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    Advancements and applications of upconversion nanoparticles in wound dressings
    (Royal Soc Chemistry, 2024) Gultekin, Hazal Ezgi; Yasayan, Gokcen; Bal-Ozurk, Ayca; Bigham, Ashkan; Simchi, Abdolreza (Arash); Zarepour, Atefeh; Iravani, Siavash
    Wound healing is a complex process that requires effective management to prevent infections and promote efficient tissue regeneration. In recent years, upconversion nanoparticles (UCNPs) have emerged as promising materials for wound dressing applications due to their unique optical properties and potential therapeutic functionalities. These nanoparticles possess enhanced antibacterial properties when functionalized with antibacterial agents, helping to prevent infections, a common complication in wound healing. They can serve as carriers for controlled drug delivery, enabling targeted release of therapeutic agents to the wound site, allowing for tailored treatment and optimal healing conditions. These nanoparticles possess the ability to convert near-infrared (NIR) light into the visible and/or ultraviolet (UV) regions, making them suitable for therapeutic (photothermal therapy and photodynamic therapy) and diagnostic applications. In the context of wound healing, these nanoparticles can be combined with other materials such as hydrogels, fibers, metal-organic frameworks (MOFs), graphene oxide, etc., to enhance the healing process and prevent the growth of microbial infections. Notably, UCNPs can act as sensors for real-time monitoring of the wound healing progress, providing valuable feedback to healthcare professionals. Despite their potential, the use of UCNPs in wound dressing applications faces several challenges. Ensuring the stability and biocompatibility of UCNPs under physiological conditions is crucial for their effective integration into dressings. Comprehensive safety and efficacy evaluations are necessary to understand potential risks and optimize UCNP-based dressings. Scalability and cost-effectiveness of UCNP synthesis and manufacturing processes are important considerations for practical applications. In addition, efficient incorporation of UCNPs into dressings, achieving uniform distribution, poses an important challenge that needs to be addressed. Future research should prioritize addressing concerns regarding stability and biocompatibility, efficient integration into dressings, rigorous safety evaluation, scalability, and cost-effectiveness. The purpose of this review is to critically evaluate the advantages, challenges, and key properties of UCNPs in wound dressing applications to provide insights into their potential as innovative solutions for enhancing wound healing outcomes. We have provided a detailed description of various types of smart wound dressings, focusing on the synthesis and biomedical applications of UCNPs, specifically their utilization in different types of wound dressings. In this review, we aim to showcase the potential and benefits of up-conversion nanoparticles (UCNPs) in advanced wound care applications.
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    Advances in phototheranostic agents: From imaging to targeted therapy
    (Elsevier Ltd., 2025) Samadzadeh, Meisam; Khosravi, Arezoo; Zarepour, Atefeh; Noei, Hadi; Sivakumar, Ponnurengam Malliappan; Iravani, Siavash; Zarrabi, Ali
    The recent evolution of phototheranostic agents represents a groundbreaking intersection of diagnostic imaging and targeted therapy, particularly in oncology. This review aims to elucidate the recent advances in phototheranostic agents, highlighting their dual functionality in imaging and targeted therapy. Despite significant progress, several challenges persist, including the optimization of agent specificity, light penetration in tissues, and the potential for off-target effects. The variability in tumor microenvironments presents a significant obstacle, complicating the development of universal phototheranostic agents. Moreover, concerns regarding the long-term stability, potential toxicity, and biocompatibility of these agents necessitate thorough evaluation and optimization. Notably, the complexity of designing nanoparticles that can effectively deliver both imaging and therapeutic modalities poses additional hurdles. Future perspectives in this field emphasize the need for innovative strategies to enhance agent stability, biocompatibility, and targeted delivery. Furthermore, ongoing research focuses on the development of novel light-based techniques and the exploration of combination therapies to improve treatment efficacy. By addressing these challenges, the potential of phototheranostic agents to transform personalized cancer therapy becomes increasingly promising. This review serves as a comprehensive overview of the current landscape, challenges, and future directions in phototheranostic research, ultimately aiming to inform and inspire further investigation in this dynamic field. © 2025 Elsevier Ltd
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    Anionic polysaccharides as delivery carriers for cancer therapy and theranostics: An overview of significance
    (Elsevier b.v., 2025) Sivakumar, Ponnurengam Malliappan; Zarepour, Atefeh; Akhter, Sohail; Perumal, Govindaraj; Khosravi, Arezoo; Balasekar, Premkumar; Zarrabi, Ali
    Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity. This review underscores the significance of anionic polysaccharides as essential components of the evolving landscape of cancer therapy and theranostics. These polymers can be tailored to carry a wide range of therapeutic cargo, including chemotherapeutic agents, nucleic acids, and imaging agents. Their negative charge enables electrostatic interactions with positively charged drugs and facilitates the formation of stable nanoparticles, liposomes, or hydrogels for controlled drug release. Additionally, their hydrophilic nature aids in prolonging circulation time, reducing drug degradation, and minimizing off-target effects. Besides, some of them could act as targeting agents or therapeutic compounds that lead to improved therapeutic performance. This review offers valuable information for researchers, clinicians, and biomedical engineers. It provides insights into the recent progress in the applications of anionic polysaccharide-based delivery platforms in cancer theranostics to transform patient outcomes.
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    Antimicrobial activity of blow spun PLA/gelatin nanofibers containing green synthesized silver nanoparticles against wound ınfection-causing bacteria
    (MDPI, 2022) Sardareh, Elham Alinezhad; Shahzeidi, Moloud; Ardestani, Mohammad Taha Salmanifard; Mousavi-Khattat, Mohammad; Zarepour, Atefeh; Zarrabi, Ali
    One of the main challenges in wound healing is the wound infection due to various causes, of which moisture is the most important reason. Owing to this fact, wound dressings that can collect wound moisture in addition to showing antibacterial properties have provided an important basis for wound healing research. In this study, gelatin and poly lactic acid (PLA) polymers were used in a wound dressing textile to provide gelation and structure strength properties, respectively. Meanwhile, silver nanoparticles (SNPs) synthesized through the green method were integrated into these fibers to provide the formed textile with antibacterial properties. Nanoparticles were made using donkey dung extract, and nanofibers were produced by the solution blow spinning method which has high production efficiency and low energy consumption among spinning methods. The produced nanoparticles were characterized and evaluated by UV-Vis, DLS, XRD, and FTIR methods, and the production of silver nanoparticles that were coated with metabolites in the extract was proven. In addition, the morphology and diameter of the resulted fibers and presence of nanoparticles were confirmed by the SEM method. The size and size distribution of the synthesized fibers were determined through analyzing SEM results. Gelatin nanofibers demonstrated a mean size of 743 nm before and 773 nm after nanoparticle coating. PLA nanofibers demonstrated a mean size of 57 nm before and 182 nm after nanoparticle coating. Finally, 335 nm was the mean diameter size of gelatin/PLA/SNPs nanofibers. Also, the textiles synthesized by PLA and gelatin which contained silver nanoparticles showed higher antibacterial activity against both gram-positive and gram-negative species compared to PLA and gelatin tissues without nanoparticles. Cytotoxicity test on L929 cells showed that silver nanoparticles incorporated textiles of PLA and gelatin show a very low level and non-significant toxicity compared to the free particles.
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    Application of 3D, 4D, 5D, and 6D bioprinting in cancer research: what does the future look like?
    (Royal Soc Chemistry, 2024) Khorsandi, Danial; Rezayat, Dorsa; Sezen, Serap; Ferrao, Rafaela; Khosravi, Arezoo; Zarepour, Atefeh; Khorsandi, Melika
    The application of three- and four-dimensional (3D/4D) printing in cancer research represents a significant advancement in understanding and addressing the complexities of cancer biology. 3D/4D materials provide more physiologically relevant environments compared to traditional two-dimensional models, allowing for a more accurate representation of the tumor microenvironment that enables researchers to study tumor progression, drug responses, and interactions with surrounding tissues under conditions similar to in vivo conditions. The dynamic nature of 4D materials introduces the element of time, allowing for the observation of temporal changes in cancer behavior and response to therapeutic interventions. The use of 3D/4D printing in cancer research holds great promise for advancing our understanding of the disease and improving the translation of preclinical findings to clinical applications. Accordingly, this review aims to briefly discuss 3D and 4D printing and their advantages and limitations in the field of cancer. Moreover, new techniques such as 5D/6D printing and artificial intelligence (AI) are also introduced as methods that could be used to overcome the limitations of 3D/4D printing and opened promising ways for the fast and precise diagnosis and treatment of cancer. Recent advancements pertaining to the application of 3D, 4D, 5D, and 6D bioprinting in cancer research are discussed, focusing on important challenges and future perspectives.
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    Application of Convergent Science and Technology toward Ocular Disease Treatment
    (Mdpi, 2023) Bal-Ozturk, Ayca; Ozcan-Bulbul, Ece; Gultekin, Hazal Ezgi; Cecen, Berivan; Demir, Ebru; Zarepour, Atefeh; Cetinel, Sibel
    Eyes are one of the main critical organs of the body that provide our brain with the most information about the surrounding environment. Disturbance in the activity of this informational organ, resulting from different ocular diseases, could affect the quality of life, so finding appropriate methods for treating ocular disease has attracted lots of attention. This is especially due to the ineffectiveness of the conventional therapeutic method to deliver drugs into the interior parts of the eye, and the also presence of barriers such as tear film, blood-ocular, and blood-retina barriers. Recently, some novel techniques, such as different types of contact lenses, micro and nanoneedles and in situ gels, have been introduced which can overcome the previously mentioned barriers. These novel techniques could enhance the bioavailability of therapeutic components inside the eyes, deliver them to the posterior side of the eyes, release them in a controlled manner, and reduce the side effects of previous methods (such as eye drops). Accordingly, this review paper aims to summarize some of the evidence on the effectiveness of these new techniques for treating ocular disease, their preclinical and clinical progression, current limitations, and future perspectives.
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    Association of clinical features with spike glycoprotein mutations in Iranian COVID-19 patients
    (MDPI, 2022) Ahangarzadeh, Shahrzad; Yousefi, Alireza; Ranjbar, Mohammad Mehdi; Dabiri, Arezou; Zarepour, Atefeh; Sadeghi, Mahmoud; Heidari, Elham; Mazrui, Fariba; Hosseinzadeh, Majid; Ataei, Behrooz; Zarrabi, Ali; Shariati, Laleh; Javanmard, Shaghayegh Haghjooy
    Background: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. Methods: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient's reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. Results: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. Conclusions: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease.
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    Autophagy and Biomaterials: A Brief Overview of the Impact of Autophagy in Biomaterial Applications
    (Mdpi, 2023) Pirmoradi, Leila; Shojaei, Shahla; Ghavami, Saeid; Zarepour, Atefeh; Zarrabi, Ali
    Macroautophagy (hereafter autophagy), a tightly regulated physiological process that obliterates dysfunctional and damaged organelles and proteins, has a crucial role when biomaterials are applied for various purposes, including diagnosis, treatment, tissue engineering, and targeted drug delivery. The unparalleled physiochemical properties of nanomaterials make them a key component of medical strategies in different areas, such as osteogenesis, angiogenesis, neurodegenerative disease treatment, and cancer therapy. The application of implants and their modulatory effects on autophagy have been known in recent years. However, more studies are necessary to clarify the interactions and all the involved mechanisms. The advantages and disadvantages of nanomaterial-mediated autophagy need serious attention in both the biological and bioengineering fields. In this mini-review, the role of autophagy after biomaterial exploitation and the possible related mechanisms are explored.
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    Bacterial nanocelluloses as sustainable biomaterials for advanced wound healing and dressings
    (Royal Society of Chemistry, 2024) Zarepour, Atefeh; Gök, Bahar; Budama Kılınç, Yasemin; Khosravi, Arezoo; Iravani, Siavash; Zarrabi, Ali
    Wound healing remains a significant clinical challenge, calling for innovative approaches to expedite the recovery process and improve patient outcomes. Bacterial nanocelluloses (BNCs) have emerged as a promising solution in the field of wound healing and dressings due to their unique properties such as high crystallinity, mechanical strength, high purity, porosity, high water absorption capacity, biodegradability, biocompatibility, sustainability, and flexibility. BNC-based materials can be applied for the treatment of different types of wounds, from second-degree burns to skin tears, biopsy sites, and diabetic and ischemic wounds. BNC-based dressings have exceptional mechanical properties such as flexibility and strength, which ensure proper wound coverage and protection. The renewable nature, eco-friendly production process, longer lifespan, and potential for biodegradability of BNCs make them a more sustainable alternative to conventional wound care materials. This review aims to provide a detailed overview on the application of BNC-based composites for wound healing and dressings via highlighting their ability as a carrier for delivery of different types of antimicrobial compounds as well as their direct effect on the healing process. Besides, it mentions some of the in vivo and clinical studies using BNC-based dressings and describes challenges related to the application of these materials as well as their future directions. © 2024 The Royal Society of Chemistry.
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    Biomedical applications of engineered heparin-based materials
    (Keai Publishing Ltd, 2024) Zare, Ehsan Nazarzadeh; Khorsandi, Danial; Zarepour, Atefeh; Yilmaz, Hulya; Agarwal, Tarun; Hooshmand, Sara; Mohammadinejad, Reza
    Heparin is a negatively charged polysaccharide with various chain lengths and a hydrophilic backbone. Due to its fascinating chemical and physical properties, nontoxicity, biocompatibility, and biodegradability, heparin has been extensively used in different fields of medicine, such as cardiovascular and hematology. This review highlights recent and future advancements in designing materials based on heparin for various biomedical ap-plications. The physicochemical and mechanical properties, biocompatibility, toxicity, and biodegradability of heparin are discussed. In addition, the applications of heparin-based materials in various biomedical fields, such as drug/gene delivery, tissue engineering, cancer therapy, and biosensors, are reviewed. Finally, challenges, opportunities, and future perspectives in preparing heparin-based materials are summarized.
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    Biosensor integrated brain-on-a-chip platforms: Progress and prospects in clinical translation
    (Elsevier Advanced Technology, 2023) Cecen, Berivan; Saygili, Ecem; Zare, Iman; Nejati, Omid; Khorsandi, Danial; Zarepour, Atefeh; Alarcin, Emine
    Because of the brain's complexity, developing effective treatments for neurological disorders is a formidable challenge. Research efforts to this end are advancing as in vitro systems have reached the point that they can imitate critical components of the brain's structure and function. Brain-on-a-chip (BoC) was first used for microfluidics-based systems with small synthetic tissues but has expanded recently to include in vitro simulation of the central nervous system (CNS). Defining the system's qualifying parameters may improve the BoC for the next generation of in vitro platforms. These parameters show how well a given platform solves the problems unique to in vitro CNS modeling (like recreating the brain's microenvironment and including essential parts like the blood-brain barrier (BBB)) and how much more value it offers than traditional cell culture systems. This review provides an overview of the practical concerns of creating and deploying BoC systems and elaborates on how these technologies might be used. Not only how advanced biosensing technologies could be integrated with BoC system but also how novel approaches will automate assays and improve point-of-care (PoC) diagnostics and accurate quantitative analyses are discussed. Key challenges providing opportunities for clinical translation of BoC in neurodegenerative disorders are also addressed.
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    Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study
    (Elsevier, 2024) Hosseini, Seyed Mohammad Reza; Heydari, Parisa; Namnabat, Mahtab; Azadani, Reyhaneh Nasr; Gharibdousti, Fateme Azimi; Rizi, Elmira Mousavi; Khosravi, Arezoo; Zarepour, Atefeh; Zarrabi, Ali
    Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-alpha, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-beta, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (-93%) was significantly greater than the control group (-58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.
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    Cellular targets and molecular activity mechanisms of bee venom in cancer: recent trends and developments
    (2022) Varol, Ayşegül; Sezen, Serap; Evcimen, Dilhan; Zarepour, Atefeh; Ulus, Gönül; Zarrabi, Ali; Badr, Gamal; Dastan, Sevgi Durna; Orbayoglu, Asya Gulistan
    Bee venom therapy is known as a traditional approach to curing many medical conditions such as arthritis, pain and rheumatism. Bee venom also provides promising potential for treating many cancers such as breast, lung, ovary, stomach, kidney, prostate, cervical, colon and esophageal cancers, osteosarcoma, leukemia, melanoma and hepatocellular carcinoma. We therefore focused not only on the molecular activity mechanisms and cellular targets of bee venom and its components, but also on modern solutions as cutting-edge nanotechnological advances to overcome existing bottlenecks, and the latest advances in the anticancer application of bee venom in clinical settings.
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    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, Ebrahim
    As 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.
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    A comparison study between doxorubicin and curcumin co-administration and co-loading in a smart niosomal formulation for MCF-7 breast cancer therapy
    (Elsevier, 2023) Saharkhiz, Shaghayegh; Zarepour, Atefeh; Nasri, Negar; Cordani, Marco; Zarrabi, Ali
    Chemotherapy agents often exhibit limited effectiveness due to their fast elimination from the body and nontargeted delivery. Emerging nanomaterials as drug delivery carriers open new expectancy to overcome these limitations in current chemotherapeutic treatments. In this study, we introduce and evaluate a smart pHresponsive niosomal formulation capable of delivering Doxorubicin (DOX) and Curcumin (CUR) in both individually and co-loaded forms. In particular, drug-loaded niosomes were prepared using thin-film hydration method and then characterized via different physicochemical analyses. The pH responsivity of the carrier was assessed by performing a drug release study in three different pH conditions (4, 6.5, and 7.4). Finally, the anticancer efficacy of the therapeutic compounds was evaluated through the MTT assay. Our results showed spherical particles with a size of about 200 nm and -2 mV surface charge. Encapsulation efficiency (EE%) of the nanocarrier was about 77.06 % and 79.08 % for DOX and CUR, respectively. The release study confirmed the pH responsivity of the carrier. The MTT assay results revealed about 39 % and 43 % of cell deaths after treatment with cur-loaded and dox-loaded niosomes, which increased to 74 % and 79 % after co-administration and coloading forms of drugs, respectively, exhibiting increased anticancer efficacy by selectively delivering DOX and CUR individually or in combination. Overall, these findings suggest that our nanoformulation holds the potential as a targeted and highly effective approach for cancer management and therapy, overcoming the limitations of conventional chemotherapy drugs.
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    Crosstalk of Transcriptional Regulators of Adaptive Immune System and microRNAs: An Insight into Differentiation and Development
    (Mdpi, 2023) Boshtam, Maryam; Rahimmanesh, Ilnaz; Shariati, Laleh; Najaflu, Malihe; Khanahmad, Hossein; Mirian, Mina; Zarepour, Atefeh
    MicroRNAs (miRNAs), as small regulatory RNA molecules, are involved in gene expression at the post-transcriptional level. Hence, miRNAs contribute to gene regulation of various steps of different cell subsets' differentiation, maturation, and activation. The adaptive immune system arm, which exhibits the most specific immune responses, is also modulated by miRNAs. The generation and maturation of various T-cell subsets concomitant with B-cells is under precise regulation of miRNAs which function directly on the hallmark genes of each cell subset or indirectly through regulation of signaling pathway mediators and/or transcription factors involved in this maturation journey. In this review, we first discussed the origination process of common lymphocyte progenitors from hematopoietic stem cells, which further differentiate into various T-cell subsets under strict regulation of miRNAs and transcription factors. Subsequently, the differentiation of B-cells from common lymphocyte progenitors in bone marrow and periphery were discussed in association with a network of miRNAs and transcription factors.
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    Development of pH and thermo-responsive smart niosomal carriers for delivery of gemcitabine to the breast cancer cells
    (Springernature, 2024) Ghalehshahi, Saeid Shirzadi; Saharkhiz, Shaghayegh; Naderi, Nazanin; Nasri, Negar; Saharkhiz, Shiva; Zarepour, Atefeh; Goodarzi, Reza
    The utilization of intelligent drug carriers in cancer therapy has emerged as a transformative paradigm in modern oncology. These advanced drug delivery systems exploit the distinctive characteristics of cancer cells and their surrounding microenvironment to attain precise and targeted drug release at the tumor site. In this study, we aim to introduce a novel niosome formulation endowed with dual-responsive properties, pH, and thermo-sensitivity, to enhance drug release precisely within the intended target site. Therefore, thin-film method was used for the fabrication of niosomes, incorporating dipalmitoylphosphatidylcholine (DPPC), as thermoresponsive phospholipid, and citraconic anhydride, as pH-responsive linker. The fabricated niosomes were evaluated through physicochemical analysis using Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Additionally, the entrapment efficiency (EE%) and drug release pattern of gemcitabine (GEM) were quantified at different conditions using UV-Visible spectroscopy. The bioactivity of these niosomes was also evaluated via cytotoxicity assay and flow cytometry. Results of physicochemical analysis verified the successful fabrication of spherical nanoparticles, with a size range of about 100-150 nm and a neutral surface charge. Furthermore, the fabricated niosomes showed sensitivity to acidic pH (6.5) and temperature exceeding the transition temperature (Tc) of the DPPC (41.5 degrees C). Importantly, the drug release profile indicated about 10-17% enhancement in drug release for the dual-stimuli platform in comparison to the single-stimuli ones. The cytotoxicity assay and flow cytometry analysis demonstrated an approximate 10% increase in cytotoxicity and about a 2.5-fold rise in apoptosis induction for the dual-stimuli responsive platform in contrast to the free drug. In conclusion, this dual-stimuli responsive nanocarrier presents a promising strategy to enhance the specificity and efficacy of cancer chemotherapy while simultaneously reducing the adverse side effects experienced by patients.
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    Empowering Cancer Therapy: Comparing PEGylated and Non-PEGylated Niosomes Loaded with Curcumin and Doxorubicin on MCF-7 Cell Line
    (Mdpi, 2023) Saharkhiz, Shaghayegh; Zarepour, Atefeh; Zarrabi, Ali
    Cancer remains an enduring challenge in modern society, prompting relentless pursuits to confront its complexities. However, resistance often emerges against conventional treatments, driven by their inherent limitations such as adverse effects and limited solubility. Herein, we spotlight a remarkable solution; a niosomal platform engineered to tandemly ferry two potent agents, doxorubicin (DOX) and curcumin (CUR). Notably, we delve into the pivotal role of PEGylation, unraveling its impact on therapeutic efficacy. These niosomes consist of Span 60, Tween 60, and cholesterol with a molar ratio of 5:2:3, which were prepared via a thin film hydration method. The physicochemical characterization of particles was performed using DLS, zeta potential measurement, SEM, and FTIR analysis. In addition, their encapsulation efficiency and release profile were determined using the HPLC method. Finally, their cytotoxicity and biocompatibility effects were checked by performing an MTT assay test on the MCF7 and L929 cell lines. The obtained results confirmed the successful fabrication of co-loaded niosomal structures with and without PEG coating. The fabricated nanoparticles had sizes in the range of 100 to 200 nm with a surface charge of about -18 mV for particles without PEG coating and -40 mV for coated particles. Notably, DOX encapsulation efficiency leaps from 20% to 62% in the transition from uncoated to coated, while CUR exhibits an impressive surge from 80% to 95%. The drug release was more controlled and slower in the coated sample. Finally, the MTT results confirmed the biocompatibility and synergistic effect of the simultaneous use of two drugs on cancer cells in the PEGylated niosomal particle. Based on the results, PEGylated niosomal particles can be considered adept vehicles for the simultaneous delivery of different chemotherapy cargoes with synergic interaction to overcome cancer.
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    Fabrication of a dual-drug-loaded smart niosome-g-chitosan polymeric platform for lung cancer treatment
    (MDPI, 2023) Zarepour, Atefeh; Eğil, Abdurrahim Can; Cokol Çakmak, Melike; Esmaeili Rad, Monireh; Çetin, Yüksel; Aydınlık, Şeyma; Zarrabi, Ali
    Changes in weather conditions and lifestyle lead to an annual increase in the amount of lung cancer, and therefore it is one of the three most common types of cancer, making it important to find an appropriate treatment method. This research aims to introduce a new smart nano-drug delivery system with antibacterial and anticancer capabilities that could be applied for the treatment of lung cancer. It is composed of a niosomal carrier containing curcumin as an anticancer drug and is coated with a chitosan polymeric shell, alongside Rose Bengal (RB) as a photosensitizer with an antibacterial feature. The characterization results confirmed the successful fabrication of lipid-polymeric carriers with a size of nearly 80 nm and encapsulation efficiency of about 97% and 98% for curcumin and RB, respectively. It had the Korsmeyer-Peppas release pattern model with pH and temperature responsivity so that nearly 60% and 35% of RB and curcumin were released at 37 degrees C and pH 5.5. Moreover, it showed nearly 50% toxicity against lung cancer cells over 72 h and antibacterial activity against Escherichia coli. Accordingly, this nanoformulation could be considered a candidate for the treatment of lung cancer; however, in vivo studies are needed for better confirmation.
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    Functionalized liposomes and niosomes for cancer therapy
    (Elsevier, 2024) Yavari, Maryam; Sarrami Foroushani, Elnaz; Nasri, Negar; Zarepour, Atefeh; Zarrabi, Ali; Mostafavi, Ebrahim
    Liposomes and niosomes are two members of lipid-based nanocarriers superfamily that have attracted lots of attention in the cancer therapy subject due to their interesting structural features. They are vesicular nanoparticles composed of cholesterol and phospholipid (liposomes) or surfactant (niosomes) that have the most similarity with cellular membranes and have the capability of loading both hydrophobic and hydrophilic therapeutic agents. Moreover, the surface of these carriers could be functionalized with different compounds to enhance their stability, bioavailability, and targeting ability, which finally could lead to improved therapeutic performance. This book chapter aims to discuss functionalized liposomal and niosomal therapeutic nanoparticles for cancer treatment. To this end, we will first describe different structural features of liposomes and niosomes and their different preparation methods. Then we will mention different generations of liposomes and niosomes as well as different types of functionalization that could affect the stability, loading capacity, and bioavailability of these carriers in targeted cancer tissue. © 2024 Elsevier Inc. All rights reserved.
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