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1.
Urol Clin North Am ; 47(4): 413-417, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008492

RESUMO

In recent years, immunotherapy has been the focus of great interest to researchers, clinicians, and the general public. Traditionally cancer therapy has been thought to be limited to surgery, radiation therapy, or chemotherapy. Some clinicians have considered it the so-called fifth pillar of cancer therapy, following surgery, cytotoxic chemotherapy, radiation, and targeted therapy. However, the origins of immunotherapy in cancer treatment reach back at least into the nineteenth century. This article reviews the origins, development, and future of immunotherapy.


Assuntos
Fatores Imunológicos/administração & dosagem , Imunoterapia/métodos , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , História do Século XIX , Humanos , Imunoterapia/história , Estados Unidos , Neoplasias Urológicas/patologia
2.
Urol Clin North Am ; 47(4): 443-456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008495

RESUMO

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Discov Med ; 29(158): 145-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007190

RESUMO

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Oftalmopatias/virologia , Pneumonia Viral/complicações , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Reposicionamento de Medicamentos , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Oftalmopatias/terapia , Humanos , Imunização Passiva/métodos , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa/métodos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
5.
BMJ Case Rep ; 13(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958554

RESUMO

Clinical manifestations of COVID-19 are known to be variable with growing evidence of nervous system involvement. In this case report, we describe the symptoms of a patient infected with SARS-CoV-2 whose clinical course was complicated with Guillain-Barré syndrome (GBS). We present a case of a 58-year-old woman who was initially diagnosed with COVID-19 pneumonia due to symptoms of fever and cough. Two weeks later, after the resolution of upper respiratory tract symptoms, she developed symmetric ascending quadriparesis and paresthesias. The diagnosis of GBS was made through cerebrospinal fluid analysis and she was successfully treated with intravenous immunoglobulin administration.


Assuntos
Infecções por Coronavirus/complicações , Síndrome de Guillain-Barré/fisiopatologia , Dor Lombar/fisiopatologia , Debilidade Muscular/fisiopatologia , Parestesia/fisiopatologia , Pneumonia Viral/complicações , Analgésicos/uso terapêutico , Betacoronavirus , Encéfalo/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico , Diagnóstico Diferencial , Feminino , Gabapentina/uso terapêutico , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Vértebras Lombares/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Radiculopatia/diagnóstico , Medula Espinal/diagnóstico por imagem
7.
Am J Chin Med ; 48(6): 1315-1330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907362

RESUMO

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/tratamento farmacológico , Sepse/tratamento farmacológico , Artemisininas/uso terapêutico , Astragalus propinquus , Berberina/uso terapêutico , Betacoronavirus , Estado Terminal , Emodina/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Mucosa Intestinal , Microcirculação , Pandemias , Permeabilidade , Rheum , Salvia miltiorrhiza
8.
Nutrients ; 12(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967126

RESUMO

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.


Assuntos
Fatores Imunológicos/uso terapêutico , Viroses/terapia , Deficiência de Vitamina D/terapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Suplementos Nutricionais , Humanos , Sistema Imunitário , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/imunologia , Viroses/virologia , Vitamina D/sangue , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/virologia
9.
Int J Mol Sci ; 21(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957696

RESUMO

At present, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has quickly become a health emergency because no specifics vaccines or drugs, at this moment, are available. Recent studies have shown that the transplantation of mesenchymal stem cells (MSCs) into Coronavirus Disease 2019 (COVID-19) patients could represent a promising strategy for the development of new therapeutic methods. We speculate and suggest that the secretome of human Oral Tissue Stem Cells (hOTSCs), for their immunomodulatory and anti-inflammatory specific properties, could exert beneficial effects on the COVID-19 patients through an innovative aerosolisation technique. This non-invasive technique can offer multiple advantages in prophylaxis, as well as the prevention and treatment of severe epidemic respiratory syndrome with minimum risk and optimal therapeutic effects. This has the potential to create a novel pathway towards immunomodulatory therapy for the treatment of COVID-19 positive patients.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Mucosa Bucal/citologia , Pneumonia Viral/tratamento farmacológico , Proteoma/uso terapêutico , Humanos , Fatores Imunológicos/metabolismo , Pandemias , Proteoma/metabolismo , Via Secretória
11.
Viruses ; 12(9)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967229

RESUMO

As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.


Assuntos
Fatores Imunológicos/imunologia , Viroses/imunologia , Vírus/imunologia , Animais , Antivirais/uso terapêutico , Doença Crônica , Humanos , Fatores Imunológicos/antagonistas & inibidores , Imunoterapia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Viroses/terapia , Vírus/classificação
12.
Rinsho Ketsueki ; 61(8): 912-921, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908055

RESUMO

Although multiple myeloma has been defined as incurable, and the treatment outcome has recently improved rapidly. Antibodies against multiple myeloma, elotuzumab, and daratumumab can safely enhance their effects even when added to the combination therapy of proteasome inhibitors and immunomodulators that have been used till date. Initially, triplet therapy combining antibody therapy with doublet therapy was approved in Japan for relapsed or refractory multiple myeloma. In 2019, daratumumab combination therapies were approved for newly diagnosed multiple myeloma patients, and these therapies are the new standard of care. Recently, the results of clinical trials that added daratumumab to the triplet therapies of proteasome inhibitors, immunomodulators, and dexamethasone have been reported. These trials report greater therapeutic effects, with a significant improvement in the MRD negative rate. We hope that quadruplet therapy including these antibodies will be available in clinical practice, leading to further improvements in the treatment outcomes.


Assuntos
Anticorpos/uso terapêutico , Mieloma Múltiplo , Humanos , Fatores Imunológicos , Japão , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteassoma , Radioimunoterapia
13.
Trials ; 21(1): 766, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891160

RESUMO

OBJECTIVES: To investigate the potential efficacy of Acacia Senegal extract Gum Arabic (GA) supplementation as immunomodulatory and anti-inflammatory dietary intervention among newly diagnosed COVID 19 Sudanese patients. To study the effect of GA on the level of cytokines, TNFα, IL8, IL6 IL10, CRP and the viral load. Secondary outcomes will be the effect of GA oral intake on mortality rate and days of hospital admission. TRIAL DESIGN: Quadruple blind, randomized placebo-controlled clinical trial Phase II & III. Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio) superiority trial of oral GA among seropositive COVID-19 patients. PARTICIPANTS: Inclusion criteria: COVID-19 infected (newly diagnosed) as proved by real-time PCR within 72 hours of PCR. Age 8-90 years Both genders Exclusion criteria: Intubated patients on parenteral treatment Allergy to Gum Arabic The study will be conducted in COVID Isolation Centres and Soba University Hospital Khartoum State Sudan. INTERVENTION AND COMPARATOR: Experimental: Intervention Group This arm will receive 100% natural Gum Arabic provided in a powder form in 30-grams-dose once daily for four weeks Placebo Comparator: Control group: This group will be provided with pectin powder provided as one-gram-dose once daily for four weeks Both GA and placebo will be in addition to standard care treatment based on local clinical guidelines. MAIN OUTCOMES: Mean change from baseline score of Immune Response to end of the trial. Changes of the level of Tumor Necrosis Factor (TNFα), interleukin IL8, IL6, and IL10 from the baseline values (Four weeks from the start of randomization). Mortality rate: The percentage of deaths among COVID 19 patients received Gum Arabic compared to placebo (Four weeks from the start of randomization]). RANDOMISATION: Randomization (1:1 allocation ratio) and will be conducted using a sequence of computer-generated random numbers by an independent individual. Each participating centre will be assigned a special code generated by the computer. The randomization will be kept by the PI and a research assistant. BLINDING (MASKING): Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 110 eligible patients will be randomly assigned to either GA (n=55) or placebo (n=55) groups. TRIAL STATUS: Protocol Version no 2, 30th June 2020. Recruitment will start on 15th September 2020. The intended completion date is 15th January 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04381871 . Date of trial registration: 11 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Goma Arábica/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Criança , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Goma Arábica/efeitos adversos , Interações entre Hospedeiro e Microrganismos , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Molecules ; 25(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987757

RESUMO

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Peptídeos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Fármacos do Sistema Respiratório/uso terapêutico , Doença Aguda , Anti-Inflamatórios/síntese química , Antivirais/síntese química , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Fatores Imunológicos/síntese química , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Peptídeos/síntese química , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Insuficiência Respiratória/complicações , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/prevenção & controle , Insuficiência Respiratória/virologia , Fármacos do Sistema Respiratório/síntese química , Relação Estrutura-Atividade
15.
J Infect Dev Ctries ; 14(8): 844-846, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32903227

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China, on Jan 7, 2020. Over the following months, the virus rapidly spread throughout the world. Coronavirus Disease 2019 (COVID-19) can involve the gastrointestinal tract, including symptoms like nausea, vomiting and diarrhea and shedding of the SARS-CoV-2 in feces. Angiotensin-converting enzyme 2 (ACE2) protein, which has been proven to be a cell receptor for SARS-CoV-2, is expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells. According to the literature, rates of COVID-19 patients reporting diarrhea were between 7 - 14%. Diarrhea in the course of COVID-19 disease can cause dehydration and hospitalization. Although no antiviral drug was specifically designed for the treatment of diarrhea, several molecules could have beneficial effects by reducing viral replication. In this letter, we discussed the Levamisole, which is an anthelmintic agent with immunomodulatory effects, could be used effectively both for antiviral therapy and especially in COVID-19 patients with diarrhea.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Diarreia/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Levamisol/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/complicações , Humanos , Pandemias , Pneumonia Viral/complicações
16.
Acta Biomed ; 91(3): e2020038, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921732

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that mainly affects the upper and lower respiratory tract and is responsible for extremely different degrees of disease, ranging from flu-like symptoms to atypical pneumonia that may evolve to acute respiratory distress syndrome and, ultimately, death. No specific therapy for SARS-CoV-2 has yet been identified, but since the beginning of the outbreak, several pre-existing therapeutics have been reconsidered for the treatment of infected patients. The aim of this article is to discuss current therapeutics against SARS-CoV-2. A literature review was performed using PubMed, collecting data from English-language articles published until June 20th, 2020. Literature analysis showed that with the acquisition of more in-depth knowledge on the characteristics of SARS-CoV-2 and the pathogenesis of the different clinical manifestations, a more rationale use of available drugs has become possible. However, the road to defining which drugs are effective and which schedules of administration must be used to maximize efficacy and minimize adverse events is still very long. To date, it is only clear that no drug can alone cope with all the problems posed by SARS-CoV-2 infection and effective antivirals and inflammatory drugs must be given together to reduce COVID-19 clinical manifestations. Moreover, choice of therapy must always be tailored on clinical manifestations and, when they occur, drugs able to fight coagulopathy and venous thromboembolism that may contribute to respiratory deterioration must be prescribed.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Humanos
17.
Int J Med Sci ; 17(14): 2133-2146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922174

RESUMO

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Descoberta de Drogas , Melatonina/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Cisteína Endopeptidases , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Melatonina/uso terapêutico , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico
18.
APMIS ; 128(11): 583-592, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32865844

RESUMO

Multiple sclerosis (MS) is an immune-mediated inflammatory disease which affects the central nervous system (CNS). In the present study, the in vivo effects of ATRA, calcitriol, and their combinations on the expression of murine CD4+ T cell cytokines and their specific transcription factors in experimental autoimmune encephalomyelitis (EAE)-induced mice were explored. Thirty-two EAE induced inbred C57BL/6 female mice with an age ranged from 8 to 10 weeks were divided into four categories in a random manner. The first, second, and third groups received ATRA, calcitriol, ATRA+ calcitriol, respectively, and the fourth group received vehicle. The treatment started on the day prior to immunization and through the IP injections every other days for 21 days. The dosages of administration for calcitriol, ATRA, and calcitriol+ ATRA were 100 ng, 250 µg, and 50ng + 125 µg, respectively per mouse. An equal volume of excipient was administered for the vehicle group. T-bet, IFN-γ, GATA-3, and IL-4 genes expression were assessed in the splenocytes of EAE -induced mice. The expression of T-bet and IFN-γ genes in the splenocytes of ATRA, calcitriol and combination- treated mice were significantly reduced compared to vehicle group (p < 0.05). A significant decrease in T-bet expression was observed in the combination-treated group compared to the ATRA-treated group (p < 0.05). The expression of GATA3 and IL-4 genes was significantly increased in the ATRA-, calcitriol-, and combination-treated mice when compared with the control group (p < 0.05). Furthermore, the effect of calcitriol alone and in combination with ATRA was more considerable than that of ATRA alone. The nutraceutical approaches may be promising in the prevention and/or treatment of MS.


Assuntos
Calcitriol/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Tretinoína/farmacologia , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Esquema de Medicação , Quimioterapia Combinada , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Transdução de Sinais , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia
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