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1.
Cancer Cell Int ; 23(1): 86, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37158883

RESUMO

Today, cancer treatment is one of the fundamental problems facing clinicians and researchers worldwide. Efforts to find an excellent way to treat this illness continue, and new therapeutic strategies are developed quickly. Adoptive cell therapy (ACT) is a practical approach that has been emerged to improve clinical outcomes in cancer patients. In the ACT, one of the best ways to arm the immune cells against tumors is by employing chimeric antigen receptors (CARs) via genetic engineering. CAR equips cells to target specific antigens on tumor cells and selectively eradicate them. Researchers have achieved promising preclinical and clinical outcomes with different cells by using CARs. One of the potent immune cells that seems to be a good candidate for CAR-immune cell therapy is the Natural Killer-T (NKT) cell. NKT cells have multiple features that make them potent cells against tumors and would be a powerful replacement for T cells and natural killer (NK) cells. NKT cells are cytotoxic immune cells with various capabilities and no notable side effects on normal cells. The current study aimed to comprehensively provide the latest advances in CAR-NKT cell therapy for cancers.

2.
Cancer Cell Int ; 23(1): 162, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568193

RESUMO

Lung cancer continues to be the leading cause of cancer-related death worldwide. In the last decade, significant advancements in the diagnosis and treatment of lung cancer, particularly NSCLC, have been achieved with the help of molecular translational research. Among the hopeful breakthroughs in therapeutic approaches, advances in targeted therapy have brought the most successful outcomes in NSCLC treatment. In targeted therapy, antagonists target the specific genes, proteins, or the microenvironment of tumors supporting cancer growth and survival. Indeed, cancer can be managed by blocking the target genes related to tumor cell progression without causing noticeable damage to normal cells. Currently, efforts have been focused on improving the targeted therapy aspects regarding the encouraging outcomes in cancer treatment and the quality of life of patients. Treatment with targeted therapy for NSCLC is changing rapidly due to the pace of scientific research. Accordingly, this updated study aimed to discuss the tumor target antigens comprehensively and targeted therapy-related agents in NSCLC. The current study also summarized the available clinical trial studies for NSCLC patients.

3.
Inflammopharmacology ; 31(1): 145-169, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36609717

RESUMO

Cell-derived exosomes have opened new horizons in modern therapy for advanced drug delivery and therapeutic applications, due to their key features such as low immunogenicity, high physicochemical stability, capacity to penetrate into tissues, and the innate capacity to communicate with other cells over long distances. Exosome-based liquid biopsy has been potentially used for the diagnosis and prognosis of a range of disorders. Exosomes deliver therapeutic agents, including immunological modulators, therapeutic drugs, and antisense oligonucleotides to certain targets, and can be used as vaccines, though their clinical application is still far from reality. Producing exosomes on a large-scale is restricted to their low circulation lifetime, weak targeting capacity, and inappropriate controls, which need to be refined before being implemented in practice. Several bioengineering methods have been used for refining therapeutic applications of exosomes and promoting their effectiveness, on the one hand, and addressing the existing challenges, on the other. In the short run, new diagnostic platforms and emerging therapeutic strategies will further develop exosome engineering and therapeutic potential. This requires a thorough analysis of exosome engineering approaches along with their merits and drawbacks, as outlined in this paper. The present study is a comprehensive review of novel techniques for exosome development in terms of circulation time in the body, targeting capacity, and higher drug loading/delivery efficacies.


Assuntos
Exossomos , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas
4.
Cancer Cell Int ; 22(1): 365, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36419058

RESUMO

In recent decades, the advent of immune-based therapies, most notably Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. The promising results of numerous studies indicate that CAR-T cell therapy has had a remarkable ability and successful performance in treating blood cancers. However, the heterogeneity and immunosuppressive tumor microenvironment (TME) of solid tumors have challenged the effectiveness of these anti-tumor fighters by creating various barriers. Despite the promising results of this therapeutic approach, including tumor degradation and patient improvement, there are some concerns about the efficacy and safety of the widespread use of this treatment in the clinic. Complex and suppressing tumor microenvironment, tumor antigen heterogeneity, the difficulty of cell trafficking, CAR-T cell exhaustion, and reduced cytotoxicity in the tumor site limit the applicability of CAR-T cell therapy and highlights the requiring to improve the performance of this treatment. With this in mind, in the last decade, many efforts have been made to use other treatments for cancer in combination with tuberculosis to increase the effectiveness of CAR-T cell therapy, especially in solid tumors. The combination therapy results have promising consequences for tumor regression and better cancer control compared to single therapies. Therefore, this study aimed to comprehensively discuss different cancer treatment methods in combination with CAR-T cell therapy and their therapeutic outcomes, which can be a helpful perspective for improving cancer treatment in the near future.

5.
J Cell Physiol ; 236(7): 5325-5338, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33372280

RESUMO

In novel coronavirus disease 2019 (COVID-19), the increased frequency and overactivation of T helper (Th) 17 cells and subsequent production of large amounts of proinflammatory cytokines result in hyperinflammation and disease progression. The current study aimed to investigate the therapeutic effects of nanocurcumin on the frequency and responses of Th17 cells in mild and severe COVID-19 patients. In this study, 40 severe COVID-19 intensive care unit-admitted patients and 40 patients in mild condition were included. The frequency of Th17 cells, the messenger RNA expression of Th17 cell-related factors (RAR-related orphan receptor γt, interleukin [IL]-17, IL-21, IL-23, and granulocyte-macrophage colony-stimulating factor), and the serum levels of cytokines were measured in both nanocurcumin and placebo-treated groups before and after treatment. A significant decrease in the number of Th17 cells, downregulation of Th17 cell-related factors, and decreased levels of Th17 cell-related cytokines were found in mild and severe COVID-19 patients treated by nanocurcumin compared to the placebo group. Moreover, the abovementioned parameters were significantly decreased in the nanocurcumin-treated group after treatment versus before treatment. Curcumin could reduce the frequency of Th17 cells and their related inflammatory factors in both mild and severe COVID-19 patients. Hence, it could be considered as a potential modulatory compound in improving the patient's inflammatory condition.


Assuntos
Tratamento Farmacológico da COVID-19 , Curcumina/uso terapêutico , Imunomodulação/efeitos dos fármacos , Nanopartículas/uso terapêutico , Células Th17/efeitos dos fármacos , Adulto , Citocinas/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , SARS-CoV-2/efeitos dos fármacos , Índice de Gravidade de Doença , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/virologia , Células Th17/metabolismo
6.
J Cell Physiol ; 236(4): 2829-2839, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32926425

RESUMO

In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-ß [TGF-ß], and IL-10), and cytokine secretion levels (TGF-ß and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.


Assuntos
COVID-19/imunologia , Inflamação/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Idoso , Citocinas/imunologia , Feminino , Humanos , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia
7.
J Cell Biochem ; 122(10): 1389-1412, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34160093

RESUMO

The emergence of a new acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the cause of the 2019-nCOV disease (COVID-19), has caused a pandemic and a global health crisis. Rapid human-to-human transmission, even from asymptomatic individuals, has led to the quick spread of the virus worldwide, causing a wide range of clinical manifestations from cold-like symptoms to severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan injury, and even death. Therefore, using rapid and accurate diagnostic methods to identify the virus and subsequently select appropriate and effective treatments can help improvement of patients and control the pandemic. So far, various treatment regimens along with prophylactic vaccines have been developed to manage COVID-19-infected patients. Among these, antibody-based therapies, including neutralizing antibodies (against different parts of the virus), polyclonal and monoclonal antibodies, plasma therapy, and high-dose intravenous immunoglobulin (IVIG) have shown promising outcomes in accelerating and improving the treatment process of patients, avoiding the viral spreading widely, and managing the pandemic. In the current review paper, different types and applications of therapeutic antibodies in the COVID-19 treatment are comprehensively discussed.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia , Pandemias , SARS-CoV-2 , Humanos
8.
Cytokine ; 146: 155626, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34157522

RESUMO

BACKGROUND: Ischemic stroke is caused by a sudden neurological defect following a vascular occlusion and elicits a local and systemic inflammation in brain tissue. Interleukin-38 is an anti-inflammatory cytokine associated with ischemic and inflammatory diseases. This study was designed to analyze the effect of tPA therapy on interleukin-38 serum level changes and the serum level of IL-38 in the prognosis of ischemic stroke patients in the next three months. METHODS: We enrolled 29 ischemic stroke patients confirmed by a neurologist based on radiologic and clinical manifestation between 2019 September to 2020 February. The patients who had NIHSS more than 6 with no underlying inflammatory diseases were selected for tPA therapy. On admission and 24 h after tPA therapy, the IL-38 serum level was measured by ELISA kit. RESULTS: The results showed that serum levels of IL-38 were significantly increased after tPA therapy (P < 0.001). A remarkable relationship was observed between the modified Rankin Score (mRS) and IL-38 serum changes in response to tPA therapy (P < 0.001). Besides, IL-38 serum changes following tPA were dramatically related to NIHSS at hospitalization (P = 0.007). Also, our analysis posed a positive relation between NIHSS at hospitalization and mRs criteria (P = 0.023). No notable relation has been observed between IL-38 serum levels before and after tPA and mRs (P = 0.601 and P = 0.074, respectively). Furthermore, there was no evidence for the relation between NIHSS at hospitalization and IL-38 levels before and after tPA (P = 0.457 and P = 0.105, respectively). CONCLUSION: The results indicate that tPA could meaningfully increase the IL-38 serum level. Also, a negative correlation has been found between IL-38 serum changes in response to tPA and mRS. Since the lower changes in IL-38 serum level result in a poorer prognosis, we conclude that IL-38 serum changes might be a novel early predictor factor for ischemic stroke prognosis.


Assuntos
Isquemia Encefálica/sangue , Interleucinas/sangue , AVC Isquêmico/sangue , Idoso , Isquemia Encefálica/complicações , Feminino , Humanos , AVC Isquêmico/complicações , Masculino , Prognóstico , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/complicações
9.
Cell Biol Int ; 45(7): 1498-1509, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33724614

RESUMO

Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing-remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell-related factors (FoxP3, IL-10, TGF-ß, miR-17, miR-27, and miR-146A), and the secretion levels of IL-10 and TGF-ß were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR-17 and miR-27), IL-10, and TGF-ß factors in patients after oxygen-ozone (O2 -O3 ) therapy compared to before treatment. In contrast, oxygen-ozone therapy notably decreased the expression level of miR-146a in treated patients. Interestingly, the secretion levels of both IL-10 and TGF-ß cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen-ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen-ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.


Assuntos
Esclerose Múltipla/terapia , Oxigênio/farmacologia , Ozônio/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/patologia , Adulto Jovem
10.
Adv Exp Med Biol ; 1318: 449-468, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33973194

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel zoonotic virus identified as the cause of coronavirus disease 2019 (COVID-19) that has crossed species and infected humans. In order to develop new insights on the immune-based treatments against this disease, it is vital to understand the immunopathology of the COVID-19, implications of the immune response to SARS-CoV-2, and immune dysfunction in response to SARS-CoV-2. There is no approved drug for the treatment of COVID-19. It is, thus, promising to design immune-based treatments that inhibit the infectious mechanism of the virus, improve the inadequate immune response, or regulate the hyperactivated immune response in severely ill patients. According to the antiviral immune response against the virus, antibody-based immunotherapies of COVID-19 include injection of convalescent plasma from recovered patients, high-dose intravenous immunoglobulins (IVIG), monoclonal antibodies, and polyclonal antibodies. Also, cell-based treatment, vaccine-based approaches, cytokine-based immunotherapy, immune checkpoint inhibitors, JAK inhibitors, decoy receptors, and immunosuppressive drugs are discussed in this chapter.


Assuntos
COVID-19 , Infecções por Coronavirus , Antivirais/uso terapêutico , COVID-19/terapia , Infecções por Coronavirus/tratamento farmacológico , Humanos , Imunização Passiva , SARS-CoV-2 , Soroterapia para COVID-19
11.
Immunopharmacol Immunotoxicol ; 43(5): 562-570, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314306

RESUMO

BACKGROUND: Nonalcoholic Steatohepatitis (NASH) results from the accumulation of fatty acids in the liver. The elevated production of pro-inflammatory factors is the reason for the hyper inflammation in NASH. The α-L-Guluronic acid (G2013), a new member of NSAID family, is a plant-originated agent with immunomodulatory properties. The current study investigated the effects of G2013 on inflammatory factors in PBMCs of NASH patients. METHODS: PBMCs of 14 NASH patients and 14 healthy controls were isolated and cultured. The patient's cells were treated with low (5 µg/mL) and moderate (25 µg/mL) doses of G2013 alongside the diclofenac optimum dose (3 µg/mL). The expression and secretion levels of variables were assessed by real-time PCR and ELISA, respectively. RESULTS: Findings indicated that the expression levels of TLR4 and NF-κB, as well as the secretion levels of TNF-α and IL-6 cytokines, were significantly elevated in NASH patients compared to healthy individuals. The expression levels of TLR4 and NF-κB were strikingly downregulated in treated cells of patients in both low and moderate doses of G2013. A considerable reduction was obtained in the secretion level of IL-6 using both low and moderate doses of G2013 and in the secretion level of TNF-α using the moderate dose of G2013. CONCLUSION: The results indicated that G2013 could meaningfully decrease the expression and secretion levels of evaluated factors (TLR4, NF-κB, TNF-α, and IL-6) in PMBCs of NASH cases. Since there is no effective treatment for NASH patients, we hope that G2013 would be a promising immunomodulatory agent in reducing inflammation and improvement of patients.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Hexurônicos/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Células Cultivadas , Feminino , Ácidos Hexurônicos/uso terapêutico , Humanos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Técnicas In Vitro , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/imunologia , Adulto Jovem
12.
J Cell Physiol ; 235(12): 9211-9229, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32452050

RESUMO

At the end of December 2019, a novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) appeared as the third unheard of outbreak of human coronavirus infection in the 21st century. First, in Wuhan, China, the novel SARS-CoV2 was named by the World Health Organization (WHO), as 2019-nCOV (COVID-19), and spread extremely all over the world. SARS-CoV2 is transmitted to individuals by human-to-human transmission leading to severe viral pneumonia and respiratory system injury. SARS-CoV2 elicits infections from the common cold to severe conditions accompanied by lung injury, acute respiratory distress syndrome, and other organ destruction. There is a possibility of virus transmission from asymptomatic cases as active carriers, in addition to symptomatic ones, which is a crucial crisis of COVID-19 that should be considered. Hence, paying more attention to the accurate and immediate diagnosis of suspected and infected cases can be a great help in preventing the rapid spread of the virus, improving the disease prognosis, and controlling the pandemic. In this review, we provide a comprehensive and up-to-date overview of the different types of Clinical and Para-clinical diagnostic methods and their practical features, which can help understand better the applications and capacities of various diagnostic approaches for COVID-19 infected cases.


Assuntos
Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , COVID-19 , Teste para COVID-19 , China/epidemiologia , Coronavirus/efeitos dos fármacos , Coronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , SARS-CoV-2
13.
Life Sci ; 351: 122842, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879158

RESUMO

The aging process has been one of the most necessary research fields in the current century, and knowing different theories of aging and the role of different genetic, epigenetic, molecular, and environmental modulating factors in increasing the knowledge of aging mechanisms and developing appropriate diagnostic, therapeutic, and preventive ways would be helpful. One of the most conserved signs of aging is epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, noncoding RNAs, and extracellular RNAs. Numerous biological processes and hallmarks are vital in aging development, but epigenomic alterations are especially notable because of their importance in gene regulation and cellular identity. The mounting evidence points to a possible interaction between age-related epigenomic alterations and other aging hallmarks, like genome instability. To extend a healthy lifespan and possibly reverse some facets of aging and aging-related diseases, it will be crucial to comprehend global and locus-specific epigenomic modifications and recognize corresponding regulators of health and longevity. In the current study, we will aim to discuss the role of epigenomic mechanisms in aging and the most recent developments in epigenetic diagnostic biomarkers, which have the potential to focus efforts on reversing the destructive signs of aging and extending the lifespan.


Assuntos
Envelhecimento , Biomarcadores , Epigênese Genética , Longevidade , Humanos , Longevidade/genética , Envelhecimento/genética , Animais , Biomarcadores/metabolismo , Metilação de DNA , Epigenômica/métodos
14.
Geroscience ; 46(3): 2933-2950, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409646

RESUMO

Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.


Assuntos
Curcumina , Humanos , Curcumina/farmacologia , Longevidade , Envelhecimento , Suplementos Nutricionais
15.
Life Sci ; 312: 121206, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36403645

RESUMO

Acute inflammatory diseases such as acute colitis, kidney injury, liver failure, lung injury, myocardial infarction, pancreatitis, septic shock, and spinal cord injury are significant causes of death worldwide. Despite advances in the understanding of its pathophysiology, there are many restrictions in the treatment of these diseases, and new therapeutic approaches are required. Mesenchymal stem cell-based therapy due to immunomodulatory and regenerative properties is a promising candidate for acute inflammatory disease management. Based on preclinical results, mesenchymal stem cells and their-derived secretome improved immunological and clinical parameters. Furthermore, many clinical trials of acute kidney, liver, lung, myocardial, and spinal cord injury have yielded promising results. In this review, we try to provide a comprehensive view of mesenchymal stem cell-based therapy in acute inflammatory diseases as a new treatment approach.


Assuntos
Lesão Pulmonar Aguda , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Lesão Pulmonar Aguda/terapia , Inflamação/terapia
16.
Med Oncol ; 40(5): 155, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37083979

RESUMO

Nowadays, one of the main challenges clinicians face is malignancies. Through the progression of technology in recent years, tumor nature and tumor microenvironment (TME) can be better understood. Because of immune system involvement in tumorigenesis and immune cell dysfunction in the tumor microenvironment, clinicians encounter significant challenges in patient treatment and normal function recovery. The tumor microenvironment can stop the development of tumor antigen-specific helper and cytotoxic T cells in the tumor invasion process. Tumors stimulate the production of proinflammatory and immunosuppressive factors and cells that inhibit immune responses. Despite the more successful outcomes, the current cancer therapeutic approaches, including surgery, chemotherapy, and radiotherapy, have not been effective enough for tumor eradication. Hence, developing new treatment strategies such as monoclonal antibodies, adaptive cell therapies, cancer vaccines, checkpoint inhibitors, and cytokines helps improve cancer treatment. Among adoptive cell therapies, the interaction between the immune system and malignancies and using molecular biology led to the development of chimeric antigen receptor (CAR) T cell therapy. CAR-modified immune cells are one of the modern cancer therapeutic methods with encouraging outcomes in most hematological and solid cancers. The current study aimed to discuss the structure, formation, subtypes, and application of CAR immune cells in hematologic malignancies and solid tumors.


Assuntos
Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Imunoterapia Adotiva/métodos , Linfócitos T Citotóxicos , Antígenos de Neoplasias , Microambiente Tumoral
17.
Transpl Immunol ; 79: 101858, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37236514

RESUMO

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Vacinas contra COVID-19/uso terapêutico , Metotrexato/uso terapêutico , Agentes de Imunomodulação , Imunoglobulina G , Anticorpos Antivirais , Imunidade Celular
18.
Int J Rheum Dis ; 26(7): 1227-1234, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37309305

RESUMO

COVID-19 vaccines approved by the Food and Drug Administration have been studied mainly in healthy individuals and there is limited information on their immunogenicity in patients with autoimmune diseases. Therefore, the current systematic review and meta-analysis study, aimed to comprehensively investigate the immunogenicity of these vaccines in patients with autoimmune inflammatory rheumatoid diseases (AIRDs). A comprehensive literature search was performed on various databases, including Google Scholar, PubMed, Web of Science, EMBASE, and Cochrane Library, to select cohort and randomized clinical trial (RCT) studies up to January 2022. Also, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist protocol and the I2 statistic were used for quality assessment and heterogeneity tests of the selected studies. Fixed and random-effects models were estimated based on the heterogeneity tests, and pooled data were determined as the ratio of mean (ROM) with a 95% confidence interval (CI). As a result, we found that vaccines can cause favorable immunogenicity and antibody response in vaccinated AIRD patients; however, older age and the concomitant consumption of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs) could significantly reduce the vaccine immunogenicity. Consequently, our findings revealed significant humoral responses (seropositive) in AIRD patients following the administration of COVID-19 vaccines.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Autoimunes , Vacinas contra COVID-19 , COVID-19 , Doenças Reumáticas , Adulto , Humanos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico
19.
Regen Med ; 17(6): 401-418, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35545963

RESUMO

Severe traumatic wounds and burns have a high chance of mortality and can leave survivors with many functional disabilities and cosmetic problems, including scars. The healing process requires a harmonious interplay of various cells and growth factors. Different structures of the skin house numerous cells, matrix components and growth factors. Any disturbance in the balance between these components can impair the healing process. The function of cells and growth factors can be manipulated and facilitated to aid tissue repair. In the current review, the authors focus on the importance of the skin microenvironment, the pathophysiology of various types of burns, mechanisms and factors involved in skin repair and wound healing and regeneration of the skin using tissue engineering approaches.


Wounds and ulcers, especially burn wounds, are major causes of morbidity and mortality and pose a significant burden for individuals and societies. The skin has numerous structures that play important roles in wound healing via cells and growth factors. Tissue engineering and regenerative medicine represent a rather new field that focuses on manipulating cells and growth factors, aiming to facilitate repair and regeneration of injured tissues and organs. This review focuses on different burn injuries that can result in nonhealing wounds, provides an overview of several cells and growth factors that are involved in the healing process of the skin and introduces various strategies practiced in tissue engineering with regard to cutaneous wound healing.


Assuntos
Fatores Biológicos , Queimaduras , Engenharia Tecidual , Cicatrização , Fatores Biológicos/metabolismo , Fatores Biológicos/farmacologia , Queimaduras/fisiopatologia , Queimaduras/terapia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Pele/lesões , Pele/metabolismo , Transplante de Pele , Cicatrização/fisiologia
20.
Life Sci ; 310: 120938, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150466

RESUMO

BACKGROUND: Sepsis is a debilitating systemic inflammation that resulted from infection or injury. Despite many advances in treatment, the resulting mortality rate has remained high due to increasing antibiotic resistance and aging communities. The present study investigated the effects of stem cell-derived exosomes in a mouse model of LPS-induced systemic inflammation. MATERIALS AND METHODS: To induce sepsis, the LPS model was used. Mice were divided into three groups: normal, patient group (LPS + PBS), and treatment group (LPS + exosome). The treatment group received an intravenous exosome 1 h after induction of the model. Patient and treatment groups were sacrificed at 4, 6, 24, and 48 h after induction of the model, and their tissues were isolated. Blood samples were taken from animal hearts to perform biochemical and immunological tests. The study results were analyzed using Graph Pad Prism software version 9. RESULTS: Mesenchymal stem cell-derived exosomes decreased serum levels of ALT and AST liver enzymes, decreased neutrophil to lymphocyte ratio (NLR), and improved kidney, liver, and lung tissue damage at 4, 6, and 24 h after model induction. At 24 h, the exosomes were able to reduce serum urea levels. This study revealed decreased levels of inflammatory cytokines such as IL-6, IL-1ß, and TNF-α after exosome injection. CONCLUSION: Our findings suggest that treating mice with stem cell-derived exosomes can ameliorate the destructive effects of inflammation caused by sepsis by reducing inflammatory factors and tissue damage.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Sepse , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Inflamação , Modelos Animais de Doenças , Sepse/induzido quimicamente , Sepse/terapia
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