Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to ...achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.
In recent years, nanoparticles (NPs) have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging.In this review, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.
Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, ...malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand–receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors. Antibodies against cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) were the first immunotherapeutics that achieved the US Food and Drug Administration approval. Preliminary clinical results with the blockers of additional immune checkpoint proteins, such as programmed cell death protein 1 (PD‐1) indicate extensive and different chances to boost antitumor immunity with the objective of conferring permanent clinical effects. This study provides an overview of the immune checkpoint pathways, including CTLA‐4, PD‐1, lymphocyte activation gene 3, T‐cell immunoglobulin and mucin domain 3, B7‐H3, and diacylglycerol kinase α and implications of their inhibition in the cancer therapy.
Recent advances in the understating of tumor immunology suggest that cancer immunotherapy is an effective treatment against various types of cancer. In particular, the remarkable successes of immune checkpoint‐blocking antibodies in clinical settings have encouraged researchers to focus on developing other various immunologic strategies to combat cancer. Checkpoints are a kind of control mechanisms whose functions are important in survival, initiation, intensification, and termination of the immune system activities in the body. Their stimulation or inhibition occasionally leads to immune cell survival and/or in contrary, they identify the survival of their target. To avoid the excessive activity of the immune system there are reciprocal receptors of these ligands on various cells.
Over the recent decades, the use of antibody–drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody–based treatment of various human tumors has presented dramatic ...efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR).
The use of antibody–drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody–based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR).
Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due ...to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.
Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and ...poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side‐effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long‐standing effectiveness is bring about many patients not receiving these drugs. Over the years, the stem cell‐based therapy has attained substantial clinical consideration because of its potential to treat numerous diseases. The stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell‐based therapy for osteoporosis has caught substantial attention, no clinical trial has been published on humans. The cell studies based on osteoporosis are primarily focused on osteoclastic activity and bone resorption procedures. Earlier, it was on osteoblastogenesis and in recent times, on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell‐based strategy in osteoporosis.
Stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell‐based therapy for osteoporosis has suggested substantial attention over the years, no clinical trial has been published in humans. The cell studies on the basis of osteoporosis are primarily attentive on osteoclastic activity and bone resorption procedures; at that point on osteoblastogenesis, and in recent times on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell‐based strategy in osteoporosis.
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.
The current study aimed to investigate the therapeutic effects of nanocurcumin on the frequency and responses of T helper (Th) 17 cells in mild and severe coronavirus disease 2019 (COVID‐19) patients. 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. Curcumin could reduce the frequency of Th17 cells and their related inflammatory factors in both mild and severe COVID‐19 patients.
In the current study, we aimed to identify nanocurcumin effects on microRNAs (miRNAs) in the peripheral blood of patients with relapsing‐remitting multiple sclerosis (RRMS). We intended to ...investigate the expression pattern of these miRNAs in experimental settings in vivo. The expression levels of the selected 27 miRNAs known to be involved in the regulation of immune responses were analyzed in 50 RRMS patients and 35 healthy controls. The miRNA expression profiles were investigated by quantitative PCR (qPCR) at baseline and after 6 months of nanocurcumin therapy. Our data revealed that the expression of a number of microRNAs including miR‐16, miR‐17‐92, miR‐27, miR‐29b, miR‐126, miR‐128, miR‐132, miR‐155, miR‐326, miR‐550, miR‐15a, miR‐19b, miR‐106b, miR‐320a, miR‐363, miR‐31, miR‐150, and miR‐340 is regulated by nanocurcumin. The results of the current work indicate that nanocurcumin is able to restore the expression pattern of dysregulated miRNAs in MS patients. We discovered that some miRNAs are deregulated in untreated patients compared with healthy controls and nanocurcumin‐treated patients. This is a new finding that might represent the potential contribution of these miRNAs to MS pathogenesis. Taken together, these data provide novel insights into miRNA‐dependent regulation of the function of B and T cells in MS disease and enrich our understanding of the effects mediated by a therapeutic approach that targets B and T cells.
In the current study, we aimed to identify nanocurcumin effects on microRNAs (miRNAs) in the peripheral blood of patients with relapsing‐remitting multiple sclerosis (RRMS). We intended to investigate the expression pattern of these miRNAs in experimental settings in vivo.
Osteosarcoma (OS) is the most common primary malignant tumor of the bone with a strong tendency to early metastasis, and occurs in growing bones more commonly in children and adolescents. Considering ...the limited therapeutic methods and lack of 100% success of these methods, developing innovative therapies with high efficacy and lower side effects is needed. Meanwhile, miRNAs and the studies indicating the involvement of miRNAs in OS development have attracted attentions as a result of the frequent abnormalities in expression of miRNAs in cancer. miRNAs are noncoding short sequences with lengths ranging from 18 to 25 nucleotides that play a very important role in cellular processes, such as proliferation, differentiation, migration, and apoptosis. MiRNAs can have either oncogenic or tumor suppressive role based on cellular function and targets. This review aimed to have overview on miR‐142 as a tumor suppressor in OS. Moreover, the genes involved in the disease, such as RAC1,
HMAG1,
MMP9,
MMP2, and
E‐cadherin, which have irregularities as a result of change in miR‐142 expression, and, thereby, result in increasing the proliferation, invasion, and metastasis of the cells in the tissues and OS cells will be discussed.
The current review aimed to have overview on miR‐142 as a tumor suppressor in osteosarcoma (OS). Additionally, the genes involved in the disease, such as RAC1, HMAG1, MMP9, MMP2, and E‐cadherin, which have irregularities as a result of change in miR‐142 expression, and, thereby, result in increasing the proliferation, invasion, and metastasis of the tumor cells in OS will be discussed.
Osteosarcoma (OS) is one of the most common bone tumors in children and adolescents that cause a high rate of mortality in this age group and tends to be metastatic, in spite of chemotherapy and ...surgery. The main reason for this can be returned to a small group of malignant cells called cancer stem cells (CSCs). OS‐CSCs play a key role in the resistance to treatment and relapse and metastasis through self‐renewal and differentiation abilities. In this review, we intend to go through the different aspects of this malignant disease, including the cancer stem cell‐phenotype, methods for isolating CSCs, signaling pathways, and molecular markers in this disease, and drugs showing resistance in treatment efforts of OS.
Osteosarcoma‐cancer stem cells play a key role in the resistance to treatment and relapse and metastasis through self‐renewal and differentiation abilities. In this review, we intend to go through the cancer stem cell‐phenotype, methods for isolating cancer stem cells, signaling pathways and molecular markers in this disease, and drugs showing resistance in treatment efforts of osteosarcoma.
Problem
Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To ...investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg‐related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women.
Methods
Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real‐time polymerase chain reaction (PCR). Enzyme‐linked immunosorbent assay (ELISA) was used to test the interleukin (IL)‐17, IL‐23, IL‐6, and IL‐10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry.
Results
PE patients exhibited a decreased number of Treg cells (p = 0.006), while Th17 cells were increased (
p = 0.004). Forkhead box P3 and
IL‐10 mRNA expressions were reduced (
p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor‐related orphan nuclear receptor γt, IL‐17, IL‐23, and IL‐6 were enhanced (
p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL‐6, IL‐17, and IL‐23 (
p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL‐10 in the supernatant of PBMCs of PE patients compared with control group (
p = 0.0011). There was significant upregulation of miR‐106b and miR‐326 (
p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group.
Conclusions
These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto‐maternal immune cross‐talk.
Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17/regulatory T cells is thought to play considerable roles in preeclampsia.
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