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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 Combination therapy using nanomaterials and stem cells to treat spinal cord injuries(Elsevier Science, 2022) Zarepour, Arezou; Bal Öztürk, Ayça; Koyuncu Irmak, Duygu; Yaşayan, Gökçen; Gökmen, Aylin; Karaöz, Erdal; Zarepour, Atefeh; Zarrabi, Ali; Mostafavi, EbrahimAs a part of the central nervous system, the spinal cord (SC) provides most of the communications between the brain and other parts of the body. Any damage to SC interrupts this communication, leading to serious problems, which may remain for the rest of their life. Due to its significant impact on patients’ quality of life and its exorbitant medical costs, SC injury (SCI) is known as one of the most challengeable diseases in the world. Thus, it is critical to introduce highly translatable therapeutic platforms for SCI treatment. So far, different strategies have been introduced, among which utilizing various types of stem cells is one of the most interesting ones. The capability of stem cells to differentiate into several types of cell lines makes them promising candidates for the regeneration of injured tissues. One of the other interesting and novel strategies for SCI treatment is the appli- cation of nanomaterials, which could appear as a carrier for therapeutic agents or as a platform for culturing the cells. Combining these two approaches, stem cells and nanomaterials, could provide promising therapeutic strategies for SCI management. Accordingly, in this review we have summarized some of the recent advance- ments in which the applications of different types of stem cells and nanomaterials, alone and in combination forms, were evaluated for SCI treatment.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 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 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 A Novel Vision of Reinforcing Nanofibrous Masks with Metal Nanoparticles: Antiviral Mechanisms Investigation(Springernature, 2023) Hadinejad, Farinaz; Morad, Hamed; Jahanshahi, Mohsen; Zarrabi, Ali; Pazoki-Toroudi, Hamidreza; Mostafavi, EbrahimPrevention of spreading viral respiratory disease, especially in case of a pandemic such as coronavirus disease of 2019 (COVID-19), has been proved impossible without considering obligatory face mask-wearing protocols for both healthy and contaminated populations. The widespread application of face masks for long hours and almost everywhere increases the risks of bacterial growth in the warm and humid environment inside the mask. On the other hand, in the absence of antiviral agents on the surface of the mask, the virus may have a chance to stay alive and be carried to different places or even put the wearers at risk of contamination when touching or disposing the masks. In this article, the antiviral activity and mechanism of action of some of the potent metal and metal oxide nanoparticles in the role of promising virucidal agents have been reviewed, and incorporation of them in an electrospun nanofibrous structure has been considered an applicable method for the fabrication of innovative respiratory protecting materials with upgraded safety levels.