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Öğe Cervical cancer progression is regulated by SOX transcription factors: Revealing signaling networks and therapeutic strategies(Elsevier Science, 2021) Paskeh, Mahshid Deldar Abad; Mirzaei, Sepideh; Gholami, Mohammad Hossein; Zarrabi, Ali; Zabolian, Amirhossein; Hashemi, Mehrdad; Hushmandi, KiavashCervical cancer is the fourth common gynecologic cancer and is considered as second leading cause of death among women. Various strategies are applied in treatment of cervical cancer including radiotherapy, chemotherapy and surgery. However, cervical cancer cells demonstrate aggressive behavior in advanced phases, requiring novel strategies in their elimination. On the other hand, SOX proteins are transcription factors capable of regulating different molecular pathways and their expression varies during embryogenesis, disease development and carcinogenesis. In the present review, our aim is to reveal role of SOX transcription factors in cervical cancer. SOX transcription factors play like a double-edged sword in cancer. For instance, SOX9 possesses both tumor-suppressor and tumor-promoting role in cervical cancer. Therefore, exact role of each SOX members in cervical cancer has been discussed to direct further experiments for revealing other functions. SOX proteins can regulate proliferation and metastasis of cervical cancer cells. Furthermore, response of cervical cancer cells to chemotherapy and radiotherapy is tightly regulated by SOX transcription factors. Different downstream targets of SOX proteins such as Wnt signaling, EMT and Hedgehog have been identified. Besides, upstream mediators such as microRNAs, lncRNAs and circRNAs can regulate SOX expression in cervical cancer. In addition to pre-clinical studies, role of SOX transcription factors as prognostic and diagnostic tools in cervical cancer has been shown.Öğe Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug-gene interaction networks analysis(Nature, 2022) MotieGhader, Habib; Tabrizi-Nezhadi, Parinaz; Abad Paskeh, Mahshid Deldar; Baradaran, Behzad; Mokhtarzadeh, Ahad; Hashemi, Mehrdad; Lanjanian, Hossein; Jazayeri, Seyed Mehdi; Maleki, Masoud; Khodadadi, Ehsan; Nematzadeh, Sajjad; Maghsoudloo, Mazaher; Masoudi-Nejad, Ali; Kiani, FarzadLung cancer is the most common cancer in men and women. This cancer is divided into two main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Around 85 to 90 percent of lung cancers are NSCLC. Repositioning potent candidate drugs in NSCLC treatment is one of the important topics in cancer studies. Drug repositioning (DR) or drug repurposing is a method for identifying new therapeutic uses of existing drugs. The current study applies a computational drug repositioning method to identify candidate drugs to treat NSCLC patients. To this end, at frst, the transcriptomics profle of NSCLC and healthy (control) samples was obtained from the GEO database with the accession number GSE21933. Then, the gene co-expression network was reconstructed for NSCLC samples using the WGCNA, and two signifcant purple and magenta gene modules were extracted. Next, a list of transcription factor genes that regulate purple and magenta modules’ genes was extracted from the TRRUST V2.0 online database, and the TF–TG (transcription factors–target genes) network was drawn. Afterward, a list of drugs targeting TF–TG genes was obtained from the DGIdb V4.0 database, and two drug–gene interaction networks, including drug-TG and drug-TF, were drawn. After analyzing gene co-expression TF–TG, and drug–gene interaction networks, 16 drugs were selected as potent candidates for NSCLC treatment. Out of 16 selected drugs, nine drugs, namely Methotrexate, Olanzapine, Haloperidol, Fluorouracil, Nifedipine, Paclitaxel, Verapamil, Dexamethasone, and Docetaxel, were chosen from the drug-TG sub-network. In addition, nine drugs, including Cisplatin, Daunorubicin, Dexamethasone, Methotrexate, Hydrocortisone, Doxorubicin, Azacitidine, Vorinostat, and Doxorubicin Hydrochloride, were selected from the drug-TF sub-network. Methotrexate and Dexamethasone are common in drug-TG and drug-TF sub-networks. In conclusion, this study proposed 16 drugs as potent candidates for NSCLC treatment through analyzing gene co-expression, TF–TG, and drug–gene interaction networks.Öğe Exosome-mediated miR-200a delivery into TGF-?-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression(Academic Press Inc Elsevier Science, 2023) Mirzaei, Sepideh; Gholami, Mohammad Hossein; Aghdaei, Hamid Asadzadeh; Hashemi, Mehrdad; Parivar, Kazem; Karamian, Amin; Zarrabi, AliExosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential reg-ulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miR-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miR-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-beta for EMT induction and then, these cells cultured with miR-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading effi-ciency of 5.92 +/- 4.6%. The TGF-beta treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miR-200a expression in AGS cells. Mechanistically, miR-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of beta-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01), leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miR-200a delivery that is of importance for preventing migration and invasion of GC cells.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 Molecular landscape of LncRNAs in prostate cancer: A focus on pathways and therapeutic targets for intervention(PMC, 2022) Mirzaei, Sepideh; Abad Paskeh, Mahshid Deldar; Okina, Elena; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Hashemi, Mehrdad; Kalu , Azuma; Zarrabi, Ali; Nabav, Noushin; Rabiee, Navid; Sharifi, Esmaeel; Karimi-Maleh, Hassan; Ashrafizadeh, Milad; Kumar, Alan Prem; Wang, YuzhuoBackground: One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterog? enous and progressive natures. Genetic and epigenetic changes play signifcant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation. Aim of review: The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined. Key scientifc concepts of review: The aberrant expression of lncRNAs in prostate cancer has been well-docu? mented and progression rate of tumor cells are regulated via afecting STAT3, NF-?B, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarkerÖğe (Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy(Wiley, 2023) Ashrafizadeh, Milad; Zarrabi, Ali; Bigham, Ashkan; Taheriazam, Afshin; Saghari, Yalda; Mirzaei, Sepideh; Hashemi, MehrdadBreast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life-threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli-responsive nanocarriers, including pH-, redox-, and light-sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon-, lipid-, polymeric- and metal-based nanostructures, which are different in terms of biocompatibility and delivery efficiency.Öğe Non-coding RNA-Mediated N6-Methyladenosine (m6A) deposition: A pivotal regulator of cancer, impacting key signaling pathways in carcinogenesis and therapy response(Keai Publishing Ltd, 2024) Hashemi, Mehrdad; Daneii, Pouria; Zandieh, Mohammad Arad; Raesi, Rasoul; Zahmatkesh, Neda; Bayat, Mehrsa; Abuelrub, AnwarThe emergence of RNA modifications has recently been considered as critical post-transcriptional regulations which governed gene expression. N6-methyladenosine (m6A) modification is the most abundant type of RNA modification which is mediated by three distinct classes of proteins called m6A writers, readers, and erasers. Accumulating evidence has been made in understanding the role of m6A modification of non-coding RNAs (ncRNAs) in cancer. Importantly, aberrant expression of ncRNAs and m6A regulators has been elucidated in various cancers. As the key role of ncRNAs in regulation of cancer hallmarks is well accepted now, it could be accepted that m6A modification of ncRNAs could affect cancer progression. The present review intended to discuss the latest knowledge and importance of m6A epigenetic regulation of ncRNAs including mircoRNAs, long non-coding RNAs, and circular RNAs, and their interaction in the context of cancer. Moreover, the current insight into the underlying mechanisms of therapy resistance and also immune response and escape mediated by m6A regulators and ncRNAs are discussed.Öğe Non-coding RNAs and macrophage interaction in tumor progression(Elsevier Ireland Ltd, 2022) Entezari, Maliheh; Sadrkhanloo, Mehrdokht; Rashidi, Mohsen; Asnaf, Sholeh Etehad; Taheriazam, Afshin; Hashemi, Mehrdad; Ashrafizadeh, Milad; Zarrabi, Ali; Rabiee, Navid; Hushmandi, Kiavash; Mirzaei, Sepideh; Sethi, GautamThe macrophages are abundantly found in TME and their M2 polarization is in favor of tumor malignancy. On the other hand, non-coding RNAs (ncRNAs) can modulate macrophage polarization in TME to affect cancer progression. The miRNAs can dually induce/suppress M2 polarization of macrophages and by affecting various molecular pathways, they modulate tumor progression and therapy response. The lncRNAs can affect miRNAs via sponging and other molecular pathways to modulate macrophage polarization. A few experiments have also examined role of circRNAs in targeting signaling networks and affecting macrophages. The therapeutic targeting of these ncRNAs can mediate TME remodeling and affect macrophage polarization. Furthermore, exosomal ncRNAs derived from tumor cells or macrophages can modulate polarization and TME remodeling. Suppressing biogenesis and secretion of exosomes can inhibit ncRNA-mediated M2 polarization of macrophages and prevent tumor progression. The ncRNAs, especially exosomal ncRNAs can be considered as non-invasive biomarkers for tumor diagnosis. © 2022 Elsevier B.V.Öğe Non-coding RNAs targeting notch signaling pathway in cancer : from proliferation to cancer therapy resistance(Elsevier B.V., 2022) Hashemi, Mehrdad; Hasani, Sahar; Hajimazdarany, Shima; Mirmazloomi, Seyed Reza; Makvandy, Sara; Zabihi, Abbas; Goldoost, Yeganeh; Gholinia, Nazanin; Kakavand, Amirabbas; Tavakolpournegari, Alireza; Salimimoghadam, Shokooh; Nabavi, Noushin; Zarrabi, Ali; Taheriazam, Afshin; Entezari, Maliheh; Hushmandi, KiavashCancer is a challenging to treat disease with a high mortality rate worldwide, nevertheless advances in science has led to a decrease in the number of death cases caused by cancer. Aberrant expression of genes occurs during tumorigenesis therefore targeting the signaling pathways that regulate these genes' expression is of importance in cancer therapy. Notch is one of the signaling pathways having interactions with other vital cell signaling molecules responsible for cellular functions such as proliferation, apoptosis, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune evasion. Furthermore, the Notch pathway is involved in response to chemo- and radiotherapy. Thus, targeting the Notch signaling pathway in cancer therapy can be beneficial for overcoming the therapeutic gaps. Non-coding RNAs (ncRNAs) are a class of RNAs that include short ncRNAs (such as micro RNAs) and long ncRNAs (lncRNAs). MicroRNAs (miRNAs) are ~22 nucleotides in length while lncRNAs have more than 200 nucleotides. Both miRNAs and lncRNAs control vital cellular mechanisms in cells and affect various signaling pathways and Notch is among them. The current review aims to discuss the critical role of ncRNAs in the regulation of the Notch signaling pathway by focusing on different cancer hallmarks including proliferation, apoptosis, autophagy, EMT, invasion, metastasis, and resistance to therapies.Öğe Non-coding RNAs targeting notch signaling pathway in cancer: From proliferation to cancer therapy resistance(Elsevier, 2022) Hashemi, Mehrdad; Hasani, Sahar; Hajimazdarany, Shima; Mirmazloomi, Seyed Reza; Makvandy, Sara; Zabihi, Abbas; Goldoost, YeganehCancer is a challenging to treat disease with a high mortality rate worldwide, nevertheless advances in science has led to a decrease in the number of death cases caused by cancer. Aberrant expression of genes occurs during tumorigenesis therefore targeting the signaling pathways that regulate these genes' expression is of importance in cancer therapy. Notch is one of the signaling pathways having interactions with other vital cell signaling molecules responsible for cellular functions such as proliferation, apoptosis, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune evasion. Furthermore, the Notch pathway is involved in response to chemo- and radiotherapy. Thus, targeting the Notch signaling pathway in cancer therapy can be beneficial for overcoming the therapeutic gaps. Non-coding RNAs (ncRNAs) are a class of RNAs that include short ncRNAs (such as micro RNAs) and long ncRNAs (lncRNAs). MicroRNAs (miRNAs) are similar to 22 nucleotides in length while lncRNAs have more than 200 nucleotides. Both miRNAs and lncRNAs control vital cellular mechanisms in cells and affect various signaling pathways and Notch is among them. The current review aims to discuss the critical role of ncRNAs in the regulation of the Notch signaling pathway by focusing on different cancer hallmarks including proliferation, apoptosis, autophagy, EMT, invasion, metastasis, and resistance to therapies.Öğe Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity(Wiley, 2022) Mahabady, Mahmood K.; Mirzaei, Sepideh; Saebfar, Hamidreza; Gholami, Mohammad H.; Zabolian, Amirhossein; Hushmandi, Kiavash; Hashemi, Farid; Tajik, Fatemeh; Hashemi, Mehrdad; Kumar, Alan P.; Aref, Amir R.; Zarrabi, Ali; Khan, Haroon; Hamblin, Michael R.; Ertas, Yavuz Nuri; Samarghandian, SaeedThe identification of agents that can reverse drug resistance in cancer chemotherapy, andenhance the overall efficacy is of great interest. Paclitaxel (PTX) belongs to taxane family hat exerts an antitumor effect by stabilizing microtubules and inhibiting cell cycleprogression. However, PTX resistance often develops in tumors due to the over-expression of drug transporters and tumor?promoting pathways. Noncoding RNAs(ncRNAs) are modulators of many processes in cancer cells, such as apoptosis, migration,differentiation, and angiogenesis. In the present study, we summarize the effects ofncRNAs on PTX chemotherapy. MicroRNAs (miRNAs) can have opposite effects on PTXresistance (stimulation or inhibition) via influencing YES1, SK2, MRP1, and STAT3.Moreover, miRNAs modulate the growth and migration rates of tumor cells in regulatingPTX efficacy. PIWI?interacting RNAs, small interfering RNAs, and short?hairpin RNAs areother members of ncRNAs regulating PTX sensitivity of cancer cells. Long noncodingRNAs (LncRNAs) are similar to miRNAs and can modulate PTX resistance/sensitivity bytheir influence on miRNAs and drug efflux transport. The cytotoxicity of PTX againsttumor cells can also be affected by circular RNAs (circRNAs) and limitation is thatoncogenic circRNAs have been emphasized and experiments should also focus on onco?suppressor circRNAs.Öğe Pre-clinical and clinical importance of mir-21 in human cancers: tumorigenesis, therapy response, delivery approaches and targeting agents(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2023) Hashemi, Mehrdad; Mirdamadi, Motahare Sadat Ayat; Talebi, Yasmin; Khaniabad, Nasrin; Banaei, Gooya; Daneii, Pouria; Gholami, Sadaf; Ghorbani, Amin; Zarrabi, AliThe field of non-coding RNA (ncRNA) has made significant progress in understanding the pathogenesis of diseases and has broadened our knowledge towards their targeting, especially in cancer therapy. ncRNAs are a large family of RNAs with microRNAs (miRNAs) being one kind of endogenous RNA which lack encoded proteins. By now, miRNAs have been well-coined in pathogenesis and development of cancer. The current review focuses on the role of miR-21 in cancers and its association with tumor progression. miR-21 has both oncogenic and onco-suppressor functions and most of the experiments are in agreement with the tumor-promoting function of this miRNA. miR-21 primarily decreases PTEN expression to induce PI3K/Akt signaling in cancer progression. Overexpression of miR-21 inhibits apoptosis and is vital for inducing pro-survival autophagy. miR-21 is vital for metabolic reprogramming and can induce glycolysis to enhance tumor progression. miR-21 stimulates EMT mechanisms and increases expression of MMP-2 and MMP-9 thereby elevating tumor metastasis. miR-21 is a target of anti-cancer agents such as curcumin and curcumol and its down-regulation impairs tumor progression. Upregulation of miR-21 results in cancer resistance to chemotherapy and radiotherapy. Increasing evidence has revealed the role of miR-21 as a biomarker as it is present in both the serum and exosomes making them beneficial biomarkers for non-invasive diagnosis of cancer.Öğe Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action(Springer Science and Business Media Deutschland GmbH, 2022) Behroozaghdam, Mitra; Dehghani, Maryam; Zabolian, Amirhossein; Kamali, Davood; Javanshir, Salar; Hasani Sadi, Farzaneh; Hashemi, Mehrdad; Tabari, Teimour; Rashidi, Mohsen; Mirzaei, Sepideh; Zarepour, Atefeh; Zarrabi, Ali; De Greef, Danielle; Bishayee, AnupamBreast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, and/or doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RES’s promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES. Graphical abstract: [Figure not available: see fulltext.].Öğe 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.Öğe Targeting Nrf2 in ischemia-reperfusion alleviation: From signaling networks to therapeutic targeting(Elsevier Inc., 2022) Sadrkhanloo, Mehrdokht; Entezari, Maliheh; Orouei, Sima; Zabolian, Amirhossein; Mirzaie, Amirreza; Maghsoudloo, Amin; Raesi, Rasoul; Asadi, Neda; Hashemi, Mehrdad; Zarrabi, Ali; Khan, Haroon; Mirzaei, Sepideh; Samarghandian, SaeedThe nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of redox balance and it responds to various cell stresses that oxidative stress is the most well-known one. The Nrf2 should undergo nuclear translocation to exert its protective impacts and decrease ROS production. On the other hand, ischemic/reperfusion (I/R) injury is a pathological event resulting from low blood flow to an organ and followed by reperfusion. The I/R induces cell injury and organ dysfunction. The present review focuses on Nrf2 function in alleviation of I/R injury. Stimulating of Nrf2 signaling ameliorates I/R injury in various organs including lung, liver, brain, testis and heart. The Nrf2 enhances activity of antioxidant enzymes to reduce ROS production and prevent oxidative stress-mediated cell death. Besides, Nrf2 reduces inflammation via decreasing levels of pro-inflammatory factors including IL-6, IL-1? and TNF-?. Nrf2 signaling is beneficial in preventing apoptosis and increasing cell viability. Nrf2 induces autophagy to prevent apoptosis during I/R injury. Furthermore, it can interact with other molecular pathways including PI3K/Akt, NF-?B, miRNAs, lncRNAs and GSK-3? among others, to ameliorate I/R injury. The therapeutic agents, most of them are phytochemicals such as resveratrol, berberine and curcumin, induce Nrf2 signaling in I/R injury alleviation. © 2022
