Publications by authors named "Jamshid Gholizadeh Navashenaq"

33 Publications

Effect of propolis supplementation on athletic performance, body composition, inflammation, and oxidative stress following intense exercise: A triple-blind randomized clinical trial.

Food Sci Nutr 2021 Jul 8;9(7):3631-3640. Epub 2021 May 8.

Department of Health, Science and Research Branch AJA University of Medical Sciences Tehran Iran.

Background: Emerging evidence indicates that propolis as a novel potential antioxidant has unique benefits. This study aimed to evaluate the effect of propolis on oxidative stress, inflammation, body composition, and athletic performance in healthy active subjects.

Methods: This clinical trial was conducted on 54 male military cadets. Eligible subjects were randomly allocated to receive a single dose of 450 mg propolis twice daily for four weeks or a matching placebo containing microcrystalline cellulose. Cooper 12-min run test and running-based anaerobic sprint test were performed to measure aerobic and anaerobic performance. Blood samples were obtained immediately after Cooper's test to evaluate oxidative stress and inflammation status. Fat mass and fat-free mass were analyzed using bioelectrical impedance.

Results: Mean changes in fat mass, fat-free mass, anaerobic powers, fatigue index, and VO max did not differ significantly between the two groups after the adjustment for baseline values (P-value>0.05). A significant change was observed in plasma levels of IL-6 (-1.43 ± 0.11pg/mL), total oxidant status (-3.9 ± 0.2µmol/L), total antioxidant capacity (164 ± 12 µmol/L), malondialdehyde (-0.52 ± 0.03µmol/L), oxidative stress index (-0.45 ± 0.04), and glutathione (48.72±2µmol/L) in the propolis group compared with the placebo group after the adjustment for baseline values and weight changes (P-value<0.05). Although IL-10 concentrations had no significant changes in both groups, the ratio of IL-6/IL-10 significantly reduced in the propolis group compared with the placebo group (-0.174 ± 0.015 versus. 0.051 ± 0.014; P-value: 0.041).

Conclusions: Our results indicated that propolis might have beneficial effects on oxidative stress and inflammation following intense activities in healthy male subjects.
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http://dx.doi.org/10.1002/fsn3.2319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269685PMC
July 2021

Humoral immune mechanisms involved in protective and pathological immunity during COVID-19.

Hum Immunol 2021 Jul 1. Epub 2021 Jul 1.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.humimm.2021.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245343PMC
July 2021

in controlling Type 2 diabetes, cardiovascular, and rheumatoid arthritis diseases: Molecular aspects.

J Res Med Sci 2021 31;26:20. Epub 2021 Mar 31.

Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Oxidative stress is an important factor in the etiology of several chronic diseases that include cardiovascular disease (CVD), Type 2 diabetes (T2D), and rheumatoid arthritis (RA). Oxidative stress can lead to inflammation, and this can contribute to these chronic diseases. Reducing inflammation and oxidative stress may, therefore, be useful in the prevention and treatment of these conditions. One of the treatment options for chronic diseases is the use of traditional medicine and herbs, such as . This is one of the herbs that have recently been assessed for its ability to reduce inflammation and oxidative stress. We have reviewed the reported effects of on risk factors of chronic diseases (CVD, DM, and RA) with emphasis on molecular and cellular mechanisms in controlling inflammation and oxidative stress. Various mechanisms have been proposed to contribute to the beneficial properties of , including a reduction of lipid peroxidation via its antioxidant properties; agonist of peroxisome proliferator-activated receptor gamma in adipose tissue; activation of AMP-activated protein kinase, increased antioxidants, inhibition of nuclear factor-kappa B pathway; increased in interleukin-10 expression, CD4+ T-cell percentage, T regulatory cell percentage (CD4+ CD25+ T-cell) in peripheral blood, and CD4+/CD8+ ratio, but to prove this claim, it is necessary to conduct experimental and well-designed clinical trial studies with a larger sample size on the effects of on these chronic diseases.
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http://dx.doi.org/10.4103/jrms.JRMS_236_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240544PMC
March 2021

The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes for Orthopedic Diseases Treatment.

Stem Cell Rev Rep 2021 Jun 24. Epub 2021 Jun 24.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

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.
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http://dx.doi.org/10.1007/s12015-021-10185-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224994PMC
June 2021

Interleukin-25: New perspective and state-of-the-art in cancer prognosis and treatment approaches.

Cancer Med 2021 Jun 15. Epub 2021 Jun 15.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran.

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.
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http://dx.doi.org/10.1002/cam4.4060DOI Listing
June 2021

Effects of microwave technology on the subcutaneous abdominal fat and anthropometric indices of overweight adults: A clinical trial.

J Cosmet Dermatol 2021 May 22. Epub 2021 May 22.

Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background And Objective: Non-invasive body contouring devices have fewer side effects and are the new techniques for the treatment of obesity. The present study aimed to evaluate the effects of microwave technology on the abdominal obesity and anthropometric indices of overweight adults.

Materials And Methods: This clinical trial was conducted on 53 overweight adults aged 18-65 years who referred to Behbood Clinic in Tehran, Iran. The participants were exposed to microwave technology (radiofrequency: 2.5 GHz) based on a standard treatment protocol at three intervals (0, 20, and 40 days). Abdominal obesity, body mass index, waist-to-hip ratio, body fat mass, and fat thickness were measured at the beginning and 20, 40, and 60 days after the study. In addition, three-day dietary records were collected at intervals.

Results: In total, 77.6% of the subjects were female and 22.4% were male. The mean calorie intake of the participants was 2245.14 ± 1981.16 kcal/day. Microwave shock significantly reduced fat thickness in four abdominal areas (p < 0.001). Moreover, waist circumference (p < 0.001) and total fat thickness of the abdomen decreased (p = 0.003 and p = 0.002, respectively).

Conclusion: According to the results, microwave technology and radiofrequency could effectively reduce anthropometric indices. In general, the reduction of these indicators and weight may be more significant in men compared to women.
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http://dx.doi.org/10.1111/jocd.14245DOI Listing
May 2021

The effect of RGD-targeted and non-targeted liposomal Galbanic acid on the therapeutic efficacy of pegylated liposomal doxorubicin: From liposomal preparation to in-vivo studies.

Int J Pharm 2021 May 19;604:120710. Epub 2021 May 19.

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The anti-cancer therapeutic application of Galbanic acid (Gba) as a strong antiangiogenic sesquiterpene coumarin has been limited due to its low water solubility. This issue necessitates developing new liposomal formulations for the efficient delivery of Gba in vivo. In this study, various liposomal formulations were prepared by a thin-film hydration method, and Gba was incorporated into the liposomal bilayers, which consequently increased its release profile compared to formulations in our previous study prepared by remote loading methods. The most stable formulation with desired properties was selected and decorated with RGD peptide (cyclo [Arg-Gly-Asp-D-Tyr-Cys]) to target tumor vasculature actively. The fluorescently-labeled model liposomes showed that the targeting could improve the receptor-mediated endocytosis of the liposomes higher than those prepared in our previous study in vitro in human umbilical vein endothelial cells (HUVECs), which was confirmed by chicken chorioallantoic membrane angiogenesis (CAM) model in vivo. Although not significant, it also could increase the accumulation of liposomes in colon tumors. In BALB/c mice bearing colon cancer, not only non-targeted Gba liposomes but also even RGD-targeted ones combinatorial therapy with pegylated liposomal doxorubicin could improve the anti-tumor efficacy as compared to their monotherapy. These outcomes have strong consequences for cancer therapy.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120710DOI Listing
May 2021

Chemokine CXCL14; a double-edged sword in cancer development.

Int Immunopharmacol 2021 Apr 28;97:107681. Epub 2021 Apr 28.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.intimp.2021.107681DOI Listing
April 2021

Genomic instability in cancer: molecular mechanisms and therapeutic potentials.

Curr Pharm Des 2021 Apr 25. Epub 2021 Apr 25.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

DNA damage usually happens in all cell types, which may originate from endogenous sources, (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to large structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. DNA repair, as the most significant response to DNA damage, provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes are serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered as a crucial factor in the carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss about the potential promises of these mechanisms in finding new targets for the treatment of cancer.
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http://dx.doi.org/10.2174/1381612827666210426100206DOI Listing
April 2021

Curcumin and cancer; are long non-coding RNAs missing link?

Prog Biophys Mol Biol 2021 Apr 21. Epub 2021 Apr 21.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran. Electronic address:

Despite significant signs of progress in cancer treatment over the past decade, either cancer prevalence or mortality continuously grow worldwide. Current anti-cancer agents show insignificant effectiveness, followed by serious side effects. It is important to find new, highly efficient pharmacological agents to increase cancer patients' clinical outcomes. Curcumin, a polyphenolic compound, has gained growing attention because of its anti-cancer properties. Curcumin can hinder the development, migration, and metastasis of cancer cells. The anti-cancer effects of curcumin are principally attributed to the regulation of several cellular signaling pathways, including MAPK/PI3K/Akt, Wnt/β-catenin, JAK/STAT, and NF-ĸB signaling pathways. Furthermore, curcumin can affect the expression and function of tumor-suppressive and oncogenic long non-coding RNAs (lncRNAs). In this study, we briefly reviewed the modulatory effect of curcumin on dysregulated tumor-supportive and tumor-suppressive lncRNAs in several cancers. It is hoped that a better understanding of curcumin's anti-cancer properties would pave the way for the development of a therapeutic approach in cancer.
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http://dx.doi.org/10.1016/j.pbiomolbio.2021.04.001DOI Listing
April 2021

CXC chemokine ligand 16: a Swiss army knife chemokine in cancer.

Expert Rev Mol Med 2021 Apr 21;23:e4. Epub 2021 Apr 21.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran.

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.
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http://dx.doi.org/10.1017/erm.2021.7DOI Listing
April 2021

Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2.

Life Sci 2021 Jul 28;276:119437. Epub 2021 Mar 28.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

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-β), 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-β, 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.
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http://dx.doi.org/10.1016/j.lfs.2021.119437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005319PMC
July 2021

HTLV-1 oncovirus-host interactions: From entry to the manifestation of associated diseases.

Rev Med Virol 2021 Mar 19. Epub 2021 Mar 19.

Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T lymphotropic virus type-1 (HTLV-1) is a well-known human oncovirus, associated with two life-threatening diseases, adult T cell leukaemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The study of this oncogenic virus is significant from two different aspects. First, HTLV-1 can be considered as a neglected public health problem, which may spread slowly worldwide. Second, the incidence of HTLV-1 associated diseases due to oncogenic effects and deterioration of the immune system towards autoimmune diseases are not fully understood. Furthermore, knowledge about viral routes of transmission is important for considering potential interventions, treatments or vaccines in endemic regions. In this review, novel characteristics of HTLV-1, such as the unusual infectivity of virions through the virological synapse, are discussed in the context of the HTLV-1 associated diseases (ATL and HAM/TSP).
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http://dx.doi.org/10.1002/rmv.2235DOI Listing
March 2021

Shedding more light on the role of Midkine in hepatocellular carcinoma: New perspectives on diagnosis and therapy.

IUBMB Life 2021 Apr 3;73(4):659-669. Epub 2021 Mar 3.

Student Research Committee, Bam University of Medical Sciences, Bam, Iran.

One of the most common malignant tumors is hepatocellular carcinoma (HCC). Progression of HCC mainly results from highly complex molecular and pathological pathways. Midkine (MDK) is a growth factor that impacts viability, migration, and other cell activities. Since MDK has been involved in the inflammatory responses, it has been claimed that MDK has a crucial role in HCC. MDK acts as an anti-apoptotic factor, which mediates tumor cell viability. In addition, MDK blocks anoikis to promote metastasis. There is also evidence that MDK is involved in angiogenesis. It has been shown that the application of anti-MDK approaches might be promising in the treatment of HCC. Besides, due to the elevated expression in HCC, MDK has been proposed as a biomarker in the prognosis and diagnosis of HCC. In this review, we will discuss the role of MDK in HCC. It is hoped that the development of new strategies concerning MDK-based therapies will be promising in HCC management.
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http://dx.doi.org/10.1002/iub.2458DOI Listing
April 2021

A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease.

Nutr Metab (Lond) 2021 Feb 23;18(1):22. Epub 2021 Feb 23.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran.

One of the most prevalent diseases worldwide without a fully-known mechanism is non-alcoholic fatty liver disease (NAFLD). Recently, long non-coding RNAs (lncRNAs) have emerged as significant regulatory molecules. These RNAs have been claimed by bioinformatic research that is involved in biologic processes, including cell cycle, transcription factor regulation, fatty acids metabolism, and-so-forth. There is a body of evidence that lncRNAs have a pivotal role in triglyceride, cholesterol, and lipoprotein metabolism. Moreover, lncRNAs by up- or down-regulation of the downstream molecules in fatty acid metabolism may determine the fatty acid deposition in the liver. Therefore, lncRNAs have attracted considerable interest in NAFLD pathology and research. In this review, we provide all of the lncRNAs and their possible mechanisms which have been introduced up to now. It is hoped that this study would provide deep insight into the role of lncRNAs in NAFLD to recognize the better molecular targets for therapy.
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http://dx.doi.org/10.1186/s12986-021-00552-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903707PMC
February 2021

The role of Non-coding Genome in Cancer-associated Fibroblasts; state-of-the-art and perspectives in cancer targeted therapy.

Curr Drug Targets 2021 Feb 15. Epub 2021 Feb 15.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam. Iran.

Cancer-associated fibroblasts (CAFs) are senescent fibroblasts in tumor nest, which trigger a signaling center to remodel a desmoplastic tumor niche. CAF's functions in cancer are closely similar to myofibroblasts during the wound healing process. They can produce cytokine, enzymes, and protein- or RNA-containing exosomes to alter the function of surrounding cells. Non-coding RNAs, including microRNAs and long non-coding RNAs, modulate pathologic mechanisms in cancer. Dysregulation of these RNAs influences the formation and function of CAFs. Furthermore, it has been demonstrated that CAFs, by releasing non-coding RNAs-containing exosomes, affect the tumor cells' behavior. CAFs also secrete mediators such as chemokines to alter the expression of non-coding RNAs in the tumor microenvironment. This study aimed to discuss the role of non-coding RNAs in CAF development in cancer situations. Additionally, we are going to shed light on the therapeutic approaches to develop the strategies based-on the alteration of non-coding RNAs in cancer.
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http://dx.doi.org/10.2174/1389450122666210216091953DOI Listing
February 2021

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility.

Int J Rheum Dis 2021 Apr 7;24(4):567-581. Epub 2021 Feb 7.

Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Background: Genetic polymorphisms in the endoplasmic reticulum aminopeptidase gene ERAP2 has been attributed with the etiopathogenesis of ankylosing spondylitis (AS). Here we assessed the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with AS predisposition in Iranian patients and determined their effect on the inflammatory state of the patients.

Methods: For genotyping of rs2548538, rs2287988, and rs17408150 SNPs using a real-time allelic discrimination approach, DNA was extracted from the whole blood of 250 AS patients and 250 healthy individuals. RNA of the peripheral blood mononuclear cells was separated, cDNA was synthesized, and transcriptional levels of cytokines, including interleukin (IL)-17A, IL-23, IL-10, and transforming growth factor-β, were measured. Enzyme-linked immunosorbent assay was used to measure the serum concentration on the cytokines.

Results: Three ERAP2 gene SNPs were not associated significantly with AS risk. Nonetheless, rs2287988 and rs17408150 SNPs showed statistically significant association with susceptibility to the disease in those AS patients who were positive for human leukocyte antigen (HLA)-B27. Transcriptional level and serum concentration of IL-17A and IL-23 were higher, but those of IL-10 were lower in both AS patients and the HLA-B27-positive patient group relative to the control group. Nevertheless, ERAP2 gene SNPs in the HLA-B27-positive AS patients did not affect the transcription level and serum concentration of cytokines.

Conclusions: ERAP2 gene rs2287988 and rs17408150 SNPs are associated with susceptibility to AS, but they are probably not determining the levels of IL-17A, IL-23, and IL-10 in this disease.
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http://dx.doi.org/10.1111/1756-185X.14079DOI Listing
April 2021

Postprandial effects of macronutrient composition meals on the metabolic responses and arterial stiffness indices of lean and obese male adults: a protocol of a pilot study.

Pilot Feasibility Stud 2021 Feb 3;7(1):41. Epub 2021 Feb 3.

Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Prior studies have shown that meal composition may affect the metabolic responses and arterial stiffness indices, and these responses may be different in lean and obese adults. The primary objective of this study is to determine the feasibility of conducting a trial to compare the effect of three test meals in lean and obese men. Due to the lack of a comprehensive study that concurrently compares metabolic responses and vascular stiffness indices after receiving three different meals in lean and obese men, this pilot study will be conducted with a three-phase parallel design, aiming to investigate the effects of meal composition on the metabolic parameters and arterial stiffness indices of lean and obese adults.

Methods: This pilot, a parallel clinical trial will be performed on 24 male adults aged 18-35 years since January 2021 and will continue until March 2021 who are disease-free and selected based on the inclusion and exclusion criteria at Mashhad University of Medical Sciences, Iran. The subjects will complete three interventions at a 1-week interval, including high carbohydrate (70% carbohydrates, 10% protein, 20% fat), high protein (30% protein, 50% carbohydrates, 20% fat), and high-fat meal (50% fat, 40% carbohydrates, 10% protein). Postprandial effects will be assessed within 360 min after each meal, including the energy expenditure component (resting energy expenditure, thermic effects of feeding, respiratory quotient, and substrate oxidation) and arterial stiffness indices (augmentation index and pulse wave velocity). In addition, blood sampling will be performed to measure glucose, insulin, free fatty acids, and lipid profile.

Discussion: The differences in the postprandial responses can affect the metabolic and vascular parameters due to different meal compositions, thereby providing beneficial data for the establishment of new strategies in terms of nutritional education and metabolic/vascular improvement. Also, the results from this pilot study will inform intervention refinement and efficacy testing of the intervention in a larger randomized controlled trial.

Trial Registration: Iranian Registry of Clinical Trials; code: IRCT20190818044552N1 ; registered on August 26, 2019.
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http://dx.doi.org/10.1186/s40814-021-00787-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856746PMC
February 2021

The role of myeloid-derived suppressor cells in rheumatoid arthritis: An update.

Life Sci 2021 Mar 20;269:119083. Epub 2021 Jan 20.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the late stages of the disease, it can be associated with several complications. Although the exact etiology of RA is unknown, various studies have been performed to understand better the immunological mechanisms involved in the pathogenesis of RA. At the onset of the disease, various immune cells migrate to the joints and increase the recruitment of immune cells to the joints by several immunological mediators such as cytokines and chemokines. The function of specific immune cells in RA is well-established. The shift of immune responses to Th1 or Th17 is one of the most essential factors in the development of RA. Myeloid-derived suppressor cells (MDSCs), as a heterogeneous population of myeloid cells, play a regulatory role in the immune system that inhibits T cell activity through several mechanisms. Various studies have been performed on the function of these cells in RA, which in some cases have yielded conflicting results. Therefore, the purpose of this review article is to comprehensively understand the pro-inflammatory and anti-inflammatory functions of MDSCs in the pathogenesis of RA.
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http://dx.doi.org/10.1016/j.lfs.2021.119083DOI Listing
March 2021

The role of non-coding genome in the behavior of infiltrated myeloid-derived suppressor cells in tumor microenvironment; a perspective and state-of-the-art in cancer targeted therapy.

Prog Biophys Mol Biol 2021 May 28;161:17-26. Epub 2020 Nov 28.

Student Research Committee, Bam University of Medical Sciences, Bam, Iran; Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran. Electronic address:

Cancer is one of the healthcare problems that affect many communities around the world. Many factors contribute to cancer development. Besides, these factors are counted as the main impediment in cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) are one of these impediments. MDSCs inhibit the immune responses through various mechanisms such as inhibitory cytokine release and nitric oxide metabolite production. Several factors are involved in forming these cells, including tumor secreted cytokine and chemokines, transcription factors, and non-coding RNA. In the meantime, micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the vital gene regulatory elements that affect gene expression. In this study, we are going to discuss the role of miRNAs and lncRNAs in MDSCs development in a cancer situation. It is hoped that miRNA and lncRNAs targeting may prevent the growth and development of these inhibitory cells in the cancer environment.
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http://dx.doi.org/10.1016/j.pbiomolbio.2020.11.006DOI Listing
May 2021

Protective effects of propolis on hepatic steatosis and fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) evaluated by real-time two-dimensional shear wave elastography: A randomized clinical trial.

Phytother Res 2021 Mar 9;35(3):1669-1679. Epub 2020 Nov 9.

Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, while no drugs have been approved for its treatment. The pieces of evidence indicate that propolis as a novel anti-inflammatory agent might be a promising candidate to treat NAFLD. We aimed to evaluate the efficacy of propolis on hepatic steatosis and fibrosis in patients with NAFLD. This randomized clinical trial was conducted on 54 patients with NAFLD. Patients were randomly assigned to receive propolis tablets at a dose of 250 mg twice daily for 4 months or placebo. The improvement in hepatic steatosis and fibrosis was evaluated using two-dimensional shear wave elastography. Improvement in the hepatic steatosis was significantly higher in the propolis group than the placebo group, even after adjustment for baseline value and changes in weight, energy intake, and physical activity (odds ratio [OR]: 5.67; 95% confidence intervals [CI]: 1.41-22.8; p = .014). A significant reduction was observed on the liver stiffness in the propolis group (-0.65 ± 0.56 kPa; p = .001), whereas it increased in the placebo group (0.27 ± 0.59 kPa; p = .037). Also, the intake of propolis significantly decreased high-sensitivity C-reactive protein (hs-CRP) levels compared with the placebo group (-0.371; 95%CI: -0.582 to -0.16 mg/L; p = .01). Changes in serum levels of fasting blood sugar, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, cholesterol, and triglyceride did not differ significantly between the two groups (p > .05). There was no significant improvement in insulin resistance in both groups (p > .05). Propolis seems to have protective effects on hepatic steatosis and fibrosis and to reduce the serum levels of hs-CRP in patients with NAFLD.
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http://dx.doi.org/10.1002/ptr.6937DOI Listing
March 2021

Molecular and cellular mechanisms of the effects of Propolis in inflammation, oxidative stress and glycemic control in chronic diseases.

Nutr Metab (Lond) 2020 12;17:65. Epub 2020 Aug 12.

Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Vakil Abad Blvd., Opposite to Mellat Park, Mashhad, 99199-91766 Iran.

Propolis is a sticky, resinous material gather from plants and is blended with wax and other constituents. It is reported to have anti-inflammatory, anti-oxidative and blood glucose-lowering properties. This review aims to summarise evidences for the cellular and molecular mechanism of Propolis in inflammation, oxidative stress, and glycemic control. Propolis stimulate the production and secretion of anti-inflammatory cytokines and to inhibit the production of inflammatory cytokines and due to its various antioxidant and poly-phenolic compounds may has a role in control and treating some of the chronic diseases. Most studies have shown that Propolis may affect metabolic factors including plasma insulin levels, and it has proposed that it could be used in the prevention and treatment of T2D Mellitus. In general, to demonstrate the definite effects of Propolis on chronic diseases, more studies are required using larger sample sizes and various doses of Propolis, using better characterized and standardized agents.
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http://dx.doi.org/10.1186/s12986-020-00485-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425411PMC
August 2020

Combination therapy with liposomal doxorubicin and liposomal vaccine containing E75, an HER-2/neu-derived peptide, reduces myeloid-derived suppressor cells and improved tumor therapy.

Life Sci 2020 Jul 7;252:117646. Epub 2020 Apr 7.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells causing resistance to immunotherapies in cancer tumors. In the current study, various immunogenic and therapeutic features of the combination therapies with non-liposomal Doxorubicin (Dox) and the E75 immunogenic peptide (Pep), derived from the human epidermal receptor-2 (HER-2), are investigated in parallel with their liposomal formulations (Lip-Dox (Doxil®) and Lip-Pep). Therefore, triple injection doses of Lip-Pep were preceded with Dox and Lip-Dox injections in TUBO/breast tumor-bearing BALB/c mice. Chemotherapy with either Dox or Lip-Dox reduced the frequency of MDSCs, the level of reactive oxygen species (ROS), and MDSCs-associated genes of Arg1, iNOS, S100A8, S100A9. Whereas Lip-Pep + Dox and Lip-Pep + Lip-Dox treatments synergistically potentiated the immunized splenocytes to produce INF-γ and enhanced the frequency of the anti-tumor CD8 and CD4 T cells as opposed to both chemotherapy and immunotherapy regimens. Chemo-immunotherapy increased the number of tumor-infiltrating lymphocytes (TILs) and reduced the level of CD25 FoxP3 T regulatory cells. Taken together, chemo-immunotherapy was the optimum treatment for the limitation of tumor progression as they targeted more cancer-related immune players.
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http://dx.doi.org/10.1016/j.lfs.2020.117646DOI Listing
July 2020

Nanoliposomal vaccine containing long multi-epitope peptide E75-AE36 pulsed PADRE-induced effective immune response in mice TUBO model of breast cancer.

Eur J Cancer 2020 04 4;129:80-96. Epub 2020 Mar 4.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The main goal of peptide-based cancer vaccines is to induce the immune system and activation of effective T cell responses against cancerous cells. Nevertheless, the potency of peptide vaccines is insufficient in most of cases and had limited clinical success. Therefore, the optimization of peptide-based cancer vaccine is essential to achieve powerful therapeutic outcomes. One strategy to enhanced potency of peptide vaccines and induce strong immune responses is the preparation of multi-epitope peptide formulation containing both Th- and cytotoxic T lymphocyte-induced responses epitope using suitable delivery system. For this reason, we studied the effect of Dioleoylphosphatidylethanolamine-containing liposomal vaccine composed of a mixture of short peptides AE36 and E75 (HER2/neu-derived peptides) and long multi-epitope peptide E75-AE36 (linkage of short peptides) in combination with a Pan HLA-DR epitope (PADRE) peptide. These formulations were examined using a series of subcutaneously injection to HER-2 TUBO-tumoured mice in prophylactic and therapeutic model. We observed that mice vaccinated with liposomal long peptide in combination with PADRE resulted in the superior induction of CD4 and CD8 T cells responses and significantly enhanced production of IFN-γ compared with liposomal short peptides and non-liposomal peptides formulations. Moreover, liposome-long peptide with PADRE led to the considerable reduction of tumour growth and lifespan induction in mouse model. In conclusion, our study indicated that liposomal formulation containing long multi-epitope peptide E75-AE36 with PADRE could be used as an effective multi-epitope prophylactic/therapeutic vaccine to generate potent antigen-specific CD8 T-cell immune response and may be introduced as a possible candidate peptide vaccine for breast cancer.
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http://dx.doi.org/10.1016/j.ejca.2020.01.010DOI Listing
April 2020

Doxil chemotherapy plus liposomal P5 immunotherapy decreased myeloid-derived suppressor cells in murine model of breast cancer.

Nanomedicine 2020 02 10;24:102150. Epub 2020 Jan 10.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Myeloid-derived suppressor cells (MDSCs) play a pivotal role in cancer. To overcome the problem of the MDSCs in the tumor microenvironment in this study, a combination of immunotherapy and chemotherapy was used. For this purpose, a liposomal formulation of P5 peptide and PEGylated liposomal doxorubicin (Doxil®) was utilized to treat mice bearing HER2 tumor model. The results revealed that Doxil® administration before immunotherapy had not only reduced the population and functions of the MDSCs in the spleen (P < 0.001) and the tumor microenvironment (P < 0.05) but had also supported further immunotherapy including enhanced CD4 (P < 0.01) and CD8 lymphocyte (P < 0.001) population and IFN-γ production (P < 0.001). This effect was also more pronounced with a liposomal P5 and Doxil® compared with free peptide and doxorubicin. In conclusion, the results demonstrated that Doxil® plus liposomal P5 could have a decreasing effect on MDSCs and tumor growth, and it could be beneficial in breast cancer treatment.
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http://dx.doi.org/10.1016/j.nano.2020.102150DOI Listing
February 2020

Effects of propolis and melatonin on oxidative stress, inflammation, and clinical status in patients with primary sepsis: Study protocol and review on previous studies.

Clin Nutr ESPEN 2019 10 5;33:125-131. Epub 2019 Jul 5.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Previous studies have explored the anti-inflammatory, anti-infection and oxidative stress reduction effects of propolis and melatonin in experimental studies. However, there are no studies at present exploring the effects of propolis and melatonin in patients with primary sepsis. The present study aims to evaluate the potential effects of propolis and melatonin as a pharmaceutical agent in patients with primary sepsis.

Methods/design: The study will be conducted as a randomized controlled clinical trial at the Imamreza hospital. Patients with primary sepsis, in four equal groups, will be recruited for the study. The treatment drugs are propolis and melatonin and the placebo. The following primary and secondary outcome measures will be evaluated: APACHE II Score, SOFA score, NUTRIC score, inflammatory factors, and oxidative stress markers.

Discussion: We describe the protocol for a clinical trial design evaluating the effects of simultaneous administration of propolis and melatonin in patients with primary sepsis. The result of the present study, positive or negative, should provide a step change in the evidence guiding current and future policies regarding the use of propolis and melatonin as an auxiliary treatment in patients with primary sepsis.

Trial Registration: Iranian Registry of Clinical Trials: IRCT20181025041460N1. Registered on 6 November 2018.
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http://dx.doi.org/10.1016/j.clnesp.2019.06.007DOI Listing
October 2019

MicroRNAs as important regulators of the NLRP3 inflammasome.

Prog Biophys Mol Biol 2020 01 15;150:50-61. Epub 2019 May 15.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Inflammasomes are a group of cytosolic multi-protein signaling complexes that regulate maturation of the interleukin (IL)-1 family cytokines IL-1β and IL-18 through activation of inflammatory caspase-1. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is the best characterized and consists of several key components that are assembled and activated in response to different endogenous and exogenous signals. The NLRP3 inflammasome is common to a number of human inflammatory diseases and its targeting may lead to novel anti-inflammatory therapy. NLRP3 inflammasome activation is tightly regulated by different mechanisms especially post-transcriptional modulation via microRNAs (miRNA). MicroRNAs are small endogenous noncoding RNAs that are 21-23 nucleotides in length and control the expression of various genes through binding to the 3'-untranslated regions of the respective mRNA and subsequent post-transcriptional regulation. MicroRNAs have recently been recognized as crucial regulators of the NLRP3 inflammasome. In this review, we summarize the current understanding of the role of miRNAs in the regulation of NLRP3 inflammasome complexes and their impact on the pathogenesis of inflammatory disease processes.
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http://dx.doi.org/10.1016/j.pbiomolbio.2019.05.004DOI Listing
January 2020

MPL nano-liposomal vaccine containing P5 HER2/neu-derived peptide pulsed PADRE as an effective vaccine in a mice TUBO model of breast cancer.

J Control Release 2019 06 15;303:223-236. Epub 2019 Apr 15.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Liposomal peptide-based vaccines can potentially suppress cancer cells proliferation in the host. To enhance the effectiveness of vaccination against cancer, additional strategies should also be employed. One strategy to promote peptide-based vaccine efficacy and induce powerful immune responses, is simultaneous activation of CD4 and CD8 T cells. To address this problem, we tested the efficacy of a nano-liposomal vaccine containing P5 peptide, a cytotoxic T lymphocytes (CTL) specific peptide derivative of rat HER2/neu protein, Pan HLA-DR (PADRE) peptide, a universal CD4 T helper cell epitope and monophosphoryl lipid A (MPL) a toll-like receptor 4 ligand. We observed potent CD8 T cell immune responses in TUBO mice vaccinated with liposomal P5 peptide in combination with PADRE and MPL. Also, this formulation remarkably improved anti-tumor effects against cells overexpressing HER2 in BALB/c mice compared to liposomal vaccine containing P5 only. Furthermore, we found that vaccination with Lip-P5- Integrated PADRE-MPL formulation significantly induced IFN-γ production, increased CD8 T cells numbers and enhanced survival compared to other groups of treated mice. In conclusion, our study indicated that Lip-P5-Integrated PADRE-MPL, after further confirmatory investigations, could be employed as a promising vaccine to generate potent CTL anti-tumor immune responses that could be beneficial to treatment of HER2 breast cancer.
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http://dx.doi.org/10.1016/j.jconrel.2019.04.019DOI Listing
June 2019

Possible molecular mechanisms of glucose-lowering activities of Momordica charantia (karela) in diabetes.

J Cell Biochem 2019 Feb 20. Epub 2019 Feb 20.

Department of Modern Sciences and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Diabetes mellitus is a highly prevalent metabolic disorder which is characterized by impaired glucose tolerance, with a relative or absolute insulin deficiency and profound changes in the metabolism of macronutrients. Traditional and complementary medicine is therapeutic strategies that have both been applied to improving glycemic control. Momordica charantia is one of the plant-based, folk medicines that used for improving glycemic control. We aimed to review, the effects of M. charantia on blood glucose with a clarification of the molecular pathways involved. Of the compounds derived from the plants, the insulin-like peptide, charantin, and the alkaloid vicine, have been reported to have hypoglycemic effects. Different mechanisms contribute to the antidiabetic activities of M. charantia, these include increasing pancreatic insulin secretion, decreasing insulin resistance and increasing peripheral and skeletal muscle cell glucose utilization, inhibition of intestinal glucose absorption and suppressing of key enzymes in the gluconeogenic pathways.
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http://dx.doi.org/10.1002/jcb.28483DOI Listing
February 2019

Targeted-nanoliposomal combretastatin A4 (CA-4) as an efficient antivascular candidate in the metastatic cancer treatment.

J Cell Physiol 2019 Jan 29. Epub 2019 Jan 29.

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

A number of antiangiogenic drugs have been approved by the Food and Drug Administration which are used in cancer therapy, and variety of other agents in several stages of clinical development or in preclinical assessment. Among these, combretastatin A4 (CA-4) is an under-researched inhibitor of angiogenesis that shows potential activity in the treatment of advanced tumors with migration capacity. However, its clinical application has been limited due to poor water solubility, low bioavailability, rapid metabolism, and systemic elimination. During the last decade, numerous investigations have been done to overcome these problems by using different CA-4 delivery systems or developing produgs of CA-4 or its structural analogs. Nevertheless, these strategies could not be efficient out of the undesired side effects on normal tissues. Nanoliposomal CA-4 not only benefits from the advantage of using liposomal drugs as opposed to free drugs but also can accumulate in the tumor site via specific targeting ligands, which leads to efficient targeting and enhancement of bioavailability. To the best of our knowledge, we consider an important attempt to understand different factors that might influence the CA-4 loading and release pattern of liposomes and the consequent results in tumor therapy. In this review, we shed light on various studied liposomal CA-4 formulations showing application thereof in cancer treatment.
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http://dx.doi.org/10.1002/jcp.28230DOI Listing
January 2019