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Öğe Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy(AICHE Online Library, 2022) Ashrafizadeh, Milad; Hushmandi, Kiavash; Mirzaei, Sepideh; Bokaie, Saied; Bigham, Ashkan; Makvandi, Pooyan; Rabiee, Navid; Thakur, Vijay Kumar; Kumar, Alan Prem; Sharifi, Esmaeel; Varma, Rajender S.; Aref, Amir Reza; Wojnilowicz, Marcin; Zarrabi, Ali; Karimi-Maleh, Hassan; Voelcker, Nicolas H.; Mostafavi, Ebrahim; Orive, GorkaGreen chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.Öğe The circadian rhythm: an influential soundtrack in the diabetes story(Frontiers Media Sa, 2023) Hariri, Amirali; Mirian, Mina; Zarrabi, Ali; Kohandel, Mohammad; Amini-Pozveh, Maryam; Aref, Amir Reza; Tabatabaee, AliyeType 2 Diabetes Mellitus (T2DM) has been the main category of metabolic diseases in recent years due to changes in lifestyle and environmental conditions such as diet and physical activity. On the other hand, the circadian rhythm is one of the most significant biological pathways in humans and other mammals, which is affected by light, sleep, and human activity. However, this cycle is controlled via complicated cellular pathways with feedback loops. It is widely known that changes in the circadian rhythm can alter some metabolic pathways of body cells and could affect the treatment process, particularly for metabolic diseases like T2DM. The aim of this study is to explore the importance of the circadian rhythm in the occurrence of T2DM via reviewing the metabolic pathways involved, their relationship with the circadian rhythm from two perspectives, lifestyle and molecular pathways, and their effect on T2DM pathophysiology. These impacts have been demonstrated in a variety of studies and led to the development of approaches such as time-restricted feeding, chronotherapy (time-specific therapies), and circadian molecule stabilizers.Öğe Correction: The long and short non-coding RNAs modulating EZH2 signaling in cancer (Journal of Hematology & Oncology, (2022), 15, 1, (18), 10.1186/s13045-022-01235-1)(BioMed Central Ltd, 2022) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Hashemi, Farid; Zabolian, Amirhossein; Canadas, Israel; Zarrabi, Ali; Nabavi, Noushin; Aref, Amir Reza; Crea, Francesco; Wang, Yuzhuo; Ashrafizadeh, Milad; Kumar, Alan PremThe original article [1] contained an error in co-author, Farid Hashemi’s name which has since been corrected. © 2022, The Author(s).Öğe CRISPR technology: A versatile tool to model, screen, and reverse drug resistance in cancer(Elsevier Gmbh, 2023) Shirani-Bidabadi, Shiva; Tabatabaee, Aliye; Tavazohi, Nazita; Hariri, Amirali; Aref, Amir Reza; Zarrabi, Ali; Casarcia, NicoletteBackground: Drug resistance is a serious challenge in cancer treatment that can render chemotherapy a failure. Understanding the mechanisms behind drug resistance and developing novel therapeutic approaches are cardinal steps in overcoming this issue. Clustered regularly interspaced short palindrome repeats (CRISPR) gene-editing technology has proven to be a useful tool to study cancer drug resistance mechanisms and target the responsible genes. In this review, we evaluated original research studies that used the CRISPR tool in three areas related to drug resistance, namely screening resistance-related genes, generating modified models of resistant cells and animals, and removing resistance by genetic manipulation. We reported the targeted genes, study models, and drug groups in these studies. In addition to discussing different applications of CRISPR technology in cancer drug resistance, we analyzed drug resistance mechanisms and provided examples of CRISPR's role in studying them. Although CRISPR is a powerful tool for examining drug resistance and sensitizing resistant cells to chemo-therapy, more studies are required to overcome its disadvantages, such as off-target effects, immunotoxicity, and inefficient delivery of CRISPR/cas9 into the cells.Öğe Exosomes as promising nanostructures in diabetes mellitus: from insulin sensitivity to ameliorating diabetic complications(2022) Ashrafizadeh, Milad; Kumar, Alan Prem; Aref, Amir Reza; Zarrabi, Ali; Mostafavi, EbrahimDiabetes mellitus (DM) is among the chronic metabolic disorders that its incidence rate has shown an increase in developed and wealthy countries due to lifestyle and obesity. The treatment of DM has always been of interest, and significant effort has been made in this field. Exosomes belong to extracellular vesicles with nanosized features (30-150 nm) that are involved in cell-to-cell communication and preserving homeostasis. The function of exosomes is different based on their cargo, and they may contain lipids, proteins, and nucleic acids. The present review focuses on the application of exosomes in the treatment of DM; both glucose and lipid levels are significantly affected by exosomes, and these nanostructures enhance lipid metabolism and decrease its deposition. Furthermore, exosomes promote glucose metabolism and affect the level of glycolytic enzymes and glucose transporters in DM. Type I DM results from the destruction of ? cells in the pancreas, and exosomes can be employed to ameliorate apoptosis and endoplasmic reticulum (ER) stress in these cells. The exosomes have dual functions in mediating insulin resistance/sensitivity, and M1 macrophage-derived exosomes inhibit insulin secretion. The exosomes may contain miRNAs, and by transferring among cells, they can regulate various molecular pathways such as AMPK, PI3K/Akt, and ?-catenin to affect DM progression. Noteworthy, exosomes are present in different body fluids such as blood circulation, and they can be employed as biomarkers for the diagnosis of diabetic patients. Future studies should focus on engineering exosomes derived from sources such as mesenchymal stem cells to treat DM as a novel strategy.Öğe Gene regulation by antisense transcription: a focus on neurological and cancer diseases(Science Direct, 2022) Najaf, Sajad; Tan, Shing Cheng; Raee, Pourya; Rahmati, Yazdan; Asemani, Yahya; Lee, E. Hui Clarissa; Hushmandi, Kiavash; Aref, Amir RezaAdvances in high-throughput sequencing over the past decades have led to the identification of thousands of non-coding RNAs (ncRNAs), which play a major role in regulating gene expression. One emerging class of ncRNAs is the natural antisense transcripts (NATs), the RNA molecules transcribed from the opposite strand of a protein-coding gene locus. NATs are known to concordantly and discordantly regulate gene expression in both cis and trans manners at the transcriptional, post-transcriptional, translational, and epigenetic levels. Aberrant expression of NATs can therefore cause dysregulation in many biological pathways and has been observed in many genetic diseases. This review outlines the involvements and mechanisms of NATs in the pathogenesis of various diseases, with a special emphasis on neurodegenerative diseases and cancer. We also summarize recent findings on NAT knockdown and/or overexpression experiments and discuss the potential of NATs as promising targets for future gene therapies.Öğe Immunotherapeutic approaches in hepatocellular carcinoma: building blocks of hope in near future(Elsevier, 2023) Minaei, Neda; Ramezankhani, Roya; Tamimi, Atena; Piryaei, Abbas; Zarrabi, Ali; Aref, Amir Reza; Mostafavi, Ebrahim; Vosough, MassoudHepatocellular carcinoma (HCC) is the most common type of primary hepatic cancer and is among the major causes of mortality due to cancer. Due to the lack of efficient conventional therapeutic options for this cancer, particularly in advanced cases, novel treatments including immunotherapy have been considered. However, despite the encouraging clinical outcomes after implementing these innovative approaches, such as oncolytic viruses (OVs), adoptive cell therapies (ACT), immune checkpoint blockades (ICBs), and cancer vaccines, several factors have restricted their therapeutic effect. The main concern is the existence of an immunosuppressive tumor microenvironment (TME). Combination of different ICBs or ICBs plus tyrosine kinase inhibitors have shown promising results in overcoming these limiting factors to some extent. Combination of programmed cell death ligand-1 (PD-L1) antibody Atezolizumab and vascular endothelial growth factor (VEGF) antibody Bevacizumab has become the standard of care in the first-line therapy for untestable HCC, approved by regulatory agencies. This paper highlighted a wide overview of the direct and indirect immunotherapeutic strategies proposed for the treatment of HCC patients and the common challenges that have hindered their further clinical applications. © 2022 The AuthorsÖğe The long and short non-coding RNAs modulating EZH2 signaling in cancer(2022) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Hshemi, Farid; Zabolian, Amirhossein; Canadas, Israel; Zarrabi, Ali; Nabavi, Noushin; Aref, Amir Reza; Crea, Francesco; Wang, Yuzhuo; Ashrafizadeh, Milad; Kumar, Alan PremNon-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.Öğe Long non-coding RNAs and exosomal incRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling(Elsevier Science, 2022) Entezari, Maliheh; Ghanbarirad, Maryam; Taheriazam, Afshin; Sadrkhanloo, Mehrdokht; Zabolian, Amirhossein; Shekhi Beig Goharrizi, Mohammad Ali; Hushmandi, Kiavash; Aref, Amir Reza; Ashrafizadeh, Milad; Zarrabi, Ali; Nabavi, Noushin; Rabiee, Navid; Hashemi, Mehrdad; Samarghandian, SaeedAmong the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, weÖğe Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling(Elsevier, 2022) Entezari, Maliheh; Ghanbarirad, Maryam; Taheriazam, Afshin; Sadrkhanloo, Mehrdokht; Zabolian, Amirhossein; Goharrizi, Mohammad Ali Shekhi Beig; Hushmandi, Kiavash; Aref, Amir Reza; Ashrafizadeh, Milad; Zarrabi, Ali; Nabavi, Noushin; Rabiee, Navid; Hashemi, Mehrdad; Samarghandian, SaeedAmong the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, we discuss regulation of lncRNAs by anti-cancer drugs and genetic tools as well as the role of these factors in therapy response of lung cancer cells.Öğe Nanoliposomes as nonviral vectors in cancer gene therapy(John Wiley and Sons Inc, 2024) Yıldız, Safiye Nur; Entezari, Maliheh; Paskeh, Mahshid Deldar Abad; Mirzaei, Sepideh; Kalbasi, Alireza; Zabolian, Amirhossein; Hashemi, Farid; Hushmandi, Kiavash; Hashemi, Mehrdad; Raei, Mehdi; Goharrizi, Mohammad Ali Sheikh Beig; Aref, Amir Reza; Zarrabi, Ali; Ren, Jun; Orive, Gorka; Rabiee, Navid; Ertaş, Yavuz NuriNonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off-targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions. © 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.Öğe Non-coding RNA-based regulation of inflammation(Elsevier Science, 2022) Ashrafizadeh, Milad; Zarrabi, Ali; Mostafavi, Ebrahim; Aref, Amir Reza; Sethi, Gautam; Wang, Lingzhi; Tergaonkar, Vinaynflammation is a multifactorial process and various biological mechanisms and pathways participate in its development. The presence of inflammation is involved in pathogenesis of different diseases such as diabetes mellitus, cardiovascular diseases and even, cancer. Non-coding RNAs (ncRNAs) comprise large part of tran- scribed genome and their critical function in physiological and pathological conditions has been confirmed. The present review focuses on miRNAs, lncRNAs and circRNAs as ncRNAs and their potential functions in inflam- mation regulation and resolution. Pro-inflammatory and anti-inflammatory factors are regulated by miRNAs via binding to 3’-UTR or indirectly via affecting other pathways such as SIRT1 and NF-?B. LncRNAs display a similar function and they can also affect miRNAs via sponging in regulating levels of cytokines. CircRNAs mainly affect miRNAs and reduce their expression in regulating cytokine levels. Notably, exosomal ncRNAs have shown ca- pacity in inflammation resolution. In addition to pre-clinical studies, clinical trials have examined role of ncRNAs in inflammation-mediated disease pathogenesis and cytokine regulation. The therapeutic targeting of ncRNAs using drugs and nucleic acids have been analyzed to reduce inflammation in disease therapy. Therefore, ncRNAsÖğe Targeting AMPK signaling in ischemic/reperfusion injury: From molecular mechanism to pharmacological interventions(2022) Paskeh, Mahshid Deldar Abad; Asadi, Ava; Mirzaei, Sepideh; Hashemi, Mehrdad; Entezari, Maliheh; Raesi, Rasoul; Hushmandi, Kiavash; Zarrabi, Ali; Ertas, Yavuz Nuri; Aref, Amir Reza; Samarghandian, Saeed; Reiter, Russel J; Ren, JunIschemia is a pathological process in which blood supply to a particular organ is temporarily interrupted resulting in disturbed biological function and homeostasis of local tissues. Following ischemia, reperfusion and reoxygenation may occur which further worsens oxidative stress-mediated damage in cells and tissues. The combined processes are referred to as ischemia/reperfusion (I/R) injury. Immediate management and treatment of I/R is of utmost importance for preventing irreversible and extensive cellular damage. Apoptosis, inflammation and oxidative stress are the most validated pathologies associated with I/R. AMP-activated protein kinase (AMPK) modulates energy metabolism in cells and its activation occurs in response to elevated AMP and ADP levels. Aberrant levels of AMPK are noted in various pathological settings such as diabetes mellitus, cancer and neurological diseases. This review emphasizes AMPK signaling, its related molecular pathways and therapeutic utility during I/R. Activation of AMPK through phosphorylation prevents apoptosis and reduces oxidative stress and inflammation upon I/R. Inducing AMPK signaling normalizes mitochondrial function to inhibit cell death. Autophagy as a cytoprotective mechanism undergoes activation by AMPK/mTOR and AMPK/ULK1 pathways. AMPK reinforces the antioxidant defense capacity via Nrf2 signaling to counteract oxidative stress in I/R. Protective compounds including phytochemicals activate AMPK to alleviate I/R injury.
