brief update, are comorbid with sleep disturbances and it is therefore important to teach patients to improve their sleep behavior and should encourage sleep hygiene education . We emphasize that in the questioning of any medical specialty, questions about "sleep" should be incorporated, given that good quality sleep is essential in the prevention and treatment of various diseases. (AU)


Assuntos
Humanos , Privação do Sono/complicações , Higiene do Sono , Sono/efeitos dos fármacos , Privação do Sono/tratamento farmacológico , Vacinação , Pandemias , COVID-19/imunologia , Sistema Imunitário/metabolismo , Melatonina/uso terapêutico
18.
Front Immunol ; 12: 581799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953705

RESUMO

Forkhead box O 3 (FOXO3) is a transcription factor involved in cell metabolism, inflammation and longevity. Here, we investigated if metformin can activate FOXO3 in human immune cells and affects the subsequent level of reactive oxygen/nitrogen species (ROS/RNS) in immune cells. AMP-activated protein kinase (AMPK) and FOXO3 activation were investigated by immunoblot or flow cytometry (FC) analysis, respectively. FOXO3 target gene expression was quantified by real-time PCR. ROS/RNS measurement using dichlorodihydrofluorescein diacetate (DCFH-DA) dye was investigated by FC. The role of the FOXO3 single nucleotide polymorphisms (SNPs) rs12212067, rs2802292 and rs12206094 on ROS/RNS production was studied using allelic discrimination PCR. Metformin induced activation of AMPK (pT172) and FOXO3 (pS413). ROS/RNS level was reduced in immune cells after metformin stimulation accompanied by induction of the FOXO3 targets mitochondrial superoxide dismutase and cytochrome c. Studies in Foxo3 deficient (Foxo3-/- ) mouse splenocytes confirmed that metformin mediates its effects via Foxo3 as it attenuates ROS/RNS in myeloid cells of wildtype (WT) but not of Foxo3-/- mice. Our results suggest that FOXO3 can be activated by metformin leading to reduced ROS/RNS level in immune cells. This may add to the beneficial clinical effects of metformin observed in large cohort studies on longevity, cardiovascular and cancer risk.


Assuntos
Proteína Forkhead Box O3/metabolismo , Sistema Imunitário/efeitos dos fármacos , Metformina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Sistema Imunitário/citologia , Sistema Imunitário/metabolismo , Camundongos Knockout , Polimorfismo de Nucleotídeo Único , Baço/citologia , Baço/efeitos dos fármacos , Baço/metabolismo
19.
Nat Rev Cardiol ; 18(9): 666-682, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33958774

RESUMO

Thrombosis is the most feared complication of cardiovascular diseases and a main cause of death worldwide, making it a major health-care challenge. Platelets and the coagulation cascade are effectively targeted by antithrombotic approaches, which carry an inherent risk of bleeding. Moreover, antithrombotics cannot completely prevent thrombotic events, implicating a therapeutic gap due to a third, not yet adequately addressed mechanism, namely inflammation. In this Review, we discuss how the synergy between inflammation and thrombosis drives thrombotic diseases. We focus on the huge potential of anti-inflammatory strategies to target cardiovascular pathologies. Findings in the past decade have uncovered a sophisticated connection between innate immunity, platelet activation and coagulation, termed immunothrombosis. Immunothrombosis is an important host defence mechanism to limit systemic spreading of pathogens through the bloodstream. However, the aberrant activation of immunothrombosis in cardiovascular diseases causes myocardial infarction, stroke and venous thromboembolism. The clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is supported by the increased risk of cardiovascular events in patients with inflammatory diseases but also during infections, including in COVID-19. Clinical trials in the past 4 years have confirmed the anti-ischaemic effects of anti-inflammatory strategies, backing the concept of a prothrombotic function of inflammation. Targeting inflammation to prevent thrombosis leaves haemostasis mainly unaffected, circumventing the risk of bleeding associated with current approaches. Considering the growing number of anti-inflammatory therapies, it is crucial to appreciate their potential in covering therapeutic gaps in cardiovascular diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/tratamento farmacológico , Trombose/prevenção & controle , Anti-Inflamatórios/efeitos adversos , COVID-19/sangue , COVID-19/imunologia , Fibrinolíticos/efeitos adversos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Inflamação/sangue , Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Medição de Risco , Fatores de Risco , Transdução de Sinais , Trombose/sangue , Trombose/imunologia
20.
Nat Commun ; 12(1): 2598, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972511

RESUMO

The intestinal immune system is an important modulator of glucose homeostasis and obesity-associated insulin resistance. Dietary factors, the intestinal microbiota and their metabolites shape intestinal immunity during obesity. The intestinal immune system in turn affects processes such as intestinal permeability, immune cell trafficking, and intestinal hormone availability, impacting systemic insulin resistance. Understanding these pathways might identify mechanisms underlying treatments for insulin resistance, such as metformin and bariatric surgery, or aid in developing new therapies and vaccination approaches. Here, we highlight evolving concepts centered on intestinal immunity, diet, and the microbiota to provide a working model of obesity-related metabolic disease.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Metabólicas/imunologia , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Animais , Linfócitos B/imunologia , Citocinas/metabolismo , Dietoterapia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Resistência à Insulina/imunologia , Doenças Metabólicas/microbiologia , Doenças Metabólicas/terapia , Obesidade/dietoterapia , Obesidade/imunologia , Obesidade/terapia , Linfócitos T/imunologia
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