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Öğe Precision Nanomedicine: Lapatinib-Loaded Chitosan-Gold Nanoparticles Targeting LINC01615 for Lung Cancer Therapy(Springer Science and Business Media Deutschland GmbH, 2025) Rezaei Aghdam, Hadi; Peymani, Maryam; Salehzadeh, Ali; Rouhi, Leila; Zarepour, Atefeh; Zarrabi, AliLong non-coding RNAs (lncRNAs) play essential roles as oncogenic factors in cancer progression by influencing cell proliferation, apoptosis, and metastasis pathways. This study aims to investigate the expression changes of LINC01615 in prevalent cancers, explore its correlation with patient mortality rates, and introduce a novel therapeutic approach to reduce LINC01615 expression. Using The Cancer Genome Atlas (TCGA) data, the expression changes of LINC01615 in various cancers were analyzed, and its relationship with patient survival rates through Cox regression analysis weas assessed. Co-expressed pathways related to LINC01615 were identified via network analysis. Potential drugs to decrease LINC01615 expression were identified using the GSE38376 study. Besides, chitosan-coated nanoparticles were fabricated and functionalized with the identified drug, Lapatinib, to examine their effect on lung cancer cell lines and changes in LINC01615 expression. Our results indicated elevated LINC01615 expression in various common cancers, particularly in lung cancer, which was associated with poor prognosis in lung, breast, and kidney cancers. Co-expression network analysis suggested links to metastasis-related genes. Lapatinib, identified through GEO data, was found to modulate LINC01615 expression effectively. Chitosan-gold nanoparticles conjugated with Lapatinib significantly reduced LINC01615 expression in lung cancer cell lines while enhancing apoptosis rates. Therefore, these nanoparticles could be considered a promising therapeutic candidate for treating cancers with overexpression of LINC01615. Graphical Abstract: (Figure presented.) © The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists 2024.Öğe Machine learning and experimental analyses identified miRNA expression models associated with metastatic osteosarcoma(Elsevier, 2024) Abedi, Samira; Behmanesh, Ali; Mazhar, Farid Najd; Bagherifard, Abolfazl; Sami, Sam Hajialiloo; Heidari, Negar; Hossein-Khannazer, Nikoo; Namazifard, Saina; Arki, Mandana Kazem; Shams, Roshanak; Zarrabi, Ali; Vosough, MassoudOsteosarcoma (OS), as the most common primary bone cancer, has a high invasiveness and metastatic potential, therefore, it has a poor prognosis. This study identified early diagnostic biomarkers using miRNA expression profiles associated with osteosarcoma metastasis. In the first step, we used RNA-seq and online microarray data from osteosarcoma tissues and cell lines to identify differentially expressed miRNAs. Then, using seven feature selection algorithms for ranking, the first-ranked miRNAs were selected as input for five machine learning systems. Using network analysis and machine learning algorithms, we developed new diagnostic models that successfully differentiated metastatic osteosarcoma from non-metastatic samples based on newly discovered miRNA signatures. The results showed that miR-34c-3p and miR-154-3p act as the most promising models in the diagnosis of metastatic osteosarcoma. Validation for this model by RT-qPCR in benign tissue and osteosarcoma biopsies confirmed the lower expression of miR-34c-3p and miR-154-3p in OS samples. In addition, a direct correlation between miR-34c-3p expression, miR-154-3p expression and tumor grade was discovered. The combined values of miR-34c-3p and miR-154-3p showed 90 % diagnostic power (AUC = 0.90) for osteosarcoma samples and 85 % (AUC = 0.85) for metastatic osteosarcoma. Adhesion junction and focal adhesion pathways, as well as epithelial-to-mesenchymal transition (EMT) GO terms, were identified as the most significant KEGG and GO terms for the top miRNAs. The findings of this study highlight the potential use of novel miRNA expression signatures for early detection of metastatic osteosarcoma. These findings may help in determining therapeutic approaches with a quantitative and faster method of metastasis detection and also be used in the development of targeted molecular therapy for this aggressive cancer. Further research is needed to confirm the clinical utility of miR-34c-3p and miR-154-3p as diagnostic biomarkers for metastatic osteosarcoma.Öğe Sustainable nanomaterials for precision medicine in cancer therapy(Elsevier, 2024) Bigham, Ashkan; Zarepour, Atefeh; Khosravi, Arezoo; Iravani, Siavash; Zarrabi, AliSustainable nanomaterials have attracted much attention in the last decades in different applications mainly to minimize harm to environment by using renewable resources. One of those areas is precision medicine for cancer therapy, offering tailored solutions for targeted drug delivery, cancer immunotherapy, imaging/biosensing, and therapy monitoring. Recent trends in bio- and nanomedicine have focused on developing biocompatible and biodegradable multifunctional nanocarriers that enhance drug delivery efficiency while minimize systemic toxicity. Fabricating sustainable nanomaterials with smart functionalities, such as stimuli-responsive behavior and targeted drug release mechanisms, holds great potential for improving the efficacy of therapy with more desirable outcomes. However, challenges persist in ensuring the biosafety, targeting efficiency, and specificity of these nanomaterials; also, clinical translation studies, optimizing scalability, and cost-effectiveness in production processes need to be addressed. The primary purpose of this review is to examine the recent advancements in sustainable nanomaterials for precision medicine in targeted cancer therapy via summarizing the progress made in this field. In addition, we mentioned about the crucial challenges related to these innovative solutions, such as ensuring the safety and sustainability of nanomaterials. Moreover, by exploring the future perspectives of this technology, we hope to provide insights into the direction of developments in sustainable nanomaterials for precision medicine, particularly in the context of targeted cancer therapy.Öğe Preparation and characterization of PBS (polybutylene succinate) nanoparticles containing cannabidiol (CBD) for anticancer application(Elsevier, 2024) Freire, Natalia Freitas; Cordani, Marco; Aparicio-Blanco, Juan; Sanchez, Ana Isabel Fraguas; Dutra, Luciana; Pinto, Martina C. C.; Zarrabi, Ali; Pinto, Jose Carlos; Velasco, Guillermo; Fialho, RosanaCannabidiol (CBD), a major constituent of Cannabis sativa, has demonstrated a broad range of therapeutic properties in human studies. Notably, CBD has shown anticancer activity in preclinical cancer models. However, its low water solubility poses challenges for bioavailability, necessitating the development of drug delivery systems to enhance its efficacy. This study aimed to create CBD-loaded Poly (butylene succinate) (PBS) nanoparticles and evaluate their effectiveness in in vitro cancer models. The nanoparticles, with an average size of 175 nm, were produced using a modified double emulsion/solvent evaporation technique. The release profile of CBD from the nanoparticles exhibited an initial rapid release followed by a slower sustained release. Cytotoxicity assays demonstrated that the CBD-PBS nanoparticles retained the anticancer effects of free CBD, selectively reducing the viability of cancer cell lines without affecting non -transformed fibroblasts. Additionally, the nanoformulation modulated key cellular pathways, as indicated by decreased AKT phosphorylation and increased LC3-II levels, suggesting that the encapsulated CBD preserved its ability to induce autophagy-mediated cell death in cancer cells. The nanoformulation also effectively inhibited cell migration in highly invasive prostate cancer cells, mirroring the effects of free CBD, while not impacting the migration of non -tumoral fibroblasts. These results underscore the therapeutic potential of this CBD nanoformulation, setting the stage for further in vivo investigations.Öğe The apoptotic effect of garlic (Allium sativum) derived SEVs on different types of cancer cell lines in vitro(Tubitak scientific & technological research council Turkey, 2024) Ünsal, Naz; Koçak, Polen; Yılmaz, Hazal; Şahin, Fikrettin; Canpolat, Merve YıldırımBackground/aim: Small extracellular vesicles (SEVs) are known to have an impact on the physiological conditions of target cells, are a critical component of cell -to -cell communication, and have been implicated in a variety of diseases. Although it has been proposed that edible plant -derived nanoparticles have an effect on communication with mammalian cells, the influence of these nanoparticles on cancer cell development has yet to be explored. Materials and methods: In order to characterize small extracellular vesicles obtained from garlic, specific SEV surface markers, antibodies, and size detections were identified using scanning electron microscopy and nanoparticle tracking analysis. Human hepatoma (Hep3B), human neuroblastoma (SH-SY5Y), human pancreatic adenocarcinoma (Panc-1a), human glioblastoma (U87), prostate cancer (PC -3), and human umbilical vein endothelial (HUVEC) cell lines were treated with garlic SEVs to examine their anticancer properties. Results: Annexin V FITC/PI staining for apoptosis, mRNA, and protein expression levels via RT-PCR and ELISA indicated that garlic SEVs triggered apoptosis by activating the intrinsic pathway. Our findings support the idea that SEVs produced from garlic may trigger apoptotic cell death in cancer cells while having no effect on healthy cells. Conclusion: It was discovered that plant SEVs had anti -cancer effects by activating caspase-mediated apoptosis.Öğe MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells(Elsevier B.V., 2024) Seydi, Homeyra; Nouri, Kosar; Shokouhian, Bahare; Piryaei, Abbas; Hassan, Moustapha; Cordani, Marco; Zarrabi, Ali; Shekari, Faezeh; Vosough, MassoudBackground: In spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both in vitro and in vivo. Method: Human Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated via RT-qPCR. Comprehensive in vitro and in vivo assessments were then performed on Huh-7 and HepG2 cell lines. Results: EV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators TFEB and ATG9A were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway. © 2024 Elsevier B.V.Öğe Amine-functionalized mesoporous silica nanoparticles decorated by silver nanoparticles for delivery of doxorubicin in breast and cervical cancer cells(Elsevier, 2024) Ghobadi, Melika; Salehi, Saeideh; Ardestani, Mohammad Taha Salmanifard; Mousavi-Khattat, Mohammad; Shakeran, Zahra; Khosravi, Arezoo; Cordani, Marco; Zarrabi, AliNanocarriers have demonstrated promising potential in the delivery of various anticancer drugs and in improving the efficiency of the treatment. In this study, silver nanoparticles (AgNPs) were green-synthesized using the extracts of different parts of the pomegranate plant, including the peel, flower petals, and calyx. To obtain the most efficient extract used for the green synthesis of AgNPs, all three types of synthesized nanoparticles were characterized. Then, (3-Aminopropyl) triethoxysilane-functionalized mesoporous silica nanoparticles (MSNs-APTES) decorated with AgNPs were fabricated via a one-pot green-synthesis method. AgNPs were directly coated on the surface of MSNs-APTES by adding pomegranate extract enriched with a source of reducing agent leading to converting the silver ion to AgNPs. The MSN-APTES-AgNPs (MSNs-AgNPs) have been thoroughly characterized using nanoparticle characterization techniques. In addition, DNA cleavage and hemolysis activities of the synthesized nanoparticles were analyzed, confirming the biocompatibility of synthesized nanoparticles. The Doxorubicin (DOX, as a breast/cervical anti-cancer drug) loading (42.8%) and release profiles were investigated via UV-visible spectroscopy. The fibroblast, breast cancer, and cervical cancer cells' viability against DOX-loaded nanoparticles were also studied. The results of this high drug loading, uniform shape, and small functionalized nanoparticles demonstrated its great potential for breast and cervical cancer management.Öğe Advancing personalized medicine: Integrating statistical algorithms with omics and nano-omics for enhanced diagnostic accuracy and treatment efficacy(Elsevier, 2024) Coşkun, Abdurrahman; Ertaylan, Gökhan; Pusparum, Murih; Van Hoof, Rebekka; Kaya, Zelal Zuhal; Khosravi, Arezoo; Zarrabi, AliMedical laboratory services enable precise measurement of thousands of biomolecules and have become an inseparable part of high-quality healthcare services, exerting a profound influence on global health outcomes. The integration of omics technologies into laboratory medicine has transformed healthcare, enabling personalized treatments and interventions based on individuals' distinct genetic and metabolic profiles. Interpreting laboratory data relies on reliable reference values. Presently, population-derived references are used for individuals, risking misinterpretation due to population heterogeneity, and leading to medical errors. Thus, personalized references are crucial for precise interpretation of individual laboratory results, and the interpretation of omics data should be based on individualized reference values. We reviewed recent advancements in personalized laboratory medicine, focusing on personalized omics, and discussed strategies for implementing personalized statistical approaches in omics technologies to improve global health and concluded that personalized statistical algorithms for interpretation of omics data have great potential to enhance global health. Finally, we demonstrated that the convergence of nanotechnology and omics sciences is transforming personalized laboratory medicine by providing unparalleled diagnostic precision and innovative therapeutic strategies.Öğe The apoptotic effect of garlic (Allium sativum) derived SEVs on different types of cancer cell lines in vitro(TÜBİTAK, 14.11.2024) Ünsal, Naz; Kocak, Polen; Yılmaz, Hazal; Şahin, Fikrettin; Yıldırım, MerveBackground/aim: Small extracellular vesicles (SEVs) are known to have an impact on the physiological conditions of target cells, are a critical component of cell-to-cell communication, and have been implicated in a variety of diseases. Although it has been proposed that edible plant-derived nanoparticles have an effect on communication with mammalian cells, the influence of these nanoparticles on cancer cell development has yet to be explored. Materials and methods: In order to characterize small extracellular vesicles obtained from garlic, specific SEV surface markers, antibodies, and size detections were identified using scanning electron microscopy and nanoparticle tracking analysis. Human hepatoma (Hep3B), human neuroblastoma (SH-SY5Y), human pancreatic adenocarcinoma (Panc-1a), human glioblastoma (U87), prostate cancer (PC-3), and human umbilical vein endothelial (HUVEC) cell lines were treated with garlic SEVs to examine their anticancer properties. Results: Annexin V FITC/PI staining for apoptosis, mRNA, and protein expression levels via RT-PCR and ELISA indicated that garlic SEVs triggered apoptosis by activating the intrinsic pathway. Our findings support the idea that SEVs produced from garlic may trigger apoptotic cell death in cancer cells while having no effect on healthy cells. Conclusion: It was discovered that plant SEVs had anti-cancer effects by activating caspase-mediated apoptosis.Öğe 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, AliRecently, 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.Öğe The therapeutic efficacy of 5-ALA based photodynamic therapy and chemotherapy combination in triple negative breast cancer cells(Springer, 2024) Erk, Beyzanur; Kamanlı, Ali Furkan; Eskiler, Gamze GüneyTriple negative breast cancer (TNBC) is one of the subtypes of breast cancer characterized by a heterogeneous and aggressive nature. Photodynamic therapy (PDT) has drawn significant attention in cancer treatment. However, solubility of photosensitizer, penetration problems into a target tissue and insufficient oxygen concentration limit the effectiveness of PDT. To overcome these limitations and to reduce the side effects of chemotherapy, combination treatment modalities play an essential role in cancer treatment. In this study, we aimed to investigate the combination efficacy of cisplatin-based chemotherapy and 5-Aminolevulinic acid (5-ALA)/PDT in TNBC cells and healthy breast cells in vitro. To determine the effect of the combination effects of cisplatin and 5-ALA/PDT on TNBC cells, two treatment protocols (simultaneous and sequential combination therapy) were evaluated compared with cisplatin and 5-ALA/PDT monotherapy and WST-1, Annexin V assay, acridine orange (AO) and mitochondrial staining were performed. Our findings showed that MDA-MB-231 TNBC cell viability was significantly decreased following simultaneous combination treatment compared to cisplatin and 5-ALA/PDT monotherapy. Additionally, simultaneous combination treatment was more effective than sequential combination treatment. The simultaneous combination treatment of 2.5 mu M cisplatin and 5-ALA/PDT at 6 J/cm2 and 9 J/cm2 induced 46.78% and 53.6% total apoptotic death, respectively in TNBC cells compared with monotherapies (cisplatin (37.88%) and 5-ALA/PDT (6 J/cm2: 31.48% and 9 J/cm2: 37.78%). Additionally, cisplatin and 5-ALA/PDT combination treatment resulted in nuclear fragmentation and mitochondrial damage due to apoptosis. Our results suggest that cisplatin and 5-ALA/PDT simultaneous combination therapy could be a promising new alternative strategy for treating TNBC. However, further studies are required to assess the underlying molecular mechanisms of cisplatin and 5-ALA/PDT combination treatment at the molecular level.Öğe 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, AliRecently, 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.Öğe Alginate-based nanocomposite incorporating chitosan nanoparticles: A dual-drug delivery system for infection control and wound regeneration(Editions de sante, 2025) Mousavi, Seyed Javad; Heydari, Parisa; Javaherchi, Pouya; Kharazi, Anoushe Zargar; Zarrabi, AliIn this study, a hydrogel-based nanocomposite was fabricated as a novel wound dressing and drug delivery system. Initially, insulin-loaded chitosan nanoparticles (CSNP-INS) were produced using the ionic gelation technique. Subsequently, the CSNP-INS were introduced into ciprofloxacin-loaded sodium alginate (SA-Cip) hydrogel at two different concentrations (0.5 % and 1 % w/v), followed by crosslinking with CaCl2 after freezedrying to enhance its physical and biological properties. The CSNP-INS nanoparticles had an average size of 173.6 f 1.76 nm and effectively encapsulated 70 % of the INS. Physicochemical characterization revealed that SA-Cip/1%CSNP-INS has significant swelling (2996 f 31.55 %) and high hydrophilicity (16.94 f 0.99 degrees), along with slow degradation due to the electrostatic interaction between CSNP and SA hydrogel (80 % weight loss after 14 days). Moreover, the mechanical properties were enhanced due to the higher concentration of CSNP (83 f 1.9 kPa), with a Young's modulus of 83 f 1.9 kPa. The release profile of INS after incorporation of CSNP-INS into the hydrogel was slower and more sustained. On the other hand, Cip showed a burst release (100 % within 6 h). In vitro assays of the fabricated hydrogels on fibroblastic cells demonstrated high cell viability, enhanced cell migration, and complete in-vitro wound closure (100 % within 24 h). Further analysis of the inflammatory response of hydrogels revealed a significant impact on modulating inflammation markers including a decrease in TNF-alpha and an increase in TGF-beta. Cip and INS facilitate different wound-healing stages, ensuring efficient and accelerated wound healing. This study underscores the potential of the developed hydrogel as groundbreaking wound dressing, offering enhanced wound healing capabilities through an innovative mechanism of controlled and sustained drug release.Öğe A novel microbial fuel cell design as biosensor to evaluate biochemical oxygen demand(Elsevier ltd, 2025) Naghibi, Negin; Khaleghi, Moj; Ataei, Seyed Ahmad; Zarrabi, AliMicrobial fuel cell (MFC) technology has gained significant attention for its dual capability to generate renewable energy and treat wastewater. Beyond these applications, MFCs have emerged as a promising tool for biosensing, particularly for detecting water pollutants. In this study, we aimed to optimize the evaluation of biochemical oxygen demand (BOD) by correlating it with the output voltage of an MFC. The effects of pH and external resistance on the MFC's performance were also assessed to enhance its operational stability. The experiment utilized a two-chambered MFC with a 2500 mL capacity, ceramic membrane, and carbon cloth electrodes. Synthetic wastewater and Shewanella xiamensis (code SH1 MF663195) were used as the anolyte, while distilled water served as the catholyte. Over 7 weeks, the MFC achieved a maximum current density of 1.939 mA/m2 and a power density of 80 mW/m2 at near-neutral pH and 3 k Omega external resistance. A positive linear correlation (R2 = 0.9984) was established between the output voltage and BOD concentration (16-436 mg/L). These findings suggest that this MFC-based biosensor is highly feasible and holds significant potential for real-time water quality monitoring.Öğe 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, AliWound 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.Öğe Synergistic enhancement of osteogenesis: silica nanoparticles and proanthocyanidin on bioinspired nanofibrous scaffolds for craniofacial bone regeneration(Springer Nature, 2024) Galefi, Atena; Hosseini, Saadi; Alipour, Atefeh; Banaeyan, Rezvaneh; Farrokhi, Naser; Amanzadeh, Amir; Wang, Peng-Yuan; Zarrabi, Ali; Shahsavarani, HoseinThe reconstruction of craniofacial bone defects is a significant challenge in regenerative medicine due to the limitations of standard grafts. In this study, we developed innovative, multifunctional, nanostructured scaffolds derived from Phlomis Monocephala leaves to address this issue. These fibrous cellulose scaffolds were coated with Grape Seed Proanthocyanidin Extract and Silica Nanoparticles, individually and in combination, to enhance their properties for bone tissue engineering applications. The scaffolds were meticulously evaluated for their morphology, chemical composition, swelling behavior, protein adsorption, hydrophilicity, porosity, and their ability to support cell survival, proliferation, and differentiation into bone cells. The scaffolds functionalized with both Grape Seed Proanthocyanidin Extract and Silica Nanoparticles exhibited the most favorable properties, significantly promoting the differentiation of human bone marrow mesenchymal stem cells into osteogenic cells. This was evidenced by increased alkaline phosphatase activity, matrix mineralization, collagen formation, and the expression of genes related to bone formation. Additionally, these nanostructured scaffolds demonstrated superior antibacterial activity against both Gram-positive and Gram-negative bacteria compared to uncoated scaffolds. In vivo biocompatibility assessments revealed that the Grape Seed Proanthocyanidin Extract and Silica Nanoparticles-coated scaffolds performed excellently in terms of re-epithelialization, vascularization, and reducing inflammation, showcasing their potential for future clinical applications. Our findings highlight the immense potential of these nanostructured scaffolds as biocompatible materials for treating bone tissue defects, offering a novel and effective approach in the field of nanotechnology and regenerative medicine. © Qatar University and Springer Nature Switzerland AG 2024.Öğe The role of glycolysis in tumorigenesis: from biological aspects to therapeutic opportunities(Elsevier inc., 2024) Cordani, Marco; Michetti, Federica; Zarrabi, Ali; Zarepour, Atefeh; Rumio, Cristiano; Strippoli, Raffaele; Marcucci, FabrizioGlycolytic metabolism generates energy and intermediates for biomass production. Tumor-associated glycolysis is upregulated compared to normal tissues in response to tumor cell-autonomous or non-autonomous stimuli. The consequences of this upregulation are twofold. First, the metabolic effects of glycolysis become predominant over those mediated by oxidative metabolism. Second, overexpressed components of the glycolytic pathway (i.e. enzymes or metabolites) acquire new functions unrelated to their metabolic effects and which are referred to as "moonlighting" functions. These functions include induction of mutations and other tumor-initiating events, effects on cancer stem cells, induction of increased expression and/or activity of oncoproteins, epigenetic and transcriptional modifications, bypassing of senescence and induction of proliferation, promotion of DNA damage repair and prevention of DNA damage, antiapoptotic effects, inhibition of drug influx or increase of drug efflux. Upregulated metabolic functions and acquisition of new, non-metabolic functions lead to biological effects that support tumorigenesis: promotion of tumor initiation, stimulation of tumor cell proliferation and primary tumor growth, induction of epithelial-mesenchymal transition, autophagy and metastasis, immunosuppressive effects, induction of drug resistance and effects on tumor accessory cells. These effects have negative consequences on the prognosis of tumor patients. On these grounds, it does not come to surprise that tumor-associated glycolysis has become a target of interest in antitumor drug discovery. So far, however, clinical results with glycolysis inhibitors have fallen short of expectations. In this review we propose approaches that may allow to bypass some of the difficulties that have been encountered so far with the therapeutic use of glycolysis inhibitors.Öğe Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer(Elsevier Masson s.r.l., 2024) Esmaeili, Y.; Dabiri, A.; Mashayekhi, F.; Rahimmanesh, I.; Bidram, E.; Karbasi, S.; Rafienia M.This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies. © 2024 Isfahan university of meeical sciencesÖğe MXene/zeolitic imidazolate framework (ZIF) composites: A perspective on their emerging applications(Elsevier B.V., 2024) Iravani, S.; Zare, E.N.; Zarrabi, A.; Khosravi, A.; Makvandi, P.MXene/zeolitic imidazolate framework (ZIF) composites represent a rapidly growing area of research in the field of energy storage, catalysis, sensing, flexible electronics, microwave/electromagnetic wave absorption, biomedicine, and environmental remediation/water treatment. The integration of MXene and ZIFs in composite materials has led to develop highly sensitive and selective (bio)sensing platforms, enabling advances in biomedicine/healthcare, environmental monitoring, and industrial safety. MXene/ZIF composites showcase exceptional catalytic activity for a wide range of chemical transformations. Their exceptional adsorption capacity, selectivity, membrane integration, regeneration capabilities, and antibacterial properties make them invaluable assets in tackling water treatment challenges. The combination of MXene's conductivity and ZIF's dielectric properties, along with their unique morphological features, results in enhanced microwave absorption capabilities. Furthermore, while the biomedical applications of MXene/ZIF composites are still in the early stages of exploration, the combination of their unique properties provides a platform for innovative solutions in drug delivery, cancer nanotheranostics, bioimaging, tissue engineering, and biosensing. This article aims to present a comprehensive overview of the research progress in MXene/ZIF composites, focusing on current trends, important challenges, and future perspectives. © 2024 Elsevier B.V.Öğe Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies(NLM (Medline), 2023) Esmaeili, Yasaman; Mohammadi, Zahra; Khavani, Mohammad; Sanati, Alireza; Shariati, Laleh; Seyedhosseini Ghaheh, Hooria; Bidram, Elham; Zarrabi, AliIntegrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
