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1.
Stem Cell Res Ther ; 12(1): 465, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34412685

RESUMO

Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.


Assuntos
Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia , Imunoterapia Adotiva , Leucemia Mieloide Aguda/terapia , Receptores de Antígenos Quiméricos/genética , Linfócitos T
2.
Eur J Pharmacol ; 909: 174419, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391770

RESUMO

Today, herbal-derived compounds are being increasingly studied in cancer treatment. Over the past decade, Arctigenin has been introduced as a bioactive dibenzylbutyrolactone lignan which is found in Chinese herbal medicines. In addition to anti-microbial, anti-inflammatory, immune-modulatory functions, Arctigenin has attracted growing attention due to its anti-tumor capabilities. It has been shown that Arctigenin can induce apoptosis and necrosis and abolish drug resistance in tumor cells by inducing apoptotic signaling pathways, caspases, cell cycle arrest, and the modulating proteasome. Moreover, Arctigenin mediates other anti-tumor functions through several mechanisms. It has been demonstrated that Arctigenin can act as an anti-inflammatory compound to inhibit inflammation in the tumor microenvironment. It also downregulates factors involved in tumor metastasis and angiogenesis, such as matrix metalloproteinases, N-cadherin, TGF-ß, and VEGF. Additionally, Arctigenin, through modulation of MAPK signaling pathways and stress-related proteins, is able to abolish tumor cell growth in nutrient-deprived conditions. Due to the limited solubility of Arctigenin in water, it is suggested that modification of this compound through amino acid esterification can improve its pharmacogenetic properties. Collectively, it is hoped that using Arctigenin or its derivates might introduce new chemotherapeutic approaches in future treatment.

3.
DNA Repair (Amst) ; 107: 103203, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34390915

RESUMO

Hematologic malignancies include various diseases that develop from hematopoietic stem cells of bone marrow or lymphatic organs. Currently, conventional DNA-damage-based chemotherapy drugs are approved as standard therapeutic regimens for these malignancies. Although many improvements have been made, patients with relapsed or refractory hematological malignancies have a poor prognosis. Therefore, novel and practical therapeutic approaches are required for the treatment of these diseases. Interestingly several studies have shown that targeting Wee1 kinase in the Hematological malignancies, including AML, ALL, CML, CLL, DLBCL, BL, MCL, etc., can be an effective therapeutic strategy. It plays an essential role in regulating the cell cycle process by abrogating the G2-M cell-cycle checkpoint, which provides time for DNA damage repair before mitotic entry. Consistently, Wee1 overexpression is observed in various Hematological malignancies. Also, in healthy normal cells, repairing DNA damages occurs due to G1-S checkpoint function; however, in the cancer cells, which have an impaired G1-S checkpoint, the damaged DNA repair process depends on the G2-M checkpoint function. Thus, Wee1 inhibition could be a promising target in the presence of DNA damage in order to potentiate multiple therapeutic drugs. This review summarized the potentials and challenges of Wee1 inhibition combined with other therapies as a novel effective therapeutic strategy in Hematological malignancies.

4.
Front Immunol ; 12: 681984, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248965

RESUMO

Non-Hodgkin's lymphoma (NHL) is a cancer that starts in the lymphatic system. In NHL, the important part of the immune system, a type of white blood cells called lymphocytes become cancerous. NHL subtypes include marginal zone lymphoma, small lymphocytic lymphoma, follicular lymphoma (FL), and lymphoplasmacytic lymphoma. The disease can emerge in either aggressive or indolent form. 5-year survival duration after diagnosis is poor among patients with aggressive/relapsing form of NHL. Therefore, it is necessary to understand the molecular mechanisms of pathogenesis involved in NHL establishment and progression. In the next step, we can develop innovative therapies for NHL based on our knowledge in signaling pathways, surface antigens, and tumor milieu of NHL. In the recent few decades, several treatment solutions of NHL mainly based on targeted/directed therapies have been evaluated. These approaches include B-cell receptor (BCR) signaling inhibitors, immunomodulatory agents, monoclonal antibodies (mAbs), epigenetic modulators, Bcl-2 inhibitors, checkpoint inhibitors, and T-cell therapy. In recent years, methods based on T cell immunotherapy have been considered as a novel promising anti-cancer strategy in the treatment of various types of cancers, and particularly in blood cancers. These methods could significantly increase the capacity of the immune system to induce durable anti-cancer responses in patients with chemotherapy-resistant lymphoma. One of the promising therapy methods involved in the triumph of immunotherapy is the chimeric antigen receptor (CAR) T cells with dramatically improved killing activity against tumor cells. The CAR-T cell-based anti-cancer therapy targeting a pan-B-cell marker, CD19 is recently approved by the US Food and Drug Administration (FDA) for the treatment of chemotherapy-resistant B-cell NHL. In this review, we will discuss the structure, molecular mechanisms, results of clinical trials, and the toxicity of CAR-T cell-based therapies. Also, we will criticize the clinical aspects, the treatment considerations, and the challenges and possible drawbacks of the application of CAR-T cells in the treatment of NHL.

5.
Hum Immunol ; 82(10): 733-745, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34229864

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is associated with excessive inflammation, as a main reason for severe condition and death. Increased inflammatory cytokines and humoral response to SARS-CoV-2 correlate with COVID-19 immunity and pathogenesis. Importantly, the levels of pro-inflammatory cytokines that increase profoundly in systemic circulation appear as part of the clinical pictures of two overlapping conditions, sepsis and the hemophagocytic syndromes. Both conditions can develop lethal inflammatory responses that lead to tissue damage, however, in many patients hemophagocytic lymphohistiocytosis (HLH) can be differentiated from sepsis. This is a key issue because the life-saving aggressive immunosuppressive treatment, required in the HLH therapy, is absent in sepsis guidelines. This paper aims to describe the pathophysiology and clinical relevance of these distinct entities in the course of COVID-19 that resemble sepsis and further highlights two effector arms of the humoral immune response (inflammatory cytokine and immunoglobulin production) during COVID-19 infection.


Assuntos
COVID-19/imunologia , Imunidade Humoral/imunologia , Animais , Citocinas/imunologia , Humanos , Inflamação/imunologia , Linfo-Histiocitose Hemofagocítica/imunologia , SARS-CoV-2/imunologia , Sepse/imunologia
6.
Stem Cell Rev Rep ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34169411

RESUMO

Musculoskeletal disorders (MSDs) are conditions that can affect muscles, bones, and joints. These disorders are very painful and severely limit patients' mobility and are more common in the elderly. MSCs are multipotent stem cells isolated from embryonic (such as the umbilical cord) and mature sources (such as adipose tissue and bone marrow). These cells can differentiate into various cells such as osteoblasts, adipocytes, chondrocytes, NP-like cells, Etc. Due to MSC characteristics such as immunomodulatory properties, ability to migrate to the site of injury, recruitment of cells involved in repair, production of growth factors, and large amount production of extracellular vesicles, these cells have been used in many regenerative-related medicine studies. Also, MSCs produce different types of EVs, such as exosomes, to the extracellular environment. Exosomes reflect MSCs' characteristics and do not have cell therapy-associated problems because they are cell-free. These vesicles carry proteins, nucleic acids, and lipids to the host cell and change their function. This review focuses on MSCs and MSCs exosomes' role in repairing dense connective tissues such as tendons, cartilage, invertebrate disc, bone fracture, and osteoporosis treatment.

7.
Int Immunopharmacol ; 97: 107828, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091116

RESUMO

In various pathological conditions, cellular immunity plays an important role in immune responses. Amongimmunecells, T lymphocytes pdomotecellular and humoralresponses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19diseasepathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS-CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n = 20), ICU hospitalized patients (n = 30), non-ICU hospitalized patients (n = 30), and normal subjects (n = 20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , Adulto , Idoso , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Imunidade Celular , Inflamação/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Adulto Jovem
8.
Cancer Med ; 10(15): 5191-5202, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34128588

RESUMO

Cancer is a leading cause of death which imposes a substantial financial burden. Among the several mechanisms involved in cancer progression, imbalance of immune cell-derived factors such as cytokines and chemokines plays a central role. IL-25, as a member of the IL-17 cytokine subfamily, exerts a paradoxical role in cancer, including tumor supportive and tumor suppressive. Hence, we have tried to clarify the role of IL-25 and its receptor in tumor progression and cancer prognosis. It has been confirmed that IL-25 exerts a tumor-suppressive role through inducing infiltration of eosinophils and B cells into the tumor microenvironment and activating the apoptotic pathways. In contrast, the tumor-supportive function has been implemented by activating inflammatory cascades, promoting cell cycle, and inducing type-2 immune responses. Since IL-25 has been dysregulated in tumor tissues and this dysregulation is involved in cancer development, its examination can be used as a tumor diagnostic and prognostic biomarker. Moreover, IL-25-based therapeutic approaches have shown promising results in cancer inhibition. In cancers in which IL-25 has a tumor-suppressive function, employing IL-25-enhancing approaches, such as Virulizin® and dihydrobenzofuran administration, has potentially inhibited tumor cell growth. On the other hand, in the case of IL-25-dependent tumor progression, using IL-25 blocking methods, including anti-IL-25 antibodies, might be a complementary approach to the other anticancer agent. Collectively, it is hoped, IL-25 might be a promising target in cancer treatment.

9.
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 , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia , Pandemias , SARS-CoV-2 , Humanos
10.
Cancer Sci ; 112(9): 3427-3436, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34050690

RESUMO

Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR-natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti-cancer functions. Importantly, CAR-NK cells can be utilized as universal cell-based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor-associated antigens (TAAs). Indeed, CAR-NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR-NK cell anti-cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the "off-the-shelf" anti-cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR-NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Receptores de Antígenos Quiméricos/imunologia , Animais , Antígenos de Neoplasias/imunologia , Engenharia Genética/métodos , Vetores Genéticos , Humanos , Camundongos , Receptores de Antígenos Quiméricos/genética , Resultado do Tratamento , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Int Immunopharmacol ; 97: 107681, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33932697

RESUMO

Cancer is a leading cause of death worldwide and imposes a substantial financial burden. Therefore, it is essential to develop cost-effective approaches to inhibit tumor growth and development. The imbalance of cytokines and chemokines play an important role among different mechanisms involved in cancer development. One of the strongly conserved chemokines that is constitutively expressed in skin epithelia is the chemokine CXCL14. As a member of the CXC subfamily of chemokines, CXCL14 is responsible for the infiltration of immune cells, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC)-I expression, and cell mobilization. Moreover, dysregulation of CXCL14 in several cancers has been identified by several studies. Depending on the type or origin of the tumor and components of the tumor microenvironment, CXCL14 plays a conflicting role in cancer. Although fibroblast-derived CXCL14 has a tumor-supportive role, epithelial-derived CXCL14 mainly inhibits tumor progression. Hence, this review will elucidate what is known on the mechanisms of CXCL14 and its therapeutic approaches in tumor treatment. CXCL14 is a promising approach for cancer immunotherapy.

12.
Immunol Cell Biol ; 99(8): 814-832, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33988889

RESUMO

The mechanistic/mammalian target of rapamycin (mTOR) is considered to be an atypical protein kinase that plays a critical role in integrating different cellular and environmental inputs in the form of growth factors, nutrients and energy and, subsequently, in regulating different cellular events, including cell metabolism, survival, homeostasis, growth and cellular differentiation. Immunologically, mTOR is a critical regulator of immune function through integrating numerous signals from the immune microenvironment, which coordinates the functions of immune cells and T cell fate decisions. The crucial role of mTOR in immune responses has been lately even more appreciated. MicroRNAs (miRNAs) are endogenous, small, noncoding single-stranded RNAs that act as molecular regulators involved in multiple processes during immune cells development, homeostasis, activation and effector polarization. Several studies have recently indicated that a range of miRNAs are involved in regulating the phosphoinositide 3-kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway by targeting multiple components of this signaling pathway and modulating the expression and function of these targets. Current evidence has revealed the interplay between miRNAs and the mTOR pathway circuits in various immune cell types. The expression of individual miRNA can affect the function of mTOR signaling to determine the cell fate decisions in immune responses through coordinating immune signaling and cell metabolism. Dysregulation of the mTOR pathway/miRNAs crosstalk has been reported in cancers and various immune-related diseases. Thus, expression profiles of dysregulated miRNAs could influence the mTOR pathway, resulting in the promotion of aberrant immunity. This review summarizes the latest information regarding the reciprocal role of the mTOR signaling pathway and miRNAs in orchestrating immune responses.


Assuntos
MicroRNAs , Diferenciação Celular , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
13.
Expert Rev Mol Med ; 23: e4, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33880989

RESUMO

Today, cancer is one of the leading causes of death worldwide. Lately, cytokine and chemokine imbalances have gained attention amongst different involved pathways in cancer development and attracted much consideration in cancer research. CXCL16, as a member of the CXC subgroup of chemokines, has been attributed to be responsible for immune cell infiltration into the tumour microenvironment. The aberrant expression of CXCL16 has been observed in various cancers. This chemokine has been shown to play a conflicting role in tumour development through inducing pro-inflammatory conditions. The infiltration of various immune and non-immune cells such as lymphocytes, cancer-associated fibroblasts and myeloid-derived suppressor cells by CXCL16 into the tumour microenvironment has complicated the tumour fate. Given this diverse role of CXCL16 in cancer, a better understanding of its function might build-up our knowledge about tumour biology. Hence, this study aimed to review the impact of CXCL16 in cancer and explored its therapeutic application. Consideration of these findings might provide opportunities to achieve novel approaches in cancer treatment and its prognosis.

14.
Science ; 372(6542): 630-635, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33858991

RESUMO

Unconventional ferroelectricity exhibited by hafnia-based thin films-robust at nanoscale sizes-presents tremendous opportunities in nanoelectronics. However, the exact nature of polarization switching remains controversial. We investigated a La0.67Sr0.33MnO3/Hf0.5Zr0.5O2 capacitor interfaced with various top electrodes while performing in situ electrical biasing using atomic-resolution microscopy with direct oxygen imaging as well as with synchrotron nanobeam diffraction. When the top electrode is oxygen reactive, we observe reversible oxygen vacancy migration with electrodes as the source and sink of oxygen and the dielectric layer acting as a fast conduit at millisecond time scales. With nonreactive top electrodes and at longer time scales (seconds), the dielectric layer also acts as an oxygen source and sink. Our results show that ferroelectricity in hafnia-based thin films is unmistakably intertwined with oxygen voltammetry.

15.
J Reprod Immunol ; 145: 103317, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33813342

RESUMO

BACKGROUND: Alongside many complications in understanding the etiology of Preeclampsia (PE), several determinants, such as the imbalanced proportion of anti-angiogenic/proangiogenic T-cell subsets, especially CD4+ (Th17/Treg), as well as alterations in the expression profile of related cytokines, miRNAs, and transcription factors might have been implicated in PE pathogenesis. MATERIAL AND METHOD: After sample collection and preparation, CD4+ cells were isolated from PE and non-PE pregnant woman and were cultured. Furthermore, analysis such as flow cytometry, real-time PCR, western blotting, and ELISA were performed to assess determinants related to PE manifestation, including sFlt-1, sEng, STAT-3, RORγt, SMAD-7, Foxp3, IL-17, IL-22, Ets-1, and miRNA-326. RESULTS: Our results showed that the miRNA-326 expression level increased in CD4+ Cells and Th17 in PE patients which downregulated Ets-1 expression that acts as a negative control for Th17 development. Furthermore, we showed that the number and expression level of Th17 s and transcription factor RORγt escalated, respectively. While Treg and its related transcription factor (Foxp3) demonstrated a decrease. Flow cytometry analysis illustrated that the Th17/Treg ratio increased in PE. Additionally, we demonstrated that expression and concentration levels of cytokines (IL-17 and IL22) and anti-angiogenic molecules (sEng and sFlt-1) soared in isolated CD4+ cells from PE patients, which could be correlated with PE pathogenicity. CONCLUSION: In conclusion, we comprehensively evaluated immunological factors and molecules involved in PE manifestation. Interestingly, the CD4+ T-cell subset could be an extra source of antiangiogenic factors for the maintenance of this hypertension disorder.

16.
Nanomedicine ; 34: 102384, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33771704

RESUMO

High concentrations of adenosine and interleukin (IL)-6 in the tumor microenvironment have been identified as one of the leading causes of cancer growth. Thus, we decided to inhibit the growth of cancer cells by inhibiting the production of adenosine and IL-6 in the tumor environment at the same time. For this purpose, we used chitosan-lactate-PEG-TAT (CLP-TAT) nanoparticles (NPs) loaded with siRNA molecules against CD73, an adenosine-producing enzyme, and IL-6. Proper physicochemical properties of the produced NPs led to high cell uptake and suppression of target molecules. Administration of these NPs to tumor-bearing mice (4T1 and CT26 models) greatly reduced the size of the tumor and increased the survival of the mice, which was accompanied by an increase in anti-tumor T lymphocyte responses. These findings suggest that combination therapy using siRNA-loaded CLP-TAT NPs against CD73 and IL-6 molecules could be an effective treatment strategy against cancer that needs further study.

17.
Nanomedicine ; 34: 102373, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33667724

RESUMO

HIF-1α and STAT3 are two of the critical factors in the growth, proliferation, and metastasis of cancer cells and play a crucial role in inhibiting anti-cancer immune responses. Therefore, we used superparamagnetic iron oxide (SPION) nanoparticles (NPs) coated with thiolated chitosan (ChT) and trimethyl chitosan (TMC) and functionalized with hyaluronate (H) and TAT peptide for delivery of siRNA molecules against STAT3 and HIF-1α to cancer cells both in vivo and in vitro. The results indicated that tumor cell transfection with siRNA-encapsulated NPs robustly inhibited proliferation and migration and induced apoptosis in tumor cells. Furthermore, simultaneous silencing of HIF-1α and STAT3 significantly repressed cancer development in two different tumor types (4T1 breast cancer and CT26 colon cancer) which were associated with upregulation of cytotoxic T lymphocytes and IFN-γ secretion. The findings suggest inhibiting the HIF-1α/STAT3 axis by SPION-TMC-ChT-TAT-H NPs as an effective way to treat cancer.

18.
Life Sci ; 276: 119437, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789145

RESUMO

In Coronavirus disease 2019 (COVID-19), a decreased number of regulatory T (Treg) cells and their mediated factors lead to a hyperinflammatory state due to overactivation of the inflammatory cells and factors during the infection. In the current study, we evaluated the Nanocurcumin effects on the Treg cell population and corresponding factors in mild and severe COVID-19 patients. To investigate the Nanocurcumin effects, 80 COVID-19 patients (40 at the severe stage and 40 at the mild stage) were selected and classified into Nanocurcumin and placebo arms. In both the Nanocurcumin and placebo groups, the Treg cell frequency, the gene expression of Treg transcription factor forkhead box P3 (FoxP3), and cytokines (IL-10, IL-35, and TGF-ß), as well as the serum levels of cytokines were measured before and after treatment. In both mild and severe COVID-19 patients, Nanocurcumin could considerably upregulate the frequency of Treg cells, the expression levels of FoxP3, IL-10, IL-35, and TGF-ß, as well as the serum secretion levels of cytokines in the Nanocurcumin-treated group compared to the placebo group. The abovementioned factors were remarkably increased in the post-treatment with Nanocurcumin before pre-treatment conditions. By contrast, it has been observed no notable alteration in the placebo group. Our findings revealed the SinaCurcumin® effective function in a significant increase in the number of Treg cells and their mediated factors in the Nanocurcumin group than in the placebo group in both mild and severe patients. Hence, it would be an efficient therapeutic agent in rehabilitating COVID-19 infected patients.


Assuntos
COVID-19/tratamento farmacológico , Curcumina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Idoso , COVID-19/imunologia , COVID-19/virologia , Citocinas/efeitos dos fármacos , Citocinas/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/imunologia , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Nanomedicina/métodos , RNA Viral/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Fator de Crescimento Transformador beta/imunologia
19.
Clin Immunol ; 226: 108712, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684527

RESUMO

In the past year, an emerging disease called Coronavirus disease 2019 (COVID-19), caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been discovered in Wuhan, China, which has become a worrying pandemic and has challenged the world health system and economy. SARS-CoV-2 enters the host cell through a specific receptor (Angiotensin-converting enzyme 2) expressed on epithelial cells of various tissues. The virus, by inducing cell apoptosis and production of pro-inflammatory cytokines, generates as cytokine storm, which is the major cause of mortality in the patients. This type of response, along with responses by other immune cell, such as alveolar macrophages and neutrophils causes extensive damage to infected tissue. Newly, a novel cell-based therapy by Mesenchymal stem cell (MSC) as well as by their exosomes has been developed for treatment of COVID-19 that yielded promising outcomes. In this review study, we discuss the characteristics and benefits of MSCs therapy as well as MSC-secreted exosome therapy in treatment of COVID-19 patients.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Exossomos/metabolismo , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Medicina de Precisão/métodos , Linfócitos B/imunologia , COVID-19/tratamento farmacológico , COVID-19/patologia , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Pandemias , SARS-CoV-2/patogenicidade , Linfócitos T/imunologia
20.
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.

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