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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 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 Doxorubicin-loaded graphene oxide nanocomposites in cancer medicine: stimuli-responsive carriers, co-delivery and suppressing resistance(2022) Ashrafizadeh, Milad; Saebfar, Hamidreza; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Zabolian, Amirhossein; Zarrabi, AliIntroduction: The application of doxorubicin (DOX) in cancer therapy has been limited due to its drug resistance and poor internalization. Graphene oxide (GO) nanostructures have the capacity for DOX delivery while promoting its cytotoxicity in cancer. Areas covered: The favorable characteristics of GO nanocomposites, preparation method, and application in cancer therapy are described. Then, DOX resistance in cancer is discussed. The GO-mediated photothermal therapy and DOX delivery for cancer suppression are described. Preparation of stimuli-responsive GO nanocomposites, surface functionalization, hybrid nanoparticles, and theranostic applications are emphasized in DOX chemotherapy. Expert opinion: Graphene oxide nanoparticle-based photothermal therapy maximizes the anti-cancer activity of DOX against cancer cells. Apart from DOX delivery, GO nanomaterials are capable of loading anti-cancer agents and genetic tools to minimize drug resistance and enhance the cytolytic impact of DOX in cancer eradication. To enhance DOX accumulation in cancer cells, stimuli-responsive (redox-, light-, enzyme- and pH-sensitive) GO nanoparticles have been developed for DOX delivery. Further development of targeted delivery of DOX-loaded GO nanomaterials against cancer cells may be achieved by surface modification of polymers such as polyethylene glycol, hyaluronic acid, and chitosan. Doxorubicin-loaded GO nanoparticles have demonstrated theranostic potential for simultaneous diagnosis and therapy. Hybridization of GO with other nanocarriers such as silica and gold nanoparticles further broadens their potential anti-cancer therapy applications.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 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 Long noncoding RNAs (lncRNAs) in pancreatic cancer progression(Elsevier Science, 2022) Ashrafizadeh, Milad; Rabiee, Navid; Prem Kumar, Alan; Sethi, Gautam; Zarrabi, Ali; Wang, YuzhuoLong noncoding RNAs (lncRNAs) are RNA molecules involved in gene regulation at transcriptional, post-transcriptional, and epigenetic levels. lncRNAs participate in regulating apoptosis and autophagy in pancreatic cancer (PCa) and can promote and/or decrease the proliferation rate of tumor cells. The metastasis of PCa cells is tightly regulated by lncRNAs and they can affect the mechanism of epithelial-mesenchymal transition (EMT) to modulate metastasis. The drug resistance of PCa cells, especially to gemcitabine, can be affected by lncRNAs. In addition, lncRNAs enriched in exosomes can be transferred among tumor cells to regulate their proliferation and metastasis. Antitumor compounds, such as curcumin and ginsenosides, can regulate lncRNA expression in PCa therapy. As we discuss here, the expression level of lncRNAs can be considered as both a diagnostic and prognostic tool in patients with PCa. Teaser: We discuss the role of long noncoding RNAs in the proliferation, invasion, and therapy response of pancreatic cancer cells, evaluating their prognostic and diagnostic functions in the clinical course of this disease.Öğe Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia(Wiley-Blackwell, 2021) Kirtonia, Anuradha; Ashrafizadeh, Milad; Hushmandi, Kiavash; Zabolian, Amirhossein; Bejandi, Atefe K.; Rani, Reshma; Pandey, Amit K.; Baligar, Prakash; Kumar, Vinit; Das, Bhudev C.; Garg, ManojAcute myeloid leukemia (AML) is a common hematological disorder with heterogeneous nature that resulted from blocked myeloid differentiation and an enhanced number of immature myeloid progenitors. During several decades, different factors, including cytogenetic, genetic, and epigenetic have been reported to contribute to the pathogenesis of AML by inhibiting the differentiation and ensuring the proliferation of myeloid blast cells. Recently, long noncoding RNAs (lncRNAs) have been considered as potential diagnostic, therapeutic, and prognostic factors in different human malignancies including AML. Altered expression of lncRNAs is correlated with the transformation of hematopoietic stem and progenitor cells into leukemic blast cells because of their distinct role in the key cellular processes. We discuss the significant role of lncRNAs in the proliferation, survival, differentiation, leukemic stem cells in AML and their involvement in different molecular pathways (insulin-like growth factor type I receptor, FLT3, c-KIT, Wnt, phosphatidylinositol 3-kinase/protein kinase-B, microRNAs), and associated mechanisms such as autophagy, apoptosis, and glucose metabolism. In addition, we aim to highlight the role of lncRNAs as reliable biomarkers for diagnosis, prognosis, and drug resistance for precision medicine in AML.Öğe Mission impossible for cellular internalization: When porphyrin alliance with UiO-66-NH2 MOF gives the cell lines a ride(Elsevier, 2022) Ahmadi, Sepideh; Jajarmi, Vahid; Ashrafizadeh, Milad; Zarrabi, Ali; Haponiuk, Józef T.; Saeb, Mohammad Reza; Lima, Eder C.; Rabiee, Mohammad; Rabiee, NavidIs it possible to accelerate cell internalization by hybridization of nanomaterials? Herein we support the realization of using metal-organic frameworks (MOFs) with the assistance of rigid porphyrin structure (H2TMP) aimed at drug loading, drug release, relative cell viability, and targeted in vitro drug delivery. There are several MOFs, i.e., UiO-66-NH2 (125 ± 12.5 nm), UiO-66-NH2 @H2TMP (160 ± 14 nm), UiO-66-NH2 @H2TMP@DOX, and UiO-66-NH2 @H2TMP@DOX@RO were synthesized and characterized applying HEK-293, HT-29, MCF-7, and MCF-10A cell lines. MTT investigations proved a significantly higher relative cell viability for H2TMP-aided leaf-extract-coated nanocarriers (above 62 % relative cell viability). Furthermore, the rigid H2TMP structure improved drug loading capacity by 24 % through an enhanced hydrogen bond, van der Waals, and ?-? interactions. The in vitro targeted drug delivery experiments were conducted on HT-29 and MCF-7 cell lines. First, nanocarriers were treated with HT-29 cells, where UiO-66-NH2 @H2TMP@DOX@RO appeared as the best nanocarrier. Then, the selected nanocarrier was extracted from the HT-29 cell line and treated with the MCF-7 cell line. For the first time, the DOX remained inside the UiO-66-NH2 @H2TMP@DOX@RO after successful delivery to the HT-29 cell lines was observed on the MCF-7 cell line, and the second targeted drug delivery was performed. The results of this survey can enlighten the future ahead of cell internalization in MOF-based hybrid nanostructures. © 2022 Elsevier B.V.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 bladder cancer therapy: Challenges and opportunities(John Wiley and Sons Inc, 2022) Ashrafizadeh, Milad; Zarrabi, Ali; Karimi-Maleh, Hassan; Taheriazam, Afshin; Mirzaei, SepidehUrological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo-loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH-, redox-, and light-responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review. © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.Öğe (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 Nanotechnological approaches in prostate cancer therapy: Integration of engineering and biology(Elsevier B.V., 2022) Ashrafizadeh, Milad; Aghamiri, Shahin; Tan, Shing Cheng; Zarrabi, Ali; Sharifi, EsmaeelNanocarriers have received special attention in biomedicine for the treatment of various diseases, especially cancer, as one of the leading causes of death worldwide. Nanocarriers can improve the potential of contemporary strategies in cancer therapy and also provide new methods for diagnosis and biosensing. The present review focuses on the biomedical application of nanocarriers in the treatment of prostate cancer (PCa), one of the most common urological cancers in men. The chemotherapeutic and radiotherapeutic potentials in PCa may be improved using nanocarriers by providing targeted drug delivery and inducing PCa cells' sensitivity via induction of cell death. Delivery of nucleic acid drugs such as siRNA, shRNA and CRISPR/Cas9 system by nanocarriers in PCa therapy enhances the intracellular accumulation of these therapeutics and increases their efficacy in gene expression regulation. The high proliferation rate and metastasis of PCa cells result in poor prognosis. They may be dually suppressed by nanocarriers, as nanoplatforms facilitate co-delivery of drugs and gene therapeutics in PCa suppression. Selectivity toward PCa cells may be enhanced via surface modification of the nanocarriers to facilitate internalization via endocytosis. In addition to their applications for PCa treatment, nanocarriers mediate the detection of biomarkers for PCa diagnosis. © 2022 Elsevier LtdÖğe 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 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 Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response(Wiley, 2023) Ashrafizadeh, Milad; Mohan, Chakrabhavi D.; Rangappa, Shobith; Zarrabi, Ali; Hushmandi, Kiavash; Kumar, Alan Prem; Sethi, GautamGastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number of deaths worldwide. STAT3 is an oncogenic transcription factor that promotes the transcription of genes associated with proliferation, antiapoptosis, survival, and metastasis. STAT3 is overactivated in many human malignancies including GI tumors which accelerates tumor progression, metastasis, and drug resistance. Research in recent years demonstrated that noncoding RNAs (ncRNAs) play a major role in the regulation of many signaling pathways including the STAT3 pathway. The major types of endogenous ncRNAs that are being extensively studied in oncology are microRNAs, long noncoding RNAs, and circular RNAs. These ncRNAs can either be tumor-promoters or tumor-suppressors and each one of them imparts their activity via different mechanisms. The STAT3 pathway is also tightly modulated by ncRNAs. In this article, we have elaborated on the tumor-promoting role of STAT3 signaling in GI tumors. Subsequently, we have comprehensively discussed the oncogenic as well as tumor suppressor functions and mechanism of action of ncRNAs that are known to modulate STAT3 signaling in GI cancers.Öğe Stimuli-responsive liposomal nanoformulations in cancer therapy: Pre-clinical & clinical approaches(Elsevier, 2022) Ashrafizadeh, Milad; Delfi, Masoud; Zarrabi, Ali; Sharifi, Esmaeel; Rabiee, Navid; Paiva-Santos, Ana Cláudia; Kumar, Alan Prem; Hushmandi, Kiavash; Nazarzadeh Zare, Ehsan; Makvandi, PooyanThe site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of >40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients.Öğe Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response(2022) Ashrafizadeh, Milad; Deldar Abad Paskeh, Mahshid; Mirzaei, Sepideh; Gholami, Mohammad Hossein; Zarrabi, AliProstate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a "self-degradation" mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients.Öğe Wnt/?-Catenin signaling as a driver of hepatocellular carcinoma progression: an emphasis on molecular pathways(Dove Medical Press, 2021) Deldar Abad Paskeh, Mahshid; Mirzaei, Sepideh; Ashrafizadeh, Milad; Zarrabi, Ali; Sethi, GautamLiver cancers cause a high rate of death worldwide and hepatocellular carcinoma (HCC) is considered as the most common primary liver cancer. HCC remains a challenging disease to treat. Wnt/?-catenin signaling pathway is considered a tumor-promoting factor in various cancers; hence, the present review focused on the role of Wnt signaling in HCC, and its association with progression and therapy response based on pre-clinical and clinical evidence. The nuclear translocation of ?-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of CTNNB1 gene encoding ?-catenin and its overexpression can lead to HCC progression. ?-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, ?-catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that ?-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate ?-catenin signaling in HCC. Anti-cancer agents inhibit ?-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of ?-catenin and its gene mutation (CTNBB1) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/?-catenin signaling in HCC therapy.
