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1.
Chem Biol Interact ; 337: 109379, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453195

RESUMO

Cadmium (Cd) is a toxic metal, which seems to be crucial during the prepubertal period. Cd can destroy the structural integrity of the blood-brain barrier (BBB) and enters into the brain. Although the brain is susceptible to neurotoxicity induced by Cd, the effects of Cd on the brain, particularly hypothalamic transcriptome, are still relatively poorly understood. Therefore, we investigated the molecular effects of Cd exposure on the hypothalamus by profiling the transcriptomic response of the hypothalamus to high dose of Cd (25 mg/kg bw/day cadmium chloride (CdCl2)) during the prepubertal period in Sprague-Dawley female rats. After sequencing and annotation, differential expression analysis revealed 1656 genes that were differentially expressed that 108 of them were classified into 37 transcription factor (TF) families. According to gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, these differentially expressed genes (DEGs) were involved in different biological processes and neurological disorders including Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), prolactin signaling pathway, PI3K/Akt signaling, and dopaminergic synapse. Five transcripts were selected for further analyses with Real-time quantitative PCR (RT-qPCR). The RT-qPCR results were mostly consistent with those from the high throughput RNA sequencing (RNA-seq). Cresyl violet staining clearly showed an increased neuronal degeneration in the dorsomedial hypothalamus (DMH) and arcuate (Arc) nuclei of the CdCl2 group. Overall, this study demonstrates that prepubertal exposure to high doses of Cd induces hypothalamic injury through transcriptome profiling alteration in female rats, which reveals the new mechanisms of pathogenesis of Cd in the hypothalamus.


Assuntos
Cloreto de Cádmio/toxicidade , Hipotálamo/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/patologia , Glicemia/análise , Regulação para Baixo/efeitos dos fármacos , Feminino , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/patologia , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Prolactina/sangue , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
2.
PLoS Negl Trop Dis ; 15(1): e0008895, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395417

RESUMO

A wide variety of symptoms is associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and these symptoms can overlap with other conditions and diseases. Knowing the distribution of symptoms across diseases and individuals can support clinical actions on timelines shorter than those for drug and vaccine development. Here, we focus on zinc deficiency symptoms, symptom overlap with other conditions, as well as zinc effects on immune health and mechanistic zinc deficiency risk groups. There are well-studied beneficial effects of zinc on the immune system including a decreased susceptibility to and improved clinical outcomes for infectious pathogens including multiple viruses. Zinc is also an anti-inflammatory and anti-oxidative stress agent, relevant to some severe Coronavirus Disease 2019 (COVID-19) symptoms. Unfortunately, zinc deficiency is common worldwide and not exclusive to the developing world. Lifestyle choices and preexisting conditions alone can result in zinc deficiency, and we compile zinc risk groups based on a review of the literature. It is also important to distinguish chronic zinc deficiency from deficiency acquired upon viral infection and immune response and their different supplementation strategies. Zinc is being considered as prophylactic or adjunct therapy for COVID-19, with 12 clinical trials underway, highlighting the relevance of this trace element for global pandemics. Using the example of zinc, we show that there is a critical need for a deeper understanding of essential trace elements in human health, and the resulting deficiency symptoms and their overlap with other conditions. This knowledge will directly support human immune health for decreasing susceptibility, shortening illness duration, and preventing progression to severe cases in the current and future pandemics.


Assuntos
/tratamento farmacológico , Zinco/administração & dosagem , Zinco/deficiência , Anti-Inflamatórios/farmacologia , /virologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Fatores de Risco , /isolamento & purificação
3.
Nat Commun ; 12(1): 132, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420104

RESUMO

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.


Assuntos
Poluentes Ambientais/efeitos adversos , Feto/imunologia , Exposição Materna/efeitos adversos , Sarampo/sangue , Praguicidas/efeitos adversos , Adulto , Anticorpos Antivirais/sangue , Pré-Escolar , Ensaios Clínicos Fase III como Assunto , Feminino , Sangue Fetal/química , Seguimentos , Humanos , Sistema Imunitário/efeitos dos fármacos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Malária/prevenção & controle , Troca Materno-Fetal/imunologia , Sarampo/imunologia , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Controle de Mosquitos/métodos , Praguicidas/análise , Fenilcarbamatos/efeitos adversos , Fenilcarbamatos/análise , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Ecotoxicol Environ Saf ; 211: 111947, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33503546

RESUMO

The chicken (Gallus gallus), which has three aryl hydrocarbon receptor (AHR) isoforms (ckAHR1, ckAHR2, and ckAHR1ß) and two AHR nuclear translocator (ARNT) isoforms (ckARNT1 and ckARNT2), is highly sensitive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and can serve as an avian model to gain an understanding of the mechanism underlying dioxin toxicity. To elucidate the mechanism of TCDD-induced immunotoxicity in avian species, we treated chicken embryos in ovo with graded concentrations of TCDD (1.5, 2.5, 3.0, 3.3, 3.5, and 4.0 µM). Initially, we measured mRNA expression levels of ckAHR and ckARNT isoforms and analyzed the T cell populations and transcriptome in the thymuses of TCDD-treated chicken embryos. Quantitative polymerase chain reaction analysis revealed that mRNA expressions of ckAHR1 and ckARNT2 were dominant in the thymus. Severe weight loss and thymus atrophy were observed in the TCDD-treated embryos. Immunophenotyping analyses demonstrated significant increases in CD4+CD8-CD25+ and CD4+CD8+CD25+ regulatory T cells (Tregs) populations following TCDD exposure, suggesting that TCDD suppresses T cell-mediated immune responses in chicken embryos. In addition, thymic transcriptome analyses intimated that alteration of the signaling pathways related to erb-b2 receptor tyrosine kinase 4 (ERBB4) and wnt family member 5A (WNT5A), and bone morphogenetic protein (BMP) may be associated with the TCDD-induced thymus atrophy. We also observed significantly altered expression levels of genes including interleukine 13 receptor subunit alpha 2 (IL13RA2), transforming growth factor beta 1 (TGFß1), collagen type III alpha 1 chain (COL3A1), and collagen type IX alpha 3 chain (COL9A3), implying immunosuppression, fibrosis development, and collagen deposition. Collectively, these findings suggest that TCDD exposure activates the ckAHR1-ckARNT2 signaling pathway and suppresses immune responses through the prompted differentiation to CD4+CD8-CD25+ and CD4+CD8+CD25+ Tregs and altered expressions of immune-related genes in the thymus of chicken embryos.


Assuntos
Poluentes Ambientais/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular , Embrião de Galinha , Galinhas/metabolismo , Sistema Imunitário/efeitos dos fármacos , Isoformas de Proteínas/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Linfócitos T , Transcriptoma
5.
Maturitas ; 143: 1-9, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33308613

RESUMO

The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. Infection can cause fever, dry cough, fatigue, severe pneumonia, respiratory distress syndrome and in some instances death. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. There are currently no effective anti-SARS-CoV-2 viral drugs or vaccines. COVID-19 disproportionately affects the elderly, both directly, and through a number of significant age-related comorbidities. Undoubtedly, nutrition is a key determinant of maintaining good health. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19. In this paper, evidence surrounding the role of these dietary components in immunity as well as their specific effect in COVID-19 patients are discussed. In addition, how supplementation of these nutrients may be used as therapeutic modalities potentially to decrease the morbidity and mortality rates of patients with COVID-19 is discussed.


Assuntos
/tratamento farmacológico , Vitaminas/uso terapêutico , Ácido Ascórbico/imunologia , Ácido Ascórbico/uso terapêutico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Sistema Imunitário/efeitos dos fármacos , Selênio/imunologia , Selênio/uso terapêutico , Vitamina D/imunologia , Vitamina D/uso terapêutico , Vitamina E/imunologia , Vitamina E/uso terapêutico , Vitaminas/imunologia , Zinco/imunologia , Zinco/uso terapêutico
6.
Biomed Pharmacother ; 134: 111157, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33370631

RESUMO

Autoimmune diseases (AUDs) are a multifactorial disease, among which rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis are more prevalent. Several anti-inflammatory, biologics, and AUD-modifying drugs are found effective against them, but their repeated use are associated with various adverse effects. In this review article, we have focused on the regulation of inflammatory molecules, molecular signaling pathways, immune cells, and epigenetics by natural product thymoquinone on AUDs. Studies indicate that thymoquinone can regulate inflammatory molecules including interferons, interleukins, tumor necrosis factor-α (TNF-α), oxidative stress, regulatory T cells, and various signaling pathways such as nuclear factor kappa beta (NF-κß), janus kinase/signal transduction and activator of transcription (JAK-STAT), mitogen-activated protein kinase (MAPK) at the molecular level and epigenetic alteration. As these molecules and signaling pathways with defective immune function play an important role in AUD development, controlling these molecules and deregulated molecular mechanism is a significant feature of AUD therapeutics. Interestingly thymoquinone is reported to possess all these potential. This article reviewed the deregulated mechanism of AUDs, and the action of thymoquinone on inflammatory molecules, immune cells, signaling pathways, and epigenetic machinery. Thymoquinone can be regarded as a potential drug candidate for AUD treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Autoimunidade/efeitos dos fármacos , Benzoquinonas/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/fisiopatologia , Benzoquinonas/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Fatores Imunológicos/efeitos adversos , Mediadores da Inflamação/metabolismo , Transdução de Sinais
7.
Food Chem ; 340: 127933, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32882476

RESUMO

Polysaccharides are the most abundant bioactive compounds in Ganoderma and have been widely used as dietary supplements in traditional Chinese medicine for thousands of years. Polysaccharides from Ganoderma exhibit unique biological properties, including anti-tumor, anti-inflammatory, and immunomodulatory activities. Herein, the sources and structures of polysaccharides from Ganoderma were presented. This work also reviews the immunomodulatory activities and possible mechanisms of polysaccharides from Ganoderma on different immune effector cells, including lymphocytes and myeloid cells. As an available adjunctive remedy, polysaccharides from Ganoderma can potentially be applied for the modulation of the host immune system, namely the innate immunity, the cellular immunity, and the humoral immunity.


Assuntos
Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Ganoderma/química , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Animais , Antineoplásicos Imunológicos/farmacologia , Polissacarídeos Fúngicos/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia
8.
Ecotoxicol Environ Saf ; 207: 111527, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254397

RESUMO

Tetrachlorobisphenol A (TCBPA) is used as flame retardant, and it has been widely detected in the environmental and human samples. TCBPA is an endocrine disrupting chemical, but its effects on the immune system remains poorly understood. Here the effects of TCBPA on immune system were studied using combined in vivo and in vitro assays. Results showed that TCBPA could suppress the immune response in BALB/c mice via reducing the ratio of CD3+ T lymphocytes to regulatory T cells. Moreover, TCBPA exposure significantly induced the increasing secretion of four pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) and four anti-inflammatory cytokines (IL-4, IL-5, IL-10, GM-CSF) in mice serum. Interestingly, uterine edema was observed in over 80% TCBPA-treated mice after 14- day exposure. TCBPA was detected in 18.6% serum samples of 150 female volunteers in this study. Therefore, our findings provided evidence that TCBPA exposure may cause adverse outcomes on immune system and uterus, suggesting that environmental exposure of TCBPA, as well as its adverse effects on human health should be of concern.


Assuntos
Anti-Inflamatórios/farmacologia , Clorofenóis/farmacologia , Sistema Imunitário/efeitos dos fármacos , Animais , Citocinas , Feminino , Retardadores de Chama , Humanos , Imunossupressão , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Linfócitos T , Útero
9.
J Immunoassay Immunochem ; 41(6): 976-999, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356860

RESUMO

At present, specific therapies for COVID-19 are not well established, being certain only that the immune system plays a decisive role in the initiation and progression of the disease. Plants have given and continue to give compounds with great efficiency and low toxicity, some of them being a starting point for extremely effective synthetic substances. Although herbal remedies are used mainly for preventive purposes, there are also guidelines issued by some countries that indicate the use of traditional remedies for different stages of COVID-19 disease.Europe has a long and strong tradition of using medicinal plants for therapeutic purposes, but clinical trials for this type of approach are scarce, compared to Asia. In this regard, a bridge between tradition and science, would have a strong impact on the capacity for prevention and treatment of COVID-19. The paper reviews compounds of plant origin that have previously proven effective in counteracting some coronaviruses but also some of their major effects - direct action on virus replicative apparatus (viral entry or replication, action on the viral enzymatic system), collateral action of natural compounds on the immune system and also the contribution of herbal medicine as vaccine adjuvants are tackled.


Assuntos
/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Preparações de Plantas/uso terapêutico , Plantas Medicinais/química , /efeitos dos fármacos , Ensaios Clínicos como Assunto , Europa (Continente) , Humanos , Sistema Imunitário/efeitos dos fármacos , Lectinas/química , Óleos Voláteis/química , Fenóis/química , Fitoterapia , Saponinas/química , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
10.
Molecules ; 25(22)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207753

RESUMO

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.


Assuntos
Ácido Ascórbico/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Suplementos Nutricionais , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Selênio/uso terapêutico , Vitamina D/uso terapêutico , Anticorpos Antivirais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/dietoterapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Micronutrientes/uso terapêutico , Pneumonia Viral/dietoterapia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/virologia
11.
Nutrients ; 12(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003648

RESUMO

The third coronavirus outbreak in the last two decades has caused significant damage to the world's economy and community health. The highly contagious COVID-19 infection has affected millions of people to date and has led to hundreds of thousands of deaths worldwide. Aside from the highly infectious nature of SARS-CoV-2, the lack of a treatment or vaccine has been the main reason for its spread. Thus, it has become necessary to find alternative methods for controlling SARS-CoV-2. For the present review, we conducted an online search for different available nutrition-based therapies for previously known coronavirus infections and RNA-based virus infections as well as general antiviral therapies. These treatments have promise for combating COVID-19, as various nutrients and minerals play direct and indirect roles in the control and prevention of this newly emerged viral infection. The patients' nutritional status with COVID-19 must be analyzed before administering any treatment, and nutritional supplements should be given to the affected individuals along with routine treatment. We suggest a potential interventional role of nutrients to strengthen the immune system against the emerging infection caused by COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Sistema Imunitário/efeitos dos fármacos , Minerais/farmacologia , Pneumonia Viral/imunologia , Oligoelementos/farmacologia , Vitaminas/farmacologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Suplementos Nutricionais , Humanos , Sistema Imunitário/fisiologia , Micronutrientes , Minerais/uso terapêutico , Estado Nutricional , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave , Oligoelementos/uso terapêutico , Vitaminas/uso terapêutico
12.
Mol Biol Rep ; 47(10): 8229-8233, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32920757

RESUMO

COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Antivirais/uso terapêutico , Basigina/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Antivirais/farmacologia , Basigina/antagonistas & inibidores , Infecções por Coronavirus/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Melatonina/farmacologia , Pandemias , Pneumonia Viral/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
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
14.
Georgian Med News ; (303): 167-173, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32841200

RESUMO

Antibiotic resistance and its impact on human microbiome remains a global public health concern. Studies have shown that treatment with antibiotics leads to dramatic changes in composition and function of gut microbiome. This review focuses on the association between antibiotics use and its impact on gut microbiome of adults and children, gut microbiota metabolic interactions and presents the current understanding of the link between human gut microbiome and immune system.


Assuntos
Microbioma Gastrointestinal , Microbiota , Adulto , Antibacterianos/uso terapêutico , Criança , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Sistema Imunitário/efeitos dos fármacos
15.
Ecotoxicol Environ Saf ; 204: 111109, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32798751

RESUMO

Microplastic (MP) pollution of the marine environment is now a growing global concern posing a threat to a variety of species through the ingestion and transfer within food webs. This is considered a potential toxicological threat to marine species due to the chemical additives used to make many plastic products, or the persistent organic pollutants that may accumulate on them while residing in the environment. While the presence of MPs in the marine environment is widely documented, there are no other review articles providing a summary of published effect studies of MPs on the immune and reproductive systems of marine species. This manuscript reviews reproductive and immune-system changes in response to MPs in 7 and 9 species, respectively. Some species such as Mytilus galloprovincialis and oyster Crassostrea gigas were investigated in multiple papers. Most studies have been conducted on invertebrates, and only 3 studies have been performed on vertebrates, with exposure times ranging between 30 min and 60 days. A review of the literature revealed that the most common MPs types studied in relation to adverse impacts on immune system and reproductive success in marine species were polystyrene (PS) and polyethylene (PE). The immune system's responses to MPs exposure varied depending on the species, with altered organismal defense mechanisms and neutrophil function observed in fish and changes in lysosomal membrane stability and apoptotic-like nuclear alterations in phagocytes reported in invertebrate species. Reproductive responses to MPs exposure, varied depending on species, but included significant reduction in gamete and oocyte quality, fecundity, sperm swimming speed, and quality of offspring. The lack of published data means that developing a clear understanding of the impact across taxonomic groups with different feeding and behavioral traits is often difficult. Further work is required to better understand the risk MPs pose to the immune and reproductive systems of marine species in order to fully evaluate the impact these ubiquitous pollutants are having on marine ecosystems and the associated goods and services they provide.


Assuntos
Genitália/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Crassostrea , Ecossistema , Monitoramento Ambiental , Poluentes Ambientais/farmacologia , Poluição Ambiental , Peixes , Cadeia Alimentar , Genitália/química , Invertebrados , Microplásticos/análise , Mytilus/efeitos dos fármacos , Plásticos , Polietileno , Poliestirenos , Poluentes Químicos da Água/análise
16.
Placenta ; 99: 117-130, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798764

RESUMO

The current challenge of the COVID-19 pandemic is complicated by the limited therapeutic options against the virus, with many being anecdotal or still undergoing confirmatory trials, underlining the urgent need for novel strategies targeting the virus. The pulmotropic virus causes loss of oxygenation in severe cases with acute respiratory distress syndrome (ARDS) and need for mechanical ventilation. This work seeks to introduce placental extract-derived biologically active components as a therapeutic option and highlights their mechanism of action relevant to COVID-19 virus. Human placenta has been used in clinical practice for over a century and there is substantial experience in clinical applications of placental extract for different indications. Aqueous extract of human placentacontains growth factors, cytokines/chemokines, natural metabolic and other compounds, anti-oxidants, amino acids, vitamins, trace elements and biomolecules, which individually or in combination show accelerated cellular metabolism, immunomodulatory and anti-inflammatory effects, cellular proliferation and stimulation of tissue regeneration processes. Placental extract treatment is proposed as a suitable therapeutic approach consideringthe above properties which could protect against initial viral entry and acute inflammation of alveolar epithelial cells, reconstitute pulmonary microenvironment and regenerate the lung. We reviewed useful therapeutic information of placental biomolecules in relation to COVID-19 treatment. We propose the new approach of using placental growth factors, chemokines and cytokine which will execute antiviral activity in coordination with innate and humoral immunity and improve patient's immunological responses to COVID-19. Executing a clinical trial using placental extract as preventive, protective and/or therapeutic approach for COVID-19treatment could advance the development of a most promising therapeutic candidate that can join the armamentaria against the COVID-19 virus.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Fator de Crescimento Placentário/uso terapêutico , Placenta/química , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios , Antivirais , Betacoronavirus/patogenicidade , Quimiocinas/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Citocinas/uso terapêutico , Feminino , Humanos , Sistema Imunitário/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Gravidez , Receptores Virais
17.
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
18.
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
19.
Int. j. morphol ; 38(4): 1032-1038, Aug. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1124893

RESUMO

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.


El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.


Assuntos
Animais , Dexametasona/farmacologia , Sistema Imunitário/efeitos dos fármacos , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Galinhas , Cloaca/efeitos dos fármacos
20.
Curr Pharm Des ; 26(35): 4467-4485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634079

RESUMO

Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds have been used as antimalarial agents for many years. Currently, they are used as monotherapy or in conjunction with other therapies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). Based on its effects on the modulation of the autophagy process, various clinical studies suggest that CQ and HCQ could be used in combination with other chemotherapeutics for the treatment of various types of cancer. Furthermore, the antiviral effects showed against Zika, Chikungunya, and HIV are due to the annulation of endosomal/lysosomal acidification. Recently, CQ and HCQ were approved for the U.S. Food and Drug Administration (FDA) for the treatment of infected patients with the coronavirus SARSCoV- 2, causing the disease originated in December 2019, namely COVID-2019. Several mechanisms have been proposed to explain the pharmacological effects of these drugs: 1) disruption of lysosomal and endosomal pH, 2) inhibition of protein secretion/expression, 3) inhibition of antigen presentation, 4) decrease of proinflammatory cytokines, 5) inhibition of autophagy, 6) induction of apoptosis and 7) inhibition of ion channels activation. Thus, evidence has shown that these structures are leading molecules that can be modified or combined with other therapeutic agents. In this review, we will discuss the most recent findings in the mechanisms of action of CQ and HCQ in the immune system, and the use of these antimalarial drugs on diseases.


Assuntos
Cloroquina/farmacologia , Hidroxicloroquina/farmacologia , Sistema Imunitário/efeitos dos fármacos , Doenças Autoimunes/tratamento farmacológico , Betacoronavirus , Cloroquina/uso terapêutico , Infecções por Coronavirus , Humanos , Hidroxicloroquina/uso terapêutico , Pandemias , Pneumonia Viral
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