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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 525-529, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879101

RESUMO

OBJECTIVES: To explore the significance of coagulation and immune function indicators in clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19). METHODS: All patients with COVID-19 diagnosed and treated in First People's Hospital of Yueyang from January to March 2020 were enrolled. The general data of patients were collected. The patients were assigned into a light group (n=20), an ordinary group (n=33), a severe group (n=23), and a critically severe group (n=7) according to the severity of the disease. Coagulation and immune function indicators of each group were compared, and the relevance of coagulation and immune function indicators was analyzed. RESULTS: The age of COVID-19 patients in Yueyang City was mainly between 45 and 65 years old. There was a significant difference in the coagulation function and immune-related indicators in each group of patients (all P<0.05). CONCLUSIONS: There are some abnormalities in coagulation and immune function in patients with COVID-19, which possess significance for clinical diagnosis and treatment of the disease.


Assuntos
Coagulação Sanguínea , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Idoso , Betacoronavirus , China , Humanos , Sistema Imunitário/fisiopatologia , Pessoa de Meia-Idade , Pandemias
4.
CNS Drugs ; 34(9): 879-896, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32780300

RESUMO

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.


Assuntos
Antirreumáticos/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus , Sistema Imunitário/efeitos dos fármacos , Esclerose Múltipla , Pandemias , Pneumonia Viral , Vacinas Virais/farmacologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Risco Ajustado
5.
Medicine (Baltimore) ; 99(34): e21952, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846865

RESUMO

BACKGROUND: Sodium cantharidinate/vitamin B6 (SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.


Assuntos
Cantaridina/análogos & derivados , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/patologia , Vitamina B 6/farmacologia , Complexo Vitamínico B/farmacologia , Cantaridina/administração & dosagem , Cantaridina/farmacologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/psicologia , China/epidemiologia , Quimioterapia Combinada/métodos , Humanos , Sistema Imunitário/efeitos dos fármacos , Injeções/métodos , Fígado/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Sobrevida , Resultado do Tratamento , Vitamina B 6/administração & dosagem , Complexo Vitamínico B/administração & dosagem
6.
BMB Rep ; 53(8): 400-412, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731913

RESUMO

The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSCExos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412].


Assuntos
Infecções por Coronavirus/terapia , Exossomos/transplante , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Sistema Imunitário/metabolismo , Imunomodulação , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia
8.
Front Immunol ; 11: 1582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793223

RESUMO

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Hiperglicemia/imunologia , Síndrome Metabólica/imunologia , Obesidade/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal , Humanos , Sistema Imunitário/metabolismo , Inflamação/imunologia , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/imunologia
10.
Int J Biol Sci ; 16(14): 2479-2489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32792851

RESUMO

The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with pneumonia accompanied by coagulopathy and lymphocytopenia during COVID-19. Increased cytokine levels, the emergence of acute phase reactants, platelet activation and immune checkpoint expression are some of the biomarkers postulated in this context. As previously observed in prolonged sepsis, T-cell exhaustion due to SARS-CoV-2 and even their reduction in numbers due to apoptosis hinder the response to the infection. In this review, we synthesized the immune changes observed during COVID-19, the role of immune molecules as severity markers for patient stratification and their associated therapeutic options.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Sepse/fisiopatologia , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Biomarcadores , Transtornos da Coagulação Sanguínea/imunologia , Citocinas/metabolismo , Humanos , Sistema Imunitário , Imunidade Inata , Interferons/metabolismo , Linfopenia/imunologia , Pandemias , Fenótipo , Ativação Plaquetária
11.
J Transl Med ; 18(1): 291, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736569

RESUMO

BACKGROUND: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. METHODS: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. RESULTS: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. CONCLUSION: Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Transcriptoma , Adulto , Anticorpos Antivirais/sangue , Betacoronavirus , Infecções por Coronavirus/imunologia , Perfilação da Expressão Gênica , Humanos , Sistema Imunitário , Internet , Pandemias , Pneumonia Viral/imunologia , RNA-Seq , Software
12.
J Transl Med ; 18(1): 297, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746922

RESUMO

BACKGROUND: The severe acute respiratory syndrome virus SARS-CoV-2, a close relative of the SARS-CoV virus, is the cause of the recent COVID-19 pandemic affecting, to date, over 14 million individuals across the globe and demonstrating relatively high rates of infection and mortality. A third virus, the H5N1, responsible for avian influenza, has caused infection with some clinical similarities to those in COVID-19 infections. Cytokines, small proteins that modulate immune responses, have been directly implicated in some of the severe responses seen in COVID-19 patients, e.g. cytokine storms. Understanding the immune processes related to COVID-19, and other similar infections, could help identify diagnostic markers and therapeutic targets. METHODS: Here we examine data of cytokine, immune cell types, and disease associations captured from biomedical literature associated with COVID-19, Coronavirus in general, SARS, and H5N1 influenza, with the objective of identifying potentially useful relationships and areas for future research. RESULTS: Cytokine and cell-type associations captured from Medical Subject Heading (MeSH) terms linked to thousands of PubMed records, has identified differing patterns of associations between the four corpuses of publications (COVID-19, Coronavirus, SARS, or H5N1 influenza). Clustering of cytokine-disease co-occurrences in the context of Coronavirus has identified compelling clusters of co-morbidities and symptoms, some of which already known to be linked to COVID-19. Finally, network analysis identified sub-networks of cytokines and immune cell types associated with different manifestations, co-morbidities and symptoms of Coronavirus, SARS, and H5N1. CONCLUSION: Systematic review of research in medicine is essential to facilitate evidence-based choices about health interventions. In a fast moving pandemic the approach taken here will identify trends and enable rapid comparison to the literature of related diseases.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Pneumopatias/imunologia , Pneumonia Viral/imunologia , Publicações , Análise por Conglomerados , Comorbidade , Síndrome da Liberação de Citocina/virologia , Citocinas/imunologia , Células-Tronco Hematopoéticas/citologia , Humanos , Sistema Imunitário , Virus da Influenza A Subtipo H5N1 , Influenza Humana/imunologia , Pandemias , PubMed , Síndrome Respiratória Aguda Grave/imunologia
13.
Crit Care Nurs Q ; 43(4): 390-399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833775

RESUMO

Coronavirus disease-2019 (COVID-19) creates severe respiratory distress and often a cascade of other systemic complications impacting several organ systems. The immune response includes a cytokine storm that creates many life-threatening problems including coagulopathies, arrhythmias, and secondary infections. This article discusses the multisystem responses to the physical insults created by this corona virus.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Sistema Cardiovascular/virologia , Trato Gastrointestinal/virologia , Humanos , Sistema Imunitário/virologia , Tegumento Comum/virologia , Rim/virologia , Sistema Musculoesquelético/virologia , Sistema Nervoso/virologia , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema Respiratório/virologia
14.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752138

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Sistema Imunitário/metabolismo , Peptidil Dipeptidase A/metabolismo , Fumar Tabaco , Adulto , Betacoronavirus/isolamento & purificação , Brônquios/citologia , Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Regulação para Cima , Adulto Jovem
16.
Int J Biol Sci ; 16(13): 2464-2476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760213

RESUMO

In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused infections worldwide. However, the correlation between the immune infiltration and coronavirus disease 2019 (COVID-19) susceptibility or severity in cancer patients remains to be fully elucidated. ACE2 expressions in normal tissues, cancers and cell lines were comprehensively assessed. Furthermore, we compared ACE2 expression between cancers and matched normal tissues through Gene Expression Profiling Interactive Analysis (GEPIA). In addition, we performed gene set enrichment analysis (GSEA) to investigate the related signaling pathways. Finally, the correlations between ACE2 expression and immune infiltration were investigated via Tumor Immune Estimation Resource (TIMER) and GEPIA. We found that ACE2 was predominantly expressed in both adult and fetal tissues from the digestive, urinary and male reproductive tracts; moreover, ACE2 expressions in corresponding cancers were generally higher than that in matched healthy tissues. GSEA showed that various metabolic and immune-related pathways were significantly associated with ACE2 expression across multiple cancer types. Intriguingly, we found that ACE2 expression correlated significantly with immune cell infiltration in both normal and cancer tissues, especially in the stomach and colon. These findings proposed a possible fecal-oral and maternal-fetal transmission of SARS-CoV-2 and suggested that cancers of the respiratory, digestive or urinary tracts would be more vulnerable to SARS-CoV-2 infection.


Assuntos
Biologia Computacional , Infecções por Coronavirus/imunologia , Neoplasias/imunologia , Pneumonia Viral/imunologia , Adulto , Betacoronavirus , Infecções por Coronavirus/complicações , Enterócitos/metabolismo , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Genótipo , Células Caliciformes/metabolismo , Hepatócitos/metabolismo , Humanos , Sistema Imunitário , Túbulos Renais/embriologia , Masculino , Neoplasias/complicações , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Prognóstico , RNA-Seq , Transdução de Sinais
17.
J Transl Med ; 18(1): 322, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847594

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D's non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here: 1. Vitamin D might aid in preventing SARS-CoV-2 infection: Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. Vitamin D: Overview of local immunomodulation in human infectious diseases. Anti-viral infection. Anti-malaria and anti-systemic lupus erythematosus (SLE). 2. Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19: Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF). 3. Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF): Vitamin D: Induction of key neurotrophic factors. .


Assuntos
Quimioprevenção/métodos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Imunomodulação/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vitamina D/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Suplementos Nutricionais , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/fisiologia , Neuroproteção/efeitos dos fármacos , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Vitamina D/metabolismo , Vitamina D/farmacologia , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/virologia
18.
PLoS Comput Biol ; 16(7): e1008051, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730250

RESUMO

In the animal kingdom, various forms of swarming enable groups of autonomous individuals to transform uncertain information into unified decisions which are probabilistically beneficial. Crossing scales from individual to group decisions requires dynamically accumulating signals among individuals. In striking parallel, the mammalian immune system is also a group of decentralized autonomous units (i.e. cells) which collectively navigate uncertainty with the help of dynamically accumulating signals (i.e. cytokines). Therefore, we apply techniques of understanding swarm behavior to a decision-making problem in the mammalian immune system, namely effector choice among CD4+ T helper (Th) cells. We find that incorporating dynamic cytokine signaling into a simple model of Th differentiation comprehensively explains divergent observations of this process. The plasticity and heterogeneity of individual Th cells, the tunable mixtures of effector types that can be generated in vitro, and the polarized yet updateable group effector commitment often observed in vivo are all explained by the same set of underlying molecular rules. These rules reveal that Th cells harness dynamic cytokine signaling to implement a system of quorum sensing. Quorum sensing, in turn, may confer adaptive advantages on the mammalian immune system, especially during coinfection and during coevolution with manipulative parasites. This highlights a new way of understanding the mammalian immune system as a cellular swarm, and it underscores the power of collectives throughout nature.


Assuntos
Percepção de Quorum , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Diferenciação Celular , Citocinas/imunologia , Tomada de Decisões , Humanos , Sistema Imunitário , Interferon gama/imunologia , Ativação Linfocitária , Modelos Teóricos , Probabilidade , Transdução de Sinais , Processos Estocásticos , Linfócitos T Auxiliares-Indutores/citologia , Células Th1/citologia , Células Th1/imunologia , Células Th2/citologia , Células Th2/imunologia
19.
Sci Total Environ ; 742: 140538, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-32634691

RESUMO

The broad utilisation of neonicotinoids, particularly imidacloprid (IMI), in agriculture has led to unplanned contamination of aquatic systems around the world. The sublethal effects of individual pesticides on the immune system of oysters, as well as their combined effects with other environmental stressors that fluctuate in estuarine environments, such as salinity, are yet to be investigated in ecotoxicology. We investigated the acute (4 d) toxicity of IMI in two salinity regimes on the immune parameters of Sydney rock oysters (SRO), including total hemocyte counts (THC), differential hemocyte counts (DHC), phagocytosis and hemocyte aggregation (HA), hemolymph protein expression and enzyme (catalase (CAT), glutathione S-transferase (GST) and acetylcholinesterase (AChE)) activities. Environmentally relevant concentrations of IMI were found to cause an increase in THC, induce GST activity, reduce HA, and inhibit AChE activity. However, DHC, CAT activity and phagocytosis were not significantly impacted at any test concentration at either salinity. IMI concentrations ≥0.01 mg/L significantly altered the expression of 28 proteins in the hemolymph of SRO, including an increase in the relative expression of extracellular superoxide dismutase, severin, ATP synthase subunit beta, as well as stress response proteins (heat shock proteins, serine/threonine-protein kinase DCLK3 and peroxiredoxin-1), and a decrease/absence of collagen alpha-4 (VI) and alpha-6 (VI) chain, metalloendopeptidase, L-ascorbate oxidase, transporter, CEP209_CC5 domain-containing protein and actin. This study indicates that the immune system of SRO can be impacted at environmentally relevant concentrations of IMI, but reduced salinity does not appear to influence the toxicity of this insecticide.


Assuntos
Inseticidas , Ostreidae , Animais , Sistema Imunitário , Neonicotinoides , Nitrocompostos , Salinidade
20.
PLoS One ; 15(7): e0234150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614830

RESUMO

To investigate a Florida manatee (Trichechus manatus latirostris) mortality event following a red tide bloom in Southwest Florida, an RNA sequencing experiment was conducted. Gene expression changes in white blood cells were assessed in manatees rescued from a red tide affected area (n = 4) and a control group (n = 7) using RNA sequencing. The genes with the largest fold changes were compared between the two groups to identify molecular pathways related to cellular and disease processes. In total, 591 genes (false discovery rate <0.05) were differentially expressed in the red tide group. Of these, 158 were upregulated and 433 were downregulated. This suggests major changes in white blood cell composition following an exposure to red tide. The most highly upregulated gene, Osteoclast associated 2C immunoglobulin-like receptor (OSCAR), was upregulated 12-fold. This gene is involved in initiating the immune response and maintaining a role in adaptive and innate immunity. The most highly downregulated gene, Piccolo presynaptic cytomatrix protein (PCLO), was downregulated by a factor of 977-fold. This gene is associated with cognitive functioning and neurotransmitter release. Downregulation of this gene in other studies was associated with neuronal loss and neuron synapse dysfunction. Among the cellular pathways that were most affected, immune response, including inflammation, wounds and injuries, cell proliferation, and apoptosis were the most predominant. The pathway with the most differentially expressed genes was the immune response pathway with 98 genes involved, many of them downregulated. Assessing the changes in gene expression associated with red tide exposure enhances our understanding of manatee immune response to the red tide toxins and will aid in the development of red tide biomarkers.


Assuntos
Perfilação da Expressão Gênica , Proliferação Nociva de Algas , Trichechus manatus/fisiologia , Animais , Buffy Coat/citologia , Florida , Ontologia Genética , Sistema Imunitário , Leucócitos/metabolismo , Toxinas Marinhas/envenenamento , Redes e Vias Metabólicas/genética , Neurotoxinas/envenenamento , Oxocinas/envenenamento , Envenenamento/sangue , Envenenamento/reabilitação , Envenenamento/veterinária , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , Transcriptoma , Trichechus manatus/sangue , Trichechus manatus/genética , Trichechus manatus/imunologia
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