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1.
Gene ; 806: 145921, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454033

RESUMO

Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a ß-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via ß-adrenergic receptors in vivo.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Interleucina-10/genética , Extratos Vegetais/farmacologia , Receptores Adrenérgicos beta/genética , Administração Oral , Animais , Modelos Animais de Doenças , Efedrina/farmacologia , Regulação da Expressão Gênica , Injeções Intraperitoneais , Interleucina-10/agonistas , Interleucina-10/imunologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poli I-C/administração & dosagem , Poli I-C/antagonistas & inibidores , Receptores Adrenérgicos beta/imunologia , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
2.
J Ethnopharmacol ; 282: 114574, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34461187

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gekko gecko is used as a traditional medicine for various diseases including respiratory disorders in northeast Asian countries, mainly Korea, Japan, and China. AIM OF THE STUDY: Allergic asthma is a chronic respiratory disease caused by an inappropriate immune response. Due to the recent spread of coronavirus disease 2019, interest in the treatment of pulmonary disorders has rapidly increased. In this study, we investigated the anti-asthmatic effects of G. gecko extract (GGE) using an established mouse model of ovalbumin-induced asthma. MATERIALS AND METHODS: To evaluate the anti-asthmatic effects of GGE, we evaluated histological changes and the responses of inflammatory mediators related to allergic airway inflammation. Furthermore, we investigated the regulatory effects of GGE on type 2 helper T (Th2) cell activation. RESULTS: Administration of GGE attenuated asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and expression of Th2 cytokines. Furthermore, GGE treatment reduced Th2 cell activation and differentiation. CONCLUSIONS: These results indicate that GGE alleviates allergic airway inflammation by regulating Th2 cell activation and differentiation.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medicina Tradicional do Leste Asiático , Muco/metabolismo , Ovalbumina , Extratos Vegetais/uso terapêutico , Animais , Asma/induzido quimicamente , Asma/patologia , Líquido da Lavagem Broncoalveolar , COVID-19 , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Triptaminas/farmacologia
3.
Anticancer Res ; 41(10): 5157-5163, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593467

RESUMO

BACKGROUND/AIM: Adjuvant platinum-based chemotherapy (APC) has been the standard of care for patients with non-small-cell lung cancer (NSCLC) who have undergone complete pulmonary resection. This study analyzed the clinical and prognostic significance of immunonutritional indices in NSCLC patients receiving APC. PATIENTS AND METHODS: We retrospectively reviewed 110 patients from 2008 to 2016. Three immunonutritional indices were calculated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI). RESULTS: The median age was 64 years, and 66 patients were males. Each index showed a significant correlation with primary tumor length. NLR and PLR were significantly correlated with vascular invasion. Prognostic analyses revealed that each index was significantly correlated with postoperative recurrence-free survival (RFS) and overall survival (OS). On multivariate analyses, PNI was an independent predictor of RFS and OS. CONCLUSION: Host immunonutritional status may have a significant effect on the postoperative prognosis of NSCLC in patients receiving APC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Estado Nutricional , Compostos Organoplatínicos/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Nat Commun ; 12(1): 5730, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593807

RESUMO

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.


Assuntos
COVID-19/transmissão , Evasão da Resposta Imune/genética , Modelos Biológicos , Pandemias/estatística & dados numéricos , SARS-CoV-2/patogenicidade , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Simulação por Computador , Previsões/métodos , Humanos , Pessoa de Meia-Idade , Mutação , Pandemias/prevenção & controle , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Processos Estocásticos , Reino Unido/epidemiologia , Vacinação/estatística & dados numéricos , Adulto Jovem
5.
PLoS Med ; 18(10): e1003769, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34597298

RESUMO

BACKGROUND: NVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS AND FINDINGS: The phase 2 component of our randomized, placebo-controlled, phase 1 to 2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late-phase studies and was based on immunogenicity and safety data through Day 35 (14 days after the second dose). The trial was conducted at 9 sites in Australia and 8 sites in the United States. Participants in 2 age groups (aged 18 to 59 and 60 to 84 years) were randomly assigned to receive either 1 or 2 intramuscular doses of 5-µg or 25-µg NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response. After enrollment, 1,288 participants were randomly assigned to 1 of 4 vaccine groups or placebo, with 1,283 participants administered at least 1 study treatment. Of these, 45% were older participants 60 to 84 years. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose. Reactogenicity occurred less frequently and was of lower intensity in older participants. Both 2-dose regimens of 5-µg and 25-µg NVX-CoV2373 induced robust immune responses in younger and older participants. For the 2-dose regimen of 5 µg, geometric mean titers (GMTs) for IgG anti-spike protein were 65,019 (95% confidence interval (CI) 55,485 to 76,192) and 28,137 (95% CI 21,617 to 36,623) EU/mL and for wild-type virus neutralizing antibody (with an inhibitory concentration of 50%-MN50%) were 2,201 (95% CI 1,343 to 3,608) and 981 (95% CI 560 to 1,717) titers for younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in a panel of convalescent sera for both age groups. Study limitations include the relatively short duration of safety follow-up to date and current lack of immune persistence data beyond the primary vaccination regimen time point assessments, but these data will accumulate over time. CONCLUSIONS: The study confirmed the phase 1 findings that the 2-dose regimen of 5-µg NVX-CoV2373 is highly immunogenic and well tolerated in younger adults. In addition, in older adults, the 2-dose regimen of 5 µg was also well tolerated and showed sufficient immunogenicity to support its use in late-phase efficacy studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04368988.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Imunogenicidade da Vacina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
6.
Anticancer Res ; 41(10): 4895-4905, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593437

RESUMO

BACKGROUND/AIM: The limited efficacy of immune checkpoint inhibitors in colorectal cancer (CRC) is likely due to immunosuppressive mechanisms including T cell exhaustion caused by inhibitory immune checkpoints in the tumor microenvironment. MATERIALS AND METHODS: We investigated the expression status of the inhibitory immune checkpoint receptors on tumor-infiltrating T cells and their ligands on tumor cells by flow cytometry and immunohistochemistry, using surgically-resected specimens of CRC. RESULTS: Flow cytometry analysis indicated that TIM-3, TIGIT, and PD-1 were expressed on tumor-infiltrating CD4+ (8.3%, 56.0%, 26.1%) and CD8+ T cells (8.2%, 51.6%, 23.5%), and CRC cells abundantly expressed PD-L1, CEACAM-1, and CD155 (2.2%, 77.0%, 46.8%). Immunohistochemical analysis revealed that the tumor proportional score of PD-L1, CEACAM-1, and CD155 was 42.4%, 54.2%, and 52.1%, respectively. CONCLUSION: PD-1, TIM-3, and TIGIT axes may reduce T cell function in the CRC tumor microenvironment.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Checkpoint Imunológico/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Receptores Imunológicos/metabolismo , Microambiente Tumoral/imunologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Anticancer Res ; 41(10): 4907-4916, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593438

RESUMO

BACKGROUND: Interleukin-6 receptor antibody (IL6R) inhibits colony formation and invasion by colorectal carcinoma (CRC) in vitro. We examined the effect of IL6R antibody on tumor growth of CRC xenografts in vivo. MATERIALS AND METHODS: SW480 cells inoculated subcutaneously into NU/NU mice were treated with anti-IL6R and tumor histology and growth-related signaling were subsequently estimated by hematoxylin and eosin and immunohistochemical staining. RESULTS: Tumor growth was inhibited by anti-IL6R treatment at dosages of both 0.1 and 1.0 mg/kg. Tumor cells had invaded into surrounding tissues in untreated mice, while there was no invasion of tumors in the IL6R antibody-treated mice. The expression of Ki-67, signal transducer and activator of transcription protein 3 (STAT3) and phosphor-extracellular signal-regulated kinase 1 and 2 (ERK1/2) were suppressed in anti-IL6R-treated tumors. CONCLUSION: IL6R antibody inhibited tumor growth and invasiveness in vivo by suppressing the expression of Ki-67, STAT3 and phosphor-ERK1/2. The results imply that the anti-IL6R may be a promising targeted drug for CRC.


Assuntos
Anticorpos Monoclonais/farmacologia , Neoplasias Colorretais/prevenção & controle , Neovascularização Patológica/prevenção & controle , Receptores de Interleucina-6/antagonistas & inibidores , Animais , Apoptose , Proliferação de Células , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Receptores de Interleucina-6/imunologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Anticancer Res ; 41(10): 4985-4993, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593446

RESUMO

BACKGROUND/AIM: There is an increasing use of immunotherapy for non-small cell lung cancer (NSCLC) patients. The present study analysed the effect of antibiotic use on the outcome of NSCLC patients undergoing treatment with anti-programmed cell death-1 (anti-PD-1) immunotherapy. PATIENTS AND METHODS: This was a retrospective study of 69 NSCLC patients. Eighteen out of 69 patients received antibiotics within 21 days before or within 21 days after start of anti-PD-1 therapy. RESULTS: Patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to those who did not use antibiotics. Multivariate analysis showed that antibiotic treatment of patients on anti-PD-1 antibody therapy was an independent negative predictive factor of PFS; however, it was not a significant independent predictive factor of OS. CONCLUSION: Use of antibiotics within 21 days before and after anti-PD-1 treatment initiation in patients with NSCLC strongly reduced OS and PFS, suggesting the two treatments should not be combined.


Assuntos
Antibacterianos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Imunoterapia/métodos , Neoplasias Pulmonares/mortalidade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Med Sci Monit ; 27: e934949, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34602605

RESUMO

There have been five viral pandemics in the past century, four were due to influenza, and the ongoing COVID-19 pandemic is due to SARS-CoV-2 infection. During the COVID-19 pandemic, there has been a 99% global reduction in the diagnosis of influenza. Also, from 2020, global mortality rates from influenza fell to record levels during the influenza seasons in the southern and northern hemispheres. However, as social restrictions become lifted and the winter season begins in the northern hemisphere, it is expected that influenza will re-emerge. The World Health Organization (WHO) FluNet surveillance platform provides global surveillance data on influenza, and the US Centers for Disease Control and Prevention (CDC) records national weekly infection rates. Both surveillance programs have identified zoonotic avian and swine influenza variants in humans. The WHO Pandemic Influenza Preparedness (PIP) Framework requires WHO Member States to share data on cases of emerging influenza viruses with pandemic potential in a regular and timely way. The WHO PIP Framework organizes the Global Influenza Surveillance and Response System (GISRS), a global network of public health laboratories developing candidate virus vaccines. This Editorial aims to present the reasons for concern regarding the emergence of pandemic influenza viruses driven by the social and public health responses to the COVID-19 pandemic and highlights the importance of global influenza surveillance at this time.


Assuntos
COVID-19/epidemiologia , Influenza Humana/epidemiologia , Orthomyxoviridae/imunologia , Pandemias , COVID-19/imunologia , Humanos , Influenza Humana/imunologia , SARS-CoV-2
10.
Sovrem Tekhnologii Med ; 13(3): 81-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603758

RESUMO

The pandemic of the new coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread all over the world. The large amount of information that appears every day requires comprehension and systematization. The immunological aspects of the virus-host interaction are the core issues in the effective treatment and prevention of COVID-19' development. The review analyzes the known pathways of the viral invasion and evasion, the mechanisms of the cytokine storm, endothelial damage, and hypercoagulability associated with SARS-CoV-2 infection. Clinical data from previous SARS and MERS epidemics is discussed here. We also address the therapeutic approaches based on the basic knowledge of immune response and the blood cells' immune functions, as well as the ways to reduce their hyperactivation. The use of interferon therapy, anti-inflammatory therapy, anti-cytokine therapy, neutralizing antibodies, convalescent plasma, and mesenchymal stem cells, as well as prophylactic vaccines, is discussed.


Assuntos
COVID-19/tratamento farmacológico , Interações Hospedeiro-Patógeno/imunologia , Pandemias , SARS-CoV-2/fisiologia , COVID-19/epidemiologia , COVID-19/imunologia , Humanos
11.
Acta Med Indones ; 53(3): 319-325, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34611072

RESUMO

One of the main causes of death in COVID-19 is the dysregulation of the host's immune system which leads to cytokine storm, a potentially fatal systemic inflammatory syndrome. Interleukin 6 (IL-6) is a pro-inflammatory cytokine that is produced in response to infections and tissue injuries and is believed to play a pivotal role in the event of a cytokine storm, as signified by its increase in the process. Considering the role of IL-6 as a pro-inflammatory cytokine in the process of cytokine storm in COVID-19, perceiving IL-6 as a therapeutic target could prove to be promising. Tocilizumab is a monoclonal antibody that competitively inhibits the binding of IL-6 to its receptor (IL-6R). The use of IL-6R blocker is recommended for severe COVID-19 patients in the latest therapeutic guideline published by the World Health Organization (WHO), but the timing of the administration has not been specified. While previous studies about the use of tocilizumab in COVID-19 patients have shown various results, these studies do not emphasize on plasma IL-6 levels when deciding the time of tocilizumab administration. In this case series, we present three patients with moderate to severe COVID-19 infections that receive tocilizumab as an adjunct to the standard of care therapy. This case series introduces the novel idea that the timely use of tocilizumab as signified by plasma IL-6 levels in moderate to severe COVID-19 patients could potentially improve overall clinical condition and increase survival rate.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Síndrome da Liberação de Citocina , Interleucina-6 , Receptores de Interleucina-6/imunologia , Tempo para o Tratamento , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Monitoramento de Medicamentos/métodos , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Front Endocrinol (Lausanne) ; 12: 705214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594302

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health crisis affecting millions of people worldwide. SARS-CoV-2 enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2) after being cleaved by the transmembrane protease serine 2 (TMPRSS2). In addition to the lung, gastrointestinal tract and kidney, ACE2 is also extensively expressed in endocrine tissues, including the pituitary and adrenal glands. Although glucocorticoids could play a central role as immunosuppressants during the cytokine storm, they can have both stimulating and inhibitory effects on immune response, depending on the timing of their administration and their circulating levels. Patients with adrenal insufficiency (AI) or Cushing's syndrome (CS) are therefore vulnerable groups in relation to COVID-19. Additionally, patients with adrenocortical carcinoma (ACC) could also be more vulnerable to COVID-19 due to the immunosuppressive state caused by the cancer itself, by secreted glucocorticoids, and by anticancer treatments. This review comprehensively summarizes the current literature on susceptibility to and outcome of COVID-19 in AI, CS and ACC patients and emphasizes potential pathophysiological mechanisms of susceptibility to COVID-19 as well as the management of these patients in case of SARS-CoV-2. Finally, by performing an in silico analysis, we describe the mRNA expression of ACE2, TMPRSS2 and the genes encoding their co-receptors CTSB, CTSL and FURIN in normal adrenal and adrenocortical tumors (both adenomas and carcinomas).


Assuntos
COVID-19/complicações , COVID-19/virologia , Glucocorticoides/administração & dosagem , Insuficiência Adrenal/complicações , Insuficiência Adrenal/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , COVID-19/genética , COVID-19/imunologia , Síndrome de Cushing/complicações , Síndrome de Cushing/imunologia , Humanos , Neoplasias/complicações , Neoplasias/imunologia , SARS-CoV-2/genética , SARS-CoV-2/fisiologia
13.
Nat Methods ; 18(10): 1181-1191, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594031

RESUMO

Cytokines are critical for intercellular communication in human health and disease, but the investigation of cytokine signaling activity has remained challenging due to the short half-lives of cytokines and the complexity/redundancy of cytokine functions. To address these challenges, we developed the Cytokine Signaling Analyzer (CytoSig; https://cytosig.ccr.cancer.gov/ ), providing both a database of target genes modulated by cytokines and a predictive model of cytokine signaling cascades from transcriptomic profiles. We collected 20,591 transcriptome profiles for human cytokine, chemokine and growth factor responses. This atlas of transcriptional patterns induced by cytokines enabled the reliable prediction of signaling activities in distinct cell populations in infectious diseases, chronic inflammation and cancer using bulk and single-cell transcriptomic data. CytoSig revealed previously unidentified roles of many cytokines, such as BMP6 as an anti-inflammatory factor, and identified candidate therapeutic targets in human inflammatory diseases, such as CXCL8 for severe coronavirus disease 2019.


Assuntos
COVID-19/imunologia , Citocinas/metabolismo , Bases de Dados de Proteínas , SARS-CoV-2 , COVID-19/metabolismo , Citocinas/genética , Regulação da Expressão Gênica/imunologia , Regulação da Expressão Gênica/fisiologia , Humanos , Transdução de Sinais/fisiologia
14.
PLoS One ; 16(10): e0257646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34610031

RESUMO

Dialysis patients are both the most likely to benefit from vaccine protection against SARS-CoV-2 and at the highest risk of not developing an immune response. Data from the medical field are thus mandatory. We report our experience with a BNT162b2-mRNA vaccine in a retrospective analysis of 241 dialysis patients including 193 who underwent anti-Spike-Protein-Receptor-Binding-Domain (RBD) IgG analysis. We show that a pro-active vaccine campaign is effective in convincing most patients to be vaccinated (95%) and frequently elicits a specific antibody response (94.3% after two doses and 98.4% after three doses). Only immunocompromised Status is associated with lack of seroconversion (OR 7.6 [1.5-38.2], p = 0.02). We also identify factors associated with low response (last quartile; IgG<500AU/mL): immunocompromised status, age, absence of RAAS inhibitors, low lymphocytes count, high C Reactive Protein; and with high response (high quartile; IgG>7000AU/mL): age; previous SARS-CoV-2 infection and active Cancer. From this experience, we propose a strategy integrating anti-spike IgG monitoring to guide revaccination and dialysis center management in pandemic times.


Assuntos
Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Imunidade Humoral , Insuficiência Renal Crônica/patologia , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Proteína C-Reativa/análise , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação
15.
Int J Immunopathol Pharmacol ; 35: 20587384211048567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34619994

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) had become a worldwide health threat. Early prediction of the severity of COVID-19 patients was important for reducing death rate and controlling this disease. METHODS AND MATERIALS: A total of 301 patients confirmed with COVID-19 in Wuhan from 8 February to 10 April 2020 were included. Clinical data were collected and analyzed. Diagnostic and prognostic utility of blood cell counts and lymphocyte subsets in COVID-19 patients were investigated. The receiver operator characteristic curve (ROC) was used in discriminating the mild and severe/critical cases. RESULTS: There were difference in blood cell counts and lymphocyte subsets among mild, severe and critical patients, which were also influenced by comorbidities and duration of disease. The area under the ROC of lymphocyte, CD3+ T cells, CD4+ T cells, and CD8+ T cells were 0.718, 0.721, 0.718, and 0.670, which were higher than that of other hematological parameters. The optimal threshold was 1205, 691, 402, and 177 per µl, respectively. Patients with higher counts of lymphocyte, CD3+ T cells, CD4+ T cells, or CD8+ T cells were correlated with shorter length of stay in hospital (p < 0.05). Multivariable Cox regression analysis showed disease severity, CD3+ T cells counts and time when the nucleic acid turned negative were independent risk factors for in-hospital death of COVID-19 patients (p < 0.05). CONCLUSION: Blood cell counts and lymphocyte subsets correlated with severity of COVID-19.


Assuntos
COVID-19/imunologia , Subpopulações de Linfócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/virologia , China , Feminino , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Subpopulações de Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
16.
Anticancer Res ; 41(10): 4741-4751, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593423

RESUMO

BACKGROUND/AIM: Heat shock protein 105 (HSP105) is overexpressed in various cancers, but not in normal tissues. We investigated the expression levels of HSP105 in cervical cancer and the efficacy of immunotherapy targeting HSP105. MATERIALS AND METHODS: Previously, we established human leukocyte antigen-A*02:01 (HLA-A2) restricted HSP105 peptide-specific cytotoxic T lymphocyte (CTL) clones from a colorectal cancer patient vaccinated with an HSP105 peptide. Herein, we evaluated the expression of HSP105 in cervical cancer and cervical intraepithelial neoplasia. Moreover, we tested the effectiveness of an HLA-A2-restricted HSP105 peptide-specific CTL clone against cervical cancer cell lines. RESULTS: HSP105 was expressed in 95% (19/20) of examined cervical cancer tissues. Moreover, the HSP105 peptide-specific CTL clone recognized HSP105- and HLA-A*02:01-positive cervical cancer cell lines and also showed that cytotoxicity against the cervical cancer cell lines depends on HSP105 peptide and HLA class I restricted manners. CONCLUSION: HSP105 could be an effective target for immunotherapy in patients with cervical cancer.


Assuntos
Proteínas de Choque Térmico HSP110/imunologia , Imunoterapia/métodos , Neoplasias do Colo do Útero/terapia , Animais , Linhagem Celular Tumoral , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Proteínas de Choque Térmico HSP110/metabolismo , Humanos , Camundongos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/transplante , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Anticancer Res ; 41(10): 4761-4769, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593425

RESUMO

BACKGROUND/AIM: The early stage of atherosclerosis (AS) demonstrates a lipid-driven inflammatory cytokine increase. In the present study, we aimed to use ultrasound-targeted microbubble delivery (UTMD) therapy with the Endostar-loaded target microbubbles (MBs) to reduce AS-related inflammatory response. MATERIALS AND METHODS: Normal and lipopolysaccharide (LPS) induced human umbilical vein endothelial cells (HUVECs) were placed in a parallel-plate flow chamber. MBs were perfused through the parallel-plate flow chamber to mimic physiological blood flow. Five groups were set up: G1: Negative control (normal HUVECs); G2: LPS control (LPS induced HUVECs); G3: ICAM-1-loaded-MBs (MBi); G4: Endostar-loaded-MBs (MBe) and G5: Endostar-ICAM-1-loaded-MBs (MBei). mRNA expression of inflammatory factors and release of inflammatory cytokines were detected by RT-PCR and ELISA, respectively. RESULTS: After treatment with MBei, the mRNA expression of cell adhesion molecule-1 (CD31) (p=0.004), endothelin-1 (ET-1) (p=0.010), von willebrand factor (vWF) (p=0.018), extracellular regulated protein kinases (ERK) (p=0.046) and nuclear factor kappa B (NF-κB) (p=0.003) were significantly reduced compared to LPS-induced HUVECs. Release of inflammatory cytokines including tissue factor (TF) (p=0.033), tissue factor pathway inhibitor (TF-PI) (p=0.019), ET-1 (p=0.014), vWF (p=0.030) and blood-coagulation factor VIIα (FVIIα) (p=0.000) were also significantly reduced compared to LPS-induced HUVECs. CONCLUSION: UTMD therapy can inhibit the inflammatory response by reducing atherosclerotic-related inflammatory factors, suggesting a potential treatment at the early-stage of AS.


Assuntos
Anti-Inflamatórios/farmacologia , Fibrinolíticos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Microbolhas , Anti-Inflamatórios/química , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/terapia , Adesão Celular , Endostatinas/química , Endostatinas/farmacologia , Fibrinolíticos/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Ultrassom
18.
Anticancer Res ; 41(10): 4837-4855, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593432

RESUMO

BACKGROUND/AIM: The adenovirus vector- carrying reduced expression in immortalized cell (REIC) gene (Ad-REIC) increases endoplasmic reticulum stress chaperone GRP78/BiP expression and induces the JNK-mediated apoptotic pathway. We aimed to determine whether Ad-REIC-induced apoptotic cell death can trigger immunogenic cell death (ICD). MATERIALS AND METHODS: We examined the emission of damage-associated molecular patterns in vitro and the vaccination effect in vivo. We determined the immunological changes in the tumour microenvironment by putative ICD inducers and the combined effects of immune checkpoint blockade therapies. RESULTS: Ad-REIC induced the release of high-mobility group box 1 and adenosine triphosphate and the translocation of calreticulin in murine mesothelioma AB12 cells. The vaccination effect was elicited by Ad-REIC treatment in vivo. The effect of Ad-REIC was potentiated by anti-cytotoxic T-lymphocyte-associated protein 4 antibody treatment in a murine mesothelioma AB1-HA cell model. CONCLUSION: Ad-REIC induces ICD in malignant mesothelioma.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Morte Celular Imunogênica/efeitos dos fármacos , Mesotelioma Maligno/terapia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Trifosfato de Adenosina/metabolismo , Adenoviridae/genética , Animais , Apoptose/efeitos dos fármacos , Antígenos CD8/metabolismo , Calreticulina/metabolismo , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Terapia Combinada , Terapia Genética , Vetores Genéticos , Proteína HMGB1/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Mesotelioma Maligno/imunologia , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Anticancer Res ; 41(10): 4857-4865, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593433

RESUMO

BACKGROUND/AIM: M1 macrophages have antitumour effects, while M2 macrophages promote tumour proliferation and invasion. The clinical significance of the M2-specific marker CD204 has not been elucidated in colorectal cancer (CRC). We investigated the prognostic significance of CD204- and CD68-positivity in specimens from patients with CRC and examined the effects of M2 polarized-macrophages on the proliferative and invasive potentials of CRC cell lines in vitro. MATERIALS AND METHODS: Surgical tumour specimens from 206 patients with Stage II and III CRC were examined by immunohistochemistry. Proliferation and invasion assays and flow cytometry were used to investigate CD204 expression in macrophages co-cultured with three CRC cell lines. RESULTS: Infiltration of CD204-positive cells was significantly associated with shorter overall survival and relapse-free survival; no association was observed for CD68. M2-polarized macrophages significantly promoted proliferation and invasion of CRC cells. CONCLUSION: Higher infiltration of CD204-positive macrophages into the tumour-microenvironment might be prognostically important in CRC.


Assuntos
Neoplasias Colorretais/patologia , Receptores Depuradores Classe A/imunologia , Macrófagos Associados a Tumor/imunologia , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Ativação de Macrófagos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Microambiente Tumoral/imunologia
20.
Front Immunol ; 12: 739037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594341

RESUMO

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients. Methods: Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients. Results: Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients. Conclusion: Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.


Assuntos
COVID-19/terapia , Convalescença , SARS-CoV-2/imunologia , Soroconversão , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Doadores de Sangue , COVID-19/sangue , COVID-19/imunologia , Feminino , Humanos , Imunização Passiva , Cinética , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , RNA Viral/sangue
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