Barbed Wire Around Science: The Politicization of Knowledge 2 2 No Abstract 233 233 Shahin Akhondzadeh Editorial 70632.pdf Akhondzadeh S. US Editors and Reviewers can no Longer Handle Submissions by Authors Employed by the Government of Iran: Is it Fair and Logical? Avicenna J Med Biotechnol 2013;5(4):203.##Akhondzadeh S. Iran's scientists uncrushed by decades of sanctions. Nature 2018;559(7714):331.##Akhondzadeh S. Possibility for science without borders in the Trump era. Lancet 2019;393(10170):405-406.##

The Synergy Between Mitochondrial Function and Innate Heat in Traditional Persian Medicine: A Modern Scientific Perspective on Thermoregulation 2 2 This study investigates the synergy between Traditional Persian Medicine (TPM)'s concept of innate heat (Hararat-e-Gharizi) and modern mitochondrial thermoregulation. TPM emphasizes innate heat as essential for sustaining life, paralleling modern understandings of mitochondrial ATP production and heat generation. This integration occurs through mitochondrial biogenesis, proton leak (via uncoupling proteins), and Reactive Oxygen Species (ROS) signaling, which correspond to the TPM concept of heat sustaining vital functions. These findings may guide novel therapeutic strategies that integrate TPM principles with mitochondrial biology. A comprehensive review of historical TPM texts and modern literature was conducted, comparing innate heat with mitochondrial roles in thermoregulation and energy balance. Data from PubMed, Google Scholar, and Scopus were analyzed to explore mechanisms of heat production in both traditional and modern contexts. Findings demonstrated that TPM's innate heat correlates with mitochondrial biogenesis, heat generation via Uncoupling Proteins (UCP1), and ROS regulation. These concepts reflect TPM’s understanding of maintaining bodily warmth for health and longevity. The relationship between Hararat-e-Gharizi and mitochondrial thermogenesis offers a bridge between ancient medicinal practices and modern cellular biology. Both emphasize the role of heat in maintaining homeostasis and preventing disease, with modern science validating TPM's holistic approach. Clarifying these mechanisms provides deeper insight into therapeutic implications, highlighting thermodynamic parallels and the role of ROS signaling as a novel framework for understanding disease etiology and treatment. This study bridges Traditional Persian Medicine and modern mitochondrial thermoregulation, introducing integrative perspectives for personalized healthcare. It also highlights thermodynamic parallels and ROS signaling as a novel framework for understanding disease etiology and treatment. This study underscores the relevance of TPM’s innate heat in modern medicine, emphasizing the importance of mitochondrial efficiency in thermoregulation and overall health. Integrating these perspectives can enhance personalized therapeutic strategies for disease prevention and longevity. 234 241 Majid Nimrouzi Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences Iran Masoud Hashemzaei BiologyBiomedical technologyBody temperature regulationHot temperatureLiteratureMitochondrial uncoupling proteins 70624.pdf Milota MM, Van Thiel GJ, Van Delden JJ. Narrative medicine as a medical education tool: a systematic review. Med Teach 2019;41(7):802–10##Talebi S, Emadi F, Ghaffari F, Jorjani M, Naseri M. A review of the relationship between the heart function and cardiotonic strategies for the prevention of depression from the Avicenna’s perspective. Journal of Islamic and Iranian Traditional Medicine 2020;10(4):309–22.##Moradi Dehnavi H, Roshan H, Hosseini SE. The effect of nutrition on maintaining the health of heart, brain, and liver from the perspective of traditional Persian medicine. Journal of Islamic and Iranian Traditional Medicine 2021;11(4):331–44.##Vaghasloo MA, Naghizadeh A, Babashahi N. The Concept of the Haar-re-Gharizi and Hararate Gharizi: The innate hot [Substance] and heat. Traditional and Integrative Medicine 2017:3–8.##West JB. Galen and the beginnings of Western physiology. Am J Physiol Lung Cell Mol Physiol 2014;307(2):L121–L8##Shirbeigi L, Zarei A, Naghizadeh A, Vaghasloo MA. The concept of temperaments in traditional Persian medicine. Traditional and Integrative Medicine 2017:143–56.##Tansaz M, Akhtari M, Naseri M, Majdzadeh R, Isfeedvajani MS, Shams-Ardakani MR, et al. Relationship between anthropometric indices and Mizaj (temperament) in Persian medicine. Caspian J Intern Med 2023;14(2):205##Panossian AG, Efferth T, Shikov AN, Pozharitskaya ON, Kuchta K, Mukherjee PK, et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐and aging‐related diseases. Med Res Rev 2021;41(1):630–703. ##Kamshilin AA, Zaytsev VV, Belaventseva AV, Podolyan NP, Volynsky MA, Sakovskaia AV, et al. Novel Method to Assess Endothelial Function via Monitoring of Perfusion Response to Local Heating by Imaging Photoplethysmography. Sensors (Basel) 2022;22(15):5727. ##Singh IS, Hasday JD. Fever, hyperthermia and the heat shock response. Int J Hyperthermia 2013 Aug;29(5):423-35.##Nimrouzi M, Mahbodi A, Jaladat AM, Sadeghfard A, Zarshenas MM. Hijamat in traditional Persian medicine: risks and benefits. J Evid Based Complementary Altern Med 2014;19(2):128–36. ##Ramin F. The Definition of Life and Death from the View of Avicenna and Modern Medicine. Curr Probl Cardiol 2024:102424. ##Singla A. Precision medicine: Tailoring treatment to indi-vidual genetic profiles. Journal for Medical Research Ad-vancement 2024;1(1).##Cramer MN, Gagnon D, Laitano O, Crandall CG. Human temperature regulation under heat stress in health, disease, and injury. Physiol Rev 2022 Oct 1;102(4):1907-1989. ##Osilla EV, Marsidi JL, Shumway KR, Sharma S. Physiology, Temperature Regulation. 2023 Jul 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan.##Weber L. Western Political Thought: Scientific e-Resources; 2018.##Rothhaas R, Chung S. Role of the preoptic area in sleep and thermoregulation. Front Neurosci 2021;15:664781. ##Biro GP. Oxygen and ATP: the Energy Economy of the Cell. InBlood substitutes and oxygen biotherapeutics 2022 Aug 9 (pp. 21-32). Cham: Springer International Publishing.##Beignon F, Gueguen N, Tricoire-Leignel H, Mattei C, Lenaers G. The multiple facets of mitochondrial regulations controlling cellular thermogenesis. Cell Mol Life Sci 2022;79(10):525. ##Ghaffari F, Taheri M, Meyari A, Karimi Y, Naseri M. Avicenna and clinical experiences in Canon of Medicine. J Med Life 2022;15(2):168. ##Moradi F, Alizadeh F, Naghizadeh A, Karimi M, Vaghasloo MA. The concept of “Masam”(Pores) in Persian medicine. Traditional and Integrative Medicine 2017:160–5.##Nimrouzi M, Daneshfard B, Tafazoli V. The Concept of Porosity and Condensity in Persian Medicine. Journal of Research on History of Medicine 2022;11(2):105–14.##Nimrouzi M, Bemani M, Zare M, Zazerani S, Soltanabadi N, Fathi M, et al. [Role of body temperature on health: traditional and conventional]. Tārīkh-i pizishkī 2014;6(19):29–44. Persian.##Ghorbani F, Keshavarz M, Nazem E, Imani AR, Faghihi M. Overall meaning of cardiotonic and its mechanisms of action from the viewpoint of Iranian traditional medicine. Journal of Islamic and Iranian Traditional Medicine 2014;5(3):196–204.##Nimrouzi M, Shahroodi AS, Sharifi MH, Daneshfard B. Conceptual Relationship Between Traditional Persian Medicine and Modern Nutrition in Obesity in Middle Age 2021.##Kamaneh S, Mojahedi M, Mozafari O, Memariani Z, Saravani M. Cardiotonic Medicines (Mofarrehs) and Their Mechanism of Action in Persian Medicine. Journal of Babol University of Medical Sciences 2019;21(1):320–30.##Morrison SF, Nakamura K. Central neural pathways for thermoregulation. Front Biosci (Landmark Ed 2011;16:74. ##Mowery NT, Morris Jr JA, Jenkins JM, Ozdas A, Norris PR. Core temperature variation is associated with heart rate variability independent of cardiac index: a study of 278 trauma patients. J Crit Care 2011;26(5):534. e9–e17. ##Evans SS, Repasky EA, Fisher DT. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol 2015;15(6):335–49. ##Chauhan NR, Kapoor M, Singh LP, Gupta RK, Meena RC, Tulsawani R, et al. Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation. Neuroscience 2017;358:79–92. ##Jackson M. The Routledge history of disease: Routledge London/New York; 2017.##Itrat M, Zulkifle M. A temperamental approach in promotion of health. Medical Journal of Islamic World Academy of Sciences 2014;109(1566):1–5.##Ortega SP, Chouchani ET, Boudina S. Stress turns on the heat: Regulation of mitochondrial biogenesis and UCP1 by ROS in adipocytes. Adipocyte 2017;6(1):56–61. ##Roberts RC. Mitochondrial dysfunction in schizophrenia: with a focus on postmortem studies. Mitochondrion 2021;56:91–101.##Jamerson LE, Bradshaw PC. The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity. Antioxidants (Basel) 2024;13(7):820. ##Xu X, Lian Z. Which physiological measurements can characterize core and surface body temperature? A case study in stable thermal environment. Building and Environment 2024;247:111019.##Bartoš H, King CG. Heat, Pneuma, and Soul in Ancient Philosophy and Science: Cambridge University Press; 2020.##Schirrmacher V. Mitochondria at work: new insights into regulation and dysregulation of cellular energy supply and metabolism. Biomedicines 2020;8(11):526. ##Brekhman IIsk. Man and biologically active substances: the effect of drugs, diet and pollution on health: Elsevier; 2013.##Altieri DC. Mitochondrial dynamics and metastasis. Cell Mol Life Sci 2019;76:827–35. ##Kruglov AG, Romshin AM, Nikiforova AB, Plotnikova A, Vlasov II. Warm cells, hot mitochondria: achievements and problems of ultralocal thermometry. Int J Mol Sci 2023;24(23):16955. ##Ruan L, Chen J, Du C, Lu H, Zhang J, Cai X, et al. Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer. Bioact Mater 2022;13:191–9. ##Li X, Song S, Shuai Q, Pei Y, Aastrup T, Pei Y, et al. Real-time and label-free analysis of binding thermodynamics of carbohydrate-protein interactions on unfixed cancer cell surfaces using a QCM biosensor. Sci Rep 2015;5(1):1–9. ##Münch C, Harper JW. Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation. Nature 2016;534(7609):710–3. ##Arranz-Paraíso D, Sola Y, Baeza-Moyano D, Benitez-Martinez M, Melero-Tur S, González-Lezcano RA. Mitochondria and light: An overview of the pathways triggered in skin and retina with incident infrared radiation. J Photochem Photobiol B 2023;238:112614. ##Kang Y, Kong N, Ou M, Wang Y, Xiao Q, Mei L, et al. A novel cascaded energy conversion system inducing efficient and precise cancer therapy. Bioact Mater 2023;20:663–76. ##Lucia U. Irreversibility in biophysical and biochemical engineering. Physica A: Statistical Mechanics and its Applications. 2012;391(23):5997–6007.##Ashraf G, Chen W, Asif M, Aziz A, Zhong ZT, Iftikhar T, et al. Topical advancements in electrochemical and opti-cal signal amplification for biomolecules detection: A comparison. Materials Today Chemistry 2022;26: 1011.19.##Akhtari M, Moeini R, Mojahedi M, Gorji N. Assessment the studies on the concept of Mizaj (temperament) in Persian Medicine. J Complement Integr Med 2020;17(3):20180122. ##Manera M. Perspectives on Complexity, Chaos and Thermodynamics in Environmental Pathology. Int J Environ Res Public Health 2021;18(11):5766. ##Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science 2011;331(6024):1559–64. ##Wang S, Fu B, Zhao W, Liu Y, Wei F. Structure, function, and dynamic mechanisms of coupled human–natural systems. Current Opinion in Environmental Sustainability 2018;33:87–91.##El-Gammal Z, Nasr MA, Elmehrath AO, Salah RA, Saad SM, El-Badri N. Regulation of mitochondrial temperature in health and disease. Pflugers Arch 2022;474(10):1043–51.##Chrétien D, Bénit P, Ha HH, Keipert S, El-Khoury R, Chang YT, et al. Mitochondria are physiologically maintained at close to 50 C. PLoS Biol 2018;16(1):e2003992.##

Challenges and Future Prospects of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in Nanomedicine: A Focus on Toxicity, Imaging, and Theranostics 2 2 Superparamagnetic Iron Oxide Nanoparticles (SPIO Ns) have emerged as a pivotal tool in nanomedicine, offering potential in drug delivery, imaging, and targeted therapies. However, their application is challenged by issues such as cytotoxicity, uneven biodistribution, and biocompatibility. SPIONs are predominantly cleared through renal or hepatobiliary pathways, with size and charge playing critical roles in determining their fate. While smaller SPIONs optimize renal clearance, their propensity to agglomerate and activate macrophages may induce inflammatory responses. Radiolabeled SPIONs face additional challenges in molecular imaging and nuclear medicine. Emerging strategies, such as chelator-free radiolabeling and multi-component nanoparticles, aim to address these limitations by improving targeting specificity and enhancing biocompatibility. Looking forward, SPIONs hold immense potential in theranostics, particularly in integrating imaging with targeted drug delivery and therapies. Advances in synthesis and surface functionalization may enhance their safety and effectiveness. Future research should focus on optimizing SPIONs, integrating them with therapeutic agents, and improving targeting and clearance mechanisms. Collaboration among experts and the use of Artificial Intelligence (AI) modeling could accelerate their development for personalized treatment applications. This review uniquely highlights recent advances in radiolabeled SPIONs for molecular imaging and targeted therapy, addressing challenges like biocompatibility, stability, and translational applicability. 242 248 Maryam Alvandi Cardiovascular Research Center, Hamadan University of Medical SciencesDepartment of Nuclear Medicine and Molecular Imaging, School of Medicine, Hamadan University of Medical Sciences Cardiovascular Research Center, Hamadan University of Medical SciencesDepartment of Nuclear Medicine and Molecular Imaging, School of Medicine, Hamadan University of Medical Sciences IranIran Sahar Nosrati Institute of Nuclear Chemistry and Technology, Dorodna 16 Str, 03-195 Institute of Nuclear Chemistry and Technology, Dorodna 16 Str, 03-195 Poland Ramin Mansouri Student Research Committee, Hamadan University of Medical Sciences Student Research Committee, Hamadan University of Medical Sciences Iran Zahra Shaghaghi Shahnaz Saednia Farabi Hospital, Isfahan University of Medical Sciences Farabi Hospital, Isfahan University of Medical Sciences Iran Sara Alipour Student Research Committee, Hamadan University of Medical Sciences Student Research Committee, Hamadan University of Medical Sciences Iran Farzad Fathi Student Research Committee, Hamadan University of Medical Sciences Student Research Committee, Hamadan University of Medical Sciences Iran Molecular imagingPET/MRIRadiolabelingSuperparamagnetic Iron Oxide NanoparticlesToxicity 70625.pdf Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71(3):209-49.##Bakhtiary Z, Saei AA, Hajipour MJ, Raoufi M, Vermesh O, Mahmoudi M. Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges. Nanomedicine 2016;12(2):287-307.##Farzin L, Sheibani S, Moassesi ME, Shamsipur M. An overview of nanoscale radionuclides and radiolabeled nanomaterials commonly used for nuclear molecular imaging and therapeutic functions. J Biomed Mater Res A 2019;107(1):251-85.##Ma YY, Jin KT, Wang SB, Wang HJ, Tong XM, Huang DS, Mou XZ. Molecular imaging of cancer with nanoparticle‐based theranostic probes. Contrast Media Mol Imaging 2017;2017(1):1026270.##Alvandi M, Shaghaghi Z, Aryafar V, Fariba F, Sanaei Z. The evaluation of left ventricular dyssynchrony in hypertensive patients with a preserved systolic function undergoing gated SPECT myocardial perfusion imaging. Ann Nucl Med 2019;33(12):899-906.##Shaghaghi Z, Mansouri R, Nosrati S, Alvandi M. Multimodal imaging in cancer detection: the role of SPIONs and USPIONs as contrast agents for MRI, SPECT, and PET. Future Oncol 2025;21(18):2367-83.##Mukherjee S, Liang L, Veiseh O. Recent advancements of magnetic nanomaterials in cancer therapy. Pharmaceutics 2020;12(2):147.##Racca L, Cauda V. Remotely activated nanoparticles for anticancer therapy. Nanomicro Lett 2021;13:11.##Naz S, Shamoon M, Wang R, Zhang L, Zhou J, Chen J. Advances in therapeutic implications of inorganic drug delivery nano-platforms for cancer. Int J Mol Sci 2019;20(4):965.##Wenzel D. Magnetic nanoparticles: novel options for vascular repair? Nanomedicine (Lond) 2016 Apr;11(8):869-72.##Garcia J, Tang T, Louie AY. Nanoparticle-based multimodal PET/MRI probes. Nanomedicine (Lond) 2015;10(8):1343-59.##Aziz OAA, Arafa K, Dena ASA, El-Sherbiny IM. Superparamagnetic iron oxide nanoparticles (SPIONs): preparation and recent applications. J Nanotech Adv Mat 2020;8:21-9.##Li L, Jiang W, Luo K, Song H, Lan F, Wu Y, Gu Z. Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking. Theranostics 2013;3(8):595-615.##Stockhofe K, Gimnich M, Klinker K, Roesch F, Barz M, Ross TL. Radiolabeling of cross-linked polymer micelles with 68Ga for PET-imaging. Society of Nuclear Medicine; 2016.##Adamiano A, Iafisco M, Sandri M, Basini M, Arosio P, Canu T, et al. On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging. Acta Biomater 2018;73:458-69.##Psimadas D, Baldi G, Ravagli C, Bouziotis P, Xanthopoulos S, Franchini MC, et al. Preliminary evaluation of a 99mTc labeled hybrid nanoparticle bearing a cobalt ferrite core: in vivo biodistribution. J Biomed Nanotechnol 2012;8(4):575-85.##Ansari MO, Ahmad MF, Shadab G, Siddique HR. Superparamagnetic iron oxide nanoparticles based cancer theranostics: A double edge sword to fight against cancer. Journal of Drug Delivery Science and Technology 2018;45:177-83.##Singh N, Jenkins GJ, Asadi R, Doak SH. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev 2010;1(1):5358.##Lamichhane N, Sharifabad ME, Hodgson B, Mercer T, Sen T. Superparamagnetic iron oxide nanoparticles (SPIONs) as therapeutic and diagnostic agents. Nanoparticle therapeutics: Elsevier; 2022. p. 455-97.##Zhang L, Jin R, Sun R, Du L, Liu L, Zhang K, et al. Superparamagnetic iron oxide nanoparticles as magnetic resonance imaging contrast agents and induced autophage response endothelial progenitor cells. J Biomed Nanotechnol 2019 Feb 1;15(2):396-404.##Sodipo BK, Aziz AA. Recent advances in synthesis and surface modification of superparamagnetic iron oxide nanoparticles with silica. Journal of Magnetism and Magnetic Materials 2016;416:275-91.##de Souza Albernaz M, Toma SH, Clanton J, Araki K, Santos-Oliveira R. Decorated superparamagnetic iron oxide nanoparticles with monoclonal antibody and diethylene-triamine-pentaacetic acid labeled with thechnetium-99m and galium-68 for breast cancer imaging. Pharm Res 2018;35(1):24.##Goel S, England CG, Chen F, Cai W. Positron emission tomography and nanotechnology: A dynamic duo for cancer theranostics. Adv Drug Deliv Rev 2017;113:157-76.##Shanehsazzadeh S, Grüttner C, Yousefnia H, Lahooti A, Gholami A, Nosrati S, et al. Development of 177Lu-DTPA-SPIO conjugates for potential use as a dual contrast SPECT/MRI imaging agent. Radiochimica Acta 2016;104(5):337-44.##Polo E, del Pino P, Pardo A, Taboada P, Pelaz B. Magnetic nanoparticles for cancer therapy and bioimaging. InNanooncology: Engineering nanomaterials for cancer therapy and diagnosis 2018 Jun 2 (pp. 239-279). Cham: Springer International Publishing.##Wu W, Wu Z, Yu T, Jiang C, Kim W-S. Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications. Sci Technol Adv Mater 2015;16(2):023501.##Ittrich H, Peldschus K, Raabe N, Kaul M, Adam G, editors. Superparamagnetic iron oxide nanoparticles in biomedicine: applications and developments in diagnostics and therapy. Rofo 2013 Dec;185(12):1149-66.##Madru R, Svenmarker P, Ingvar C, Ståhlberg F, Engels S-A, Knutsson L, Strand S-E. Development of a hybrid nanoprobe for triple-modality MR/SPECT/optical fluorescence imaging. Diagnostics (Basel) 2014;4(1):13-26.##Wang G, Xie H, Hou S, Chen W, Yang X. Development of high‐field permanent magnetic circuits for NMRI/MRI and imaging on mice. Biomed Res Int 2016;2016(1):8659298.##Javed Y, Akhtar K, Anwar H, Jamil Y. MRI based on iron oxide nanoparticles contrast agents: effect of oxidation state and architecture. Journal of Nanoparticle Research 2017;19:366.##Huang J, Zhong X, Wang L, Yang L, Mao H. Improving the magnetic resonance imaging contrast and detection methods with engineered magnetic nanoparticles. Theranostics 2012;2(1):86-102.##Lurie DJ. Basic MRI physics for radiotherapy physicists. Physica Medica 2016;32:175.##Si G, Du Y, Tang P, Ma G, Jia Z, Zhou X, et al. Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI. Natl Sci Rev 2024;11(5):nwae057.##Eghbali P, Fattahi H, Laurent S, Muller RN, Oskoei YM. Fluorophore-tagged superparamagnetic iron oxide nanoparticles as bimodal contrast agents for MR/optical imaging. Journal of the Iranian Chemical Society 2016;13:87-93.##Huang J, Qian W, Wang L, Wu H, Zhou H, Wang AY, et al. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer. Int J Nanomedicine 2016:3087-99.##Amiri H, Saeidi K, Borhani P, Manafirad A, Ghavami M, Zerbi V. Alzheimer’s disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents. ACS Chem Neurosci 2013;4(11):1417-29.##Frantellizzi V, Conte M, Pontico M, Pani A, Pani R, De Vincentis G. New frontiers in molecular imaging with superparamagnetic iron oxide nanoparticles (SPIONs): efficacy, toxicity, and future applications. Nucl Med Mol Imaging 2020;54:65-80.##Wang Y, Ye F, Jeong EK, Sun Y, Parker DL, Lu ZR. Noninvasive visualization of pharmacokinetics, biodistribution and tumor targeting of poly [N-(2-hydroxypropyl) methacrylamide] in mice using contrast enhanced MRI. Pharmaceutical Research 2007;24:1208-16.##Donaldson K, Schinwald A, Murphy F, Cho WS, Duffin R, Tran L, Poland C. The biologically effective dose in inhalation nanotoxicology. Acc Chem Res 2013;46(3):723-32. ##Galaris D, Pantopoulos K. Oxidative stress and iron homeostasis: mechanistic and health aspects. Crit Rev Clin Lab Sci 2008;45(1):1-23.##Halliwell B, Gutteridge JM. Free radicals in biology and medicine: Oxford university press; 2015.##Collard KJ. Iron homeostasis in the neonate. Pediatrics 2009;123(4):1208-16.##Kornberg TG, Stueckle TA, Antonini JM, Rojanasakul Y, Castranova V, Yang Y, Rojanasakul LW. Potential toxicity and underlying mechanisms associated with pulmonary exposure to iron oxide nanoparticles: conflicting literature and unclear risk. Nanomaterials 2017;7(10):307.##Malvindi MA, De Matteis V, Galeone A, Brunetti V, Anyfantis GC, Athanassiou A, et al. Toxicity assessment of silica coated iron oxide nanoparticles and biocompatibility improvement by surface engineering. PloS One 2014;9(1):e85835.##Reddy UA, Prabhakar P, Mahboob M. Biomarkers of oxidative stress for in vivo assessment of toxicological effects of iron oxide nanoparticles. Saudi J Biol Sci 2017;24(6):1172-80.##Park EJ, Umh HN, Choi DH, Cho MH, Choi W, Kim SW, et al. Magnetite-and maghemite-induced different toxicity in murine alveolar macrophage cells. Arch Toxicol 2014;88:1607-18.##Lee JH, Ju JE, Kim BI, Pak PJ, Choi EK, Lee HS, Chung N. Rod‐shaped iron oxide nanoparticles are more toxic than sphere‐shaped nanoparticles to murine macrophage cells. Environ Toxicol Chem 2014;33(12):2759-66.##Shaghaghi Z, Nosrati S, Mansouri R, Alvandi M. Advances and Challenges in the Application of Radiolabeled Magnetic Nanoparticles for Cancer Theranostics. Nucl Med Mol Imaging 2025;59(5):315-28.##Bhattacharya K, Davoren M, Boertz J, Schins RP, Hoffmann E, Dopp E. Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 2009;6:1-11.##Chen Z, Yin JJ, Zhou YT, Zhang Y, Song L, Song M, et al. Dual enzyme-like activities of iron oxide nanoparticles and their implication for diminishing cytotoxicity. ACS Nano 2012;6(5):4001-12.##Longmire M, Choyke PL, Kobayashi H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine 2008;3(5):703-17.##Nelson NR, Port JD, Pandey MK. Use of superparamagnetic iron oxide nanoparticles (SPIONs) via multiple imaging modalities and modifications to reduce cytotoxicity: An educational review. Journal of Nanotheranostics 2020;1(1):105-35.##Soo Choi H, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, et al. Renal clearance of quantum dots. Nat Biotechnol 2007;25(10):1165-70.##Stolnik S, Illum L, Davis S. Long circulating microparticulate drug carriers. Advanced Drug Delivery Reviews 2012;64:290-301.##Mirshafiee V, Sun B, Chang CH, Liao YP, Jiang W, Jiang J, et al. Toxicological Profiling of Metal Oxide Nanoparticles in Liver Context Reveals Pyroptosis in Kupffer Cells and Macrophages versus Apoptosis in Hepatocytes. ACS Nano 2018 Apr 24;12(4):3836-3852.##Lapusan R, Borlan R, Focsan M. Advancing MRI with magnetic nanoparticles: a comprehensive review of translational research and clinical trials. Nanoscale Adv Apr 2;6(9):2234-59.##Azadbakht B, Afarideh H, Ghannadi-Maragheh M, Bahrami-Samani A, Asgari M. Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab. Nucl Med Biol 2017;48:26-30.##Hajiramezanali M, Atyabi F, Mosayebnia M, Akhlaghi M, Geramifar P, Jalilian AR, et al. 68Ga-radiolabeled bombesin-conjugated to trimethyl chitosan-coated superparamagnetic nanoparticles for molecular imaging: preparation, characterization and biological evaluation. Int J Nanomedicine 2019:2591-605.##García-Fernández J, de la Fuente Freire M. Exosome-like systems: nanotechnology to overcome challenges for targeted cancer therapies. Cancer Lett 2023;561:216151.##

Antiplasmodial Activity of Green-Synthesized MgO Nanoparticles Using Achillea millefolium Against Chloroquine-Resistant and-Sensitive Plasmodium falciparum 2 2 Background: Resistance to antimalarial medications, particularly in Plasmodium falciparum (P. falciparum), has emerged as a significant challenge, highlighting the need for innovative therapeutic strategies. Green-synthesized magnesium oxide nanoparticles (MgO NPs) represent a promising approach to therapeutic interventions. This study presents one of the first detailed evaluations of green-synthesized MgO NPs derived from Achillea millefolium (A. millefolium) against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) P. falciparum strains. Methods: In this study, MgO NPs were biosynthesized using A. millefolium extracts with varying solvent ratios. The nanoparticles were characterized using UV-Vis, FTIR, FESEM, and DLS techniques. Cytotoxicity was assessed via MTT and hemolysis assays. Their antiplasmodial efficacy was evaluated in vitro against chloroquine-sensitive (3D7) and -resistant (K1) P. falciparum strains. Results: The synthesized MgO NPs displayed quasi-spherical morphology and nanoscale size. Among tested formulations, the most effective showed IC₅₀ values of 0.17 mg/ml for the 3D7 strain and 0.76 mg/ml for the K1 strain, indicating significant antiplasmodial activity. Conclusion: Green-synthesized MgO NPs using A. millefolium demonstrated potent antiplasmodial activity at low IC₅₀ concentrations, showing efficacy against both chloroquine-sensitive and -resistant P. falciparum strains. These findings highlight their promise as plant-based nanotherapeutics for malaria treatment. 249 257 Niloufar Khamsehpour Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Iran Haleh Hanifian Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Iran Mehdi Nateghpour Research Center for Quran, Hadith and Medicine, Tehran University of Medical Sciences Research Center for Quran, Hadith and Medicine, Tehran University of Medical Sciences Iran Ahmad Raeisi Mohammad Shabani Department of Biochemistry, School of Medicine, Iran University of Medical Sciences Department of Biochemistry, School of Medicine, Iran University of Medical Sciences Iran Aram Khezri Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Iran Seyed Ahmad Dehdast Center for Research Endemic Parasites of Iran, Tehran University of Medical Sciences Center for Research Endemic Parasites of Iran, Tehran University of Medical Sciences Iran Leila Farivar Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences Iran Saeed Shahsavari Department of Biostatistics and Epidemiology, School of Health, Alborz University of Medical Sciences Department of Biostatistics and Epidemiology, School of Health, Alborz University of Medical Sciences Iran Gholamreza Hassanpour Achillea millefoliumAntimalarialsChloroquineMagnesium oxidMalariaPlasmodium falciparum 70626.pdf World Health Organization 2024, World Malaria Report 2023, https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2023##Baruah UK, Gowthamarajan K, Vanka R, Karri V, Selvaraj K, Jojo GM. Malaria treatment using novel nano-based drug delivery systems. J Drug Target 2017;25(7):567-81.##Mbatha LS, Akinyelu J, Chukwuma CI, Mokoena MP, Kudanga T. Current Trends and Prospects for Application of Green Synthesized Metal Nanoparticles in Cancer and COVID-19 Therapies. Viruses 2023;15(3):741.##Vitalini S, Beretta G, Iriti M, Orsenigo S, Basilico N, Dall'Acqua S, et al. Phenolic compounds from Achillea millefolium L. and their bioactivity. Acta Biochim Pol 2011;58(2):203-9.##Murnigsih T, Subeki, Matsuura H, Takahashi K, Yamasaki M, Yamato O, et al. Evaluation of the inhibitory activities of the extracts of Indonesian traditional medicinal plants against Plasmodium falciparum and Babesia gibsoni. J Vet Med Sci 2005;67(8):829-31.##N Hasson R. Antibacterial activity of water and alcoholic crude extract of flower Achillea millefolium. Rafidain J Sci 2011;22(5):11-20.##Verma SK, Nisha K, Panda PK, Patel P, Kumari P, Mallick M, et al. Green synthesized MgO nanoparticles infer biocompatibility by reducing in vivo molecular nanotoxicity in embryonic zebrafish through arginine interaction elicited apoptosis. Sci Total Environ 2020;713:136521.##Abdallah Y, Ogunyemi SO, Abdelazez A, Zhang M, Hong X, Ibrahim E, et al. The green synthesis of MgO nano‐flowers using Rosmarinus officinalis L.(Rosemary) and the antibacterial activities against Xanthomonas oryzae pv. oryzae. BioMed Res Int 2019;2019(1):5620989.##Hirphaye BY, Bonka NB, Tura AM, Fanta GM. Biosynthesis of magnesium oxide nanoparticles using Hagenia abyssinica female flower aqueous extract for characterization and antibacterial activity. Applied Water Science 2023;13(9):175.##Berechet MD, Manaila E, Stelescu MD, Craciun G. The composition of essential oils obtained from Achillea millefolium and Matricaria chamomilla L., originary from Romania. Rev Chim 2017;68:2787-95.##Talapko J, Škrlec I, Alebić T, Jukić M, Včev A. Malaria: The Past and the Present. Microorganisms. 2019;7(6):179.##Andrade MV, Noronha K, Diniz BP, Guedes G, Carvalho LR, Silva VA, et al. The economic burden of malaria: a systematic review. Malar J 2022;21(1):283. ##Mohammadi L, Pal K, Bilal M, Rahdar A, Fytianos G, Kyzas GZ. Green nanoparticles to treat patients with Malaria disease: An overview. Journal of Molecular Structure 2021;1229:129857.##Kumar PP, Bhatlu ML, Sukanya K, Karthikeyan S, Jayan N. Synthesis of magnesium oxide nanoparticle by eco friendly method (green synthesis)–A review. Materials Today: Proceedings. 2021 Jan 1;37:3028-30.##Ogunyemi SO, Zhang F, Abdallah Y, Zhang M, Wang Y, Sun G, et al. Biosynthesis and characterization of magnesium oxide and manganese dioxide nanoparticles using Matricaria chamomilla L. extract and its inhibitory effect on Acidovorax oryzae strain RS-2. Artif Cells Nanomed Biotechnol 2019;47(1):2230-9. ##Palanisamy G, Pazhanivel T. Green synthesis of MgO nanoparticles for antibacterial activity. Int Res J Eng Technol. 2017 Aug 4;4(9):137-41.##Rotti RB, Sunitha DV, Manjunath R, Roy A, Mayegowda SB, Gnanaprakash AP, et al. Green synthesis of MgO nanoparticles and its antibacterial properties. Front Chem 2023;11:1143614. ##Fatiqin A, Amrulloh H, Simanjuntak W. Green synthesis of MgO nanoparticles using Moringa oleifera leaf aqueous extract for antibacterial activity. Bulletin of the Chemical Society of Ethiopia 2021;35(1):161-70.##Jeevanandam J, San Chan Y, Danquah MK. Biosynthesis and characterization of MgO nanoparticles from plant extracts via induced molecular nucleation. New Journal of Chemistry 2017;41(7):2800-14.##Kojom Foko LP, Eya’ane Meva F, Eboumbou Moukoko CE, Ntoumba AA, Ngaha Njila MI, Belle Ebanda Kedi P, et al. A systematic review on anti-malarial drug discovery and antiplasmodial potential of green synthesis mediated metal nanoparticles: overview, challenges and future perspectives. Malar J 2019;18(1):337. ##Khan AU, Khan M, Khan AA, Parveen A, Ansari S, Alam M. Effect of Phyto-Assisted Synthesis of Magnesium Oxide Nanoparticles (MgO-NPs) on Bacteria and the Root-Knot Nematode. Bioinorg Chem Appl 2022;3973841. ##Gatou MA, Bovali N, Lagopati N, Pavlatou EA. MgO Nanoparticles as a Promising Photocatalyst towards Rhodamine B and Rhodamine 6G Degradation. Molecules 2024;29(18):4299.##Hanna DH., El-Mazaly MH, Mohamed RR. Synthesis of biodegradable antimicrobial pH-sensitive silver nanocomposites reliant on chitosan and carrageenan derivatives for 5- fluorouracil drug delivery toward HCT116 cancer cells. Int J Biol Macromol 2023;231:123364. ##Parthiban E, Manivannan N, Ramanibai R, Mathivanan N. Green synthesis of silvernanoparticles from Annona reticulata leaves aqueous extract and its mosquito larvicidal and antimicrobial activity on human pathogens. Biotechnol Rep (Amst) 2019;21:e00297. ##Santos AO, Santin AC, Yamaguchi MU, Cortez LE, Ueda-Nakamura T, Dias-Filho BP, et al. Antileishmanial activity of an essential oil from the leaves and flowers of Achillea millefolium. Ann Trop Med Parasitol 2010;104(6):475-83.##Shaba P, Pandey N, Sharma O, Rao J, Mishra A, Singh R. Screening of Achillea millefolium .L (Yarrow) flowers for its antitrypanosomal activity.##Barati A, Huseynzade A, Imamova N, Shikhaliyeva I, Keles S, Alakbarli J, et al. Nanotechnology and malaria: Evaluation of efficacy and toxicity of green nanoparticles and future perspectives. J Vector Borne Dis 2024;61(3):340-56.##Panneerselvam C, Murugan K, Amerasan D. Biosynthesis of silver nanoparticles using plant extract and its anti-plasmodial property. Advanced Materials Research 2015;1086:11-30.##Moraes-de-Souza I, de Moraes BPT, Silva AR, Ferrarini SR, Gonçalves-de-Albuquerque CF. Tiny Green Army: Fighting Malaria with Plants and Nanotechnology. Pharmaceutics 2024;16(6):699. ##

Comparison of CRISPR Sequences in Archaea and Bacteria with Eukaryotic microRNAs 2 2 Background: This study explores repetitive Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) sequences from the archaea Acidianus sp. and Acidianus ambivalens (A. ambivalens), as well as from the bacterium Yersinia ruckeri (Y. ruckeri). These sequences are compared with human microRNA (miRNA) sequences to investigate potential genetic similarities and disease associations. Methods: CRISPR sequences were retrieved from the CRISPR/Cas++ database, and human miRNA sequences were obtained from miRBase. Sequence alignments were performed using BLASTn with an E-value threshold of 1e-5 to identify significant similarities. Genes associated with matched human miRNAs were identified through the HGNC and GeneCards databases. Further analyses included comparison with disease-associated miRNAs reported in human and mouse datasets. Results: In Y. ruckeri, alignments revealed similarities to miRNAs linked with genes such as FOXO1, PTEN, PAX7, and DOCK3, which are associated with lung cancer and muscular dystrophies. In A. ambivalens, aligned miRNAs corresponded to loci including CHM13 and GRCh38, potentially linked to periembolic adenocarcinoma and mild pre-eclampsia. For Acidianus sp., matches were observed with miRNAs associated with genes like Irak2, NOS2, STAT1, and Numb, which have been implicated in Psoriatic arthritis, Alzheimer’s disease, Hepatocellular carcinoma, and Coronary artery disease. Conclusion: CRISPR sequences from these prokaryotes show notable similarities with human miRNAs, suggesting possible indirect links to genes involved in major diseases. These preliminary findings emphasize the need for further investigation into shared sequence motifs and their functional roles in host-pathogen interactions or evolutionary biology. 258 276 Reihaneh Ramezani Faculty of Nanochemical Engineering, Shiraz University Faculty of Nanochemical Engineering, Shiraz University Iran Mandana Behbahani Hassan Mohabatkar Faculty of Biotechnology, Isfahan University Faculty of Biotechnology, Isfahan University Iran Kimia Sarraf Mamouri Faculty of Biotechnology, Isfahan University Faculty of Biotechnology, Isfahan University Iran Fatemeh Hejazi Faculty of Nanochemical Engineering, Shiraz University Faculty of Nanochemical Engineering, Shiraz University Iran AdenocarcinomaArchaeaBacteriaBiologyCRISPR/Cas9Liver neoplasmsMuscular dystrophiesRepetitive CRISPR sequences 70627.pdf Raghuram A, Banskota S, Liu DR. Therapeutic in vivo delivery of gene editing agents. Cell 2022;185(15):2806-27.##Taha EA, Lee J, Hotta A. Delivery of CRISPR-Cas tools for in vivo genome editing therapy: Trends and challenges. J Control Release 2022;342:345-61. ##Li T, Yang Y, Qi H, Cui W, Zhang L, Fu X, et al. CRISPR/Cas9 therapeutics: progress and prospects. Signal Transduct Target Ther 2023;8(1):36. ##Ishibashi R, Maki R, Toyoshima F. Gene targeting in adult organs using in vivo cleavable donor plasmids for CRISPR-Cas9 and CRISPR-Cas12a. Sci Rep 2024;14(1):7615. ##Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 1987;169(12):5429-33. ##Adli M. The CRISPR tool kit for genome editing and beyond. Nat Commun 2018;9(1):1911. ##González F, Zhu Z, Shi ZD, Lelli K, Verma N, Li QV, et al. An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells. Cell Stem Cell 2014;15(2):215-26. ##Zhang XH, Tee LY, Wang XG, Huang QS, Yang SH. Off-target effects in CRISPR/Cas9-mediated genome engineering. Mol Ther Nucleic Acids 2015 Nov 17;4(11):e264. ##Weisheit I, Kroeger JA, Malik R, Klimmt J, Crusius D, Dannert A, et al. Detection of deleterious on-target effects after HDR-mediated CRISPR editing. Cell Rep 2020;31(8):107689. ##Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N, et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 2014;156(5):935-49. ##Höijer I, Emmanouilidou A, Östlund R, Van Schendel R, Bozorgpana S, Tijsterman M, et al. CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations. Nat Commun 2022;13(1):627.##Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 2015;163(3):759-71.##Mojica FJ, Díez-Villaseñor CS, García-Martínez J, Soria E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol 2005;60(2):174-82. ##Bolotin A, Quinquis B, Sorokin A, Ehrlich SD. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology (Reading) 2005;151(Pt 8):2551-61. ##Krysler AR, Cromwell CR, Tu T, Jovel J, Hubbard BP. Guide RNAs containing universal bases enable Cas9/Cas12a recognition of polymorphic sequences. Nat Commun 2022;13(1):1617. ##Hirsch F, Iphofen R, Koporc Z. Ethics assessment in research proposals adopting CRISPR technology. Biochem Med (Zagreb) 2019;29(2):020202.##Cai L, Zheng LA, He L. The forty years of medical genetics in China. J Genet Genomics 2018;45(11):569-82. ##Memi F, Ntokou A, Papangeli I. CRISPR/Cas9 gene-editing: Research technologies, clinical applications, and ethical considerations. Semin Perinatol 2018;42(8):487-500. ##Hundleby PA, Harwood WA. Impacts of the EU GMO regulatory framework for plant genome editing. Food Energy Secur 2019;8(2):e00161. ##Rodriguez E. Ethical issues in genome editing using CRISPR/Cas9 system. Journal of Clinical Research and Bioethics 2016;7(2).##Esvelt KM, Smidler AL, Catteruccia F, Church GM. Concerning RNA-guided gene drives for the alteration of wild populations. Elife 2014;3:e03401.##Shinwari ZK, Tanveer F, Khalil AT. Ethical issues regarding CRISPR-mediated genome editing. Curr Issues Mol Biol 2018;26(1):103-10. ##Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol Direct 2006;1:1-26. ##Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell 2009;136(4):642-55. ##Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007;315(5819):1709-12. ##Garrett RA, Shah SA, Vestergaard G, Deng L, Gudbergsdottir S, Kenchappa CS, et al. CRISPR-based immune systems of the Sulfolobales: complexity and diversity. Biochem Soc Tran 2011;39(1):51-7. ##Garneau JE, Dupuis MÈ, Villion M, Romero DA, Barrangou R, Boyaval P, et al. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 2010;468(7320):67-71.##Sontheimer EJ, Marraffini LA. Slicer for DNA. Nature 2010;468(7320):45-6. ##Mojica FJ, Díez-Villaseñor C, García-Martínez J, Almendros C. Short motif sequences determine the targets of the prokaryotic CRISPR defense system. Microbiology (Reading) 2009;155(3):733-40. ##Deveau H, Barrangou R, Garneau JE, Labonté J, Fremaux C, Boyaval P, et al. Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. J Bacteriol 2008;190(4):1390-400. ##Brouns SJ, Jore MM, Lundgren M, Westra, ER, Slijkhuis RJ, Snijders AP, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 2008;321(5891):960-4. ##Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, et al. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 2011;471(7340):602-7. ##Haurwitz RE, Jinek M, Wiedenheft B, Zhou K, Doudna JA. Sequence-and structure-specific RNA processing by a CRISPR endonuclease. Science 2010;329(5997):1355-8. ##Lyu C, Shen J, Wang R, Gu H, Zhang J, Xue F, et al. Targeted genome engineering in human induced pluripotent stem cells from patients with hemophilia B using the CRISPR-Cas9 system. Stem Cell Research & Therapy 2018;9:1-12.##Yin H, Song CQ, Suresh S, Wu Q, Walsh S, Rhym LH, et al. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Nature biotechnology 2017;35(12):1179-1187.##Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. New England Journal of Medicine 2021;384(3):252-260.##

Nanosilver from Mangosteen Peel Extract (Garcinia mangostana L.) for Antibacterial Dental Preventive Agents 2 2 Background: Teeth are vital structures prone to issues such as caries and plaque formation, often caused by Streptococcus mutans (S. mutans). This issue can be mitigated using natural ingredients like mangosteen fruit (Garcinia mangostana L.), especially its peel, is known for its medicinal benefits. However, its extract may take time to show effects, so it is being combined with nanosilver for improved drug distribution. To observe the antibacterial and antibiofilm potential of Mangosteen Peel Extract (MPE) in nanosilver form as a preventive agent in dentistry. Methods: The extraction was succeeded by a phytochemical assay and biosynthesis of MPE into Mangosteen Peel Extract Nanosilver (MPNs). Particle Size Analysis (PSA) and Transmission Electron Microscopy (TEM) were used to study this procedure. Disc diffusion tests were used to evaluate the antibacterial properties, and the Minimum Inhibition Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were also determined. Furthermore, the antibiofilm activity against S. mutans was investigated. Results: the phytochemical contents in MPE were flavonoids, tannins, saponins, phenols, alkaloids, triterpenoids, and terpenoids. Particle size of MPNs was 126.1 nm and the Polydispersity Index (PDI) was 0.419. The highest antibacterial concentration as inhibition zone against S. mutans was 16.37±0.38 mm and 119.37±2.16% inhibitory activity, at the highest concentration (100%) p<0.05. The percentage of biofilm inhibition against S. mutans was 27.64-105.94% which was concentration dependent. Conclusion: MPNs has potential as an antibacterial and antibiofilm agent that can be used as a preventive agent in medicine. 277 285 Vinna Kurniawati Sugiaman Rosalina Intan Saputri Faculty of Dentistry, Maranatha Christian University, Bandung 40164 Faculty of Dentistry, Maranatha Christian University, Bandung 40164 Indonesia Jeffrey Jeffrey Faculty of Dentistry, Universitas Jenderal Achmad Yani, Cimahi 40531 Faculty of Dentistry, Universitas Jenderal Achmad Yani, Cimahi 40531 Indonesia Wahyu Widowati Faculty of Medicine, Maranatha Christian University, Bandung 40164 Faculty of Medicine, Maranatha Christian University, Bandung 40164 Indonesia Mariska Elisabeth Faculty of Medicine, Maranatha Christian University, Bandung 40164Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 Faculty of Medicine, Maranatha Christian University, Bandung 40164Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 IndonesiaIndonesia Vini Ayuni Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 Indonesia Dhanar Septyawan Hadiprasetyo Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi 40531 Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi 40531 IndonesiaIndonesia Antibacterial agentsGarcinia mangostanaNanoparticle drug delivery systemPhytochemicalsStreptococcus mutans 70628.pdf Tjäderhane L, Paju S. Dentin-Pulp and Periodontal Anatomy and Physiology. In: Essential Endodontology: Prevention and Treatment of Apical Periodontitis. 2019. p. 11-58.##Wiradona I, Setyowati FI, Sadimin S, Utami WJD, Yodong Y. The effectiveness of counselling using animated video on the behaviour regarding dental caries among elementary school students. J Kesehatan Gigi 2022;9(1):47-52.##Pitts NB, Zero DT, Marsh PD, Ekstrand K, Weintraub JA, Ramos-Gomez F. Dental caries. Nat Rev Dis Primers 2017;3(17030):1-6.##Ribeiro AA. Biological features of dental caries. JSM Dent 2016;4(3):1-6.##Setyarini W, Widjiastuti I, Ridwan RD, Kuntaman K. The distribution of Streptococcus mutans and Streptococcus sobrinus in children with dental caries severity level. Majalah Kedokteran Gigi 2020;53(1):36-9.##Lee J, Choi YS, Lee HG. Synergistic antimicrobial properties of nanoencapsulated clove oil. Food Sci Biotechnol 2020;29(11):1597–604.##Sivakumar A, Ravi V, Prasad AS, Sivakumar JS. Herbendodontics–Phytotherapy in endodontics: A review. Biomed Pharmacol J 2018;11(2):1073-82.##Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global prevalence of periodontal disease and lack of its surveillance. Sci World J 2020;2020:2146160.##Nunes R, Broering MF, De Faveri R, Goldoni FC, Mariano LNB, Mafessoli PCM, et al. Effect of the methanolic extract from the leaves of Garcinia humilis Vahl (Clusiaceae) on acute inflammation. Inflammopharmacology 2021;29:423-38.##Andani R, Fajrina A, Asra R, Eriadi A. Antibacterial activity test of mangosteen plants (Garcinia mangostana L.): A review. Asian J Pharm Res Dev 2021;9(1):164-71.##Azam B, Javanzad S, Saleh T, Hashemi M, Aghasadeghi MR. Nanoparticles: Potent vectors for vaccine delivery targeting cancer and infectious diseases. Hum Vaccines Immunother 2014;10(2):321–32.##Hasan KF, Kóczán Z, Horváth PG, Bak M, Horváth A, Bejó L, et al. Green synthesis of nanosilver using Fomes fomentarius mushroom extract over aramid fabrics with improved coloration effects. Text Res J 2022;92(19-20):3567-78.##Saravanakumar K, Chelliah R, Shanmugam S, Varukattu NB, Oh DH, Kathiresan K, et al. Green synthesis and characterization of biologically active nanosilver from seed extract of Gardenia jasminoides Ellis. J Photochem Photobiol B Biol 2018;185:126-35.##Yin IX, Zhang J, Zhao IS, Mei ML, Li Q, Chu CH. The Antibacterial Mechanism of Silver Nanoparticles and Its Application in Dentistry. Int J Nanomedicine 2020;15:2555–62.##Porenczukl A, Grzeczkowicz A, Maciejewska I, Gołaś M, Piskorska K, Kolenda A, et al. An initial evaluation of cytotoxicity, genotoxicity and antibacterial effectiveness of a disinfection liquid containing silver nanoparticles alone and combined with a glass-ionomer cement and dentin bonding systems. Adv Clin Exp Med 2019;28(1):75–83.##De-Deus G, Brandão MC, Fidel RAS, Fidel SR. The sealing ability of GuttaFlow™ in oval-shaped canals: An ex vivo study using a polymicrobial leakage model. Int Endod J 2017;40:794–9.##Patil P, Rathore VP, Hotkar C, Savgave SS, Raghavendra K, Ingale P. A comparison of apical sealing ability between GuttaFlow and AH plus: An in vitro study. Int Soc Prev Community Dent 2016;6:e377-82.##Cataldi A, Gallorini M, Di Giulio M, Guarnieri S, Mariggiò MA, Traine T, et al. Adhesion of human gingival fibroblasts/Streptococcus mitis co-culture on the nanocomposite system Chitlac-nAg. J Mater Sci Mater Med 2016;27:e88.##De Matteis V, Cascione M, Toma CC, Albanese G, De Giorgi ML, Corsalini M, et al. Silver Nanoparticles Addition in Poly (Methyl Methacrylate) Dental Matrix: Topographic and Antimycotic Studies. Int J Mol Sci 2019;20(19):4691.##Cheng L, Zhang K, Zhou CC, Weir MD, Zhou XD, Xu HHK. One-year water-ageing of calcium phosphate composite containing nano-silver and quaternary ammonium to inhibit biofilms. Int J Oral Sci 2016;8:172–81.##Freire PLL, Albuquerque AJR, Sampaio FC, Galembeck A, Flores MA, Stamford T, et al. AgNPs: The New Allies against S. Mutans Biofilm Radhakrishnan—A Pilot Clinical Trial and Microbiological Assay. Braz Dent J 2017;28:417–22.##Ruttkay-Nedecký B, Skalíčková S, Kepinská M, Číhalová K, Dočekalová M, Staňková M, et al. Development of new silver nanoparticles suitable for materials with antimicrobial properties. J Nanoscience Nanotechnology 2019;19(5):2762-9.##Widowati W, Janeva W, Nadya S, Amalia A, Arumwardana S, Kusuma HSW, et al. Antioxidant and antiaging activities of Jasminum sambac extract, and its compounds. J Rep Pharm Sci 2018;7(3):270-85.##Prahastuti S, Hidayat M, Hasiana ST, Widowati W, Widodo WS, Handayani AS, et al. The ethanol extract of the bastard cedar (Guazuma ulmifolia L.) as antioxidants. Pharmaceuticana 2020;10(1):77-88.##Fatima F, Aldawsari MF, Ahmed MM, Anwer MK, Naz M, Ansari MJ, et al. Green synthesized silver nanoparticles using Tridax procumbens for topical application: Excision wound model and histopathological studies. Pharmaceutics 2021;13(11):1754.##Atun S, Arianingrum R, Cahyaningsih L, Pratiwi FA, Kusumaningrum R, Khairuddean M. Formulation and characterization of quercitrin nanoemulsion isolated from Dendropthoe falcata and its antioxidant activity test. Rasayan J Chem 2020;13(3):1347–356.##Widowati W, Wargasetia TL, Kurniawati V, Rachmaniar R, Yuninda VA, Sabrina AHN, et al. In-vitro study of potential antioxidant activities of mangosteen and its nanoemulsions. Med Plants-Int J Phytomed Ind 2023;15(3):534-42.##Koeth LM, DiFranco-Fisher JM, Scangarella-Oman NE, Miller LA. Analysis of MIC and disk diffusion testing variables for gepotidacin and comparator agents against select bacterial pathogens. J Clin Microbiol 2017;55(6):1767-77.##Sugiaman VK, Jeffrey J, Naliani S, Pranata N, Lelyana S, Widowati W, et al. Brazilin cream from Caesalpinia sappan inhibits periodontal disease: in vivo study. PeerJ 2024;12:e17642.##Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal. 2016;6(2):71–9.##Stępień-Pyśniak D, Hauschild T, Kosikowska U, Dec M, Urban-Chmiel R. Biofilm formation capacity and presence of virulence factors among commensal Enterococcus spp. from wild birds. Sci Rep 2019;9(1):11204.##Jeong-Hyon K, Bon-Hyuk G, Sang-Soo N, Yeon-Cheol P. A review of rat models of periodontitis treated with natural extracts. J Tradit Chin Med Sci 2020;7(2):95–103.##Widyarman AS, Lay SH, Wendhita IP, Tjakra EE, Murdono FI, Binartha CTO. Indonesian Mangosteen Fruit (Garcinia mangostana L.) Peel Extract Inhibits Streptococcus mutans and Porphyromonas gingivalis in Biofilms In vitro. Contemp Clin Dent 2019;10(1):123–8.##Widowati W, Ginting CN, Lister INE, Girsang E, Amalia A, Wibowo SHB, et al. Anti-aging Effects of Mangosteen Peel Extract and Its Phytochemical Compounds: Antioxidant Activity, Enzyme Inhibition and Molecular Docking Simulation. Trop Life Sci Res 2020;31(3):127–44.##Widowati W, Darsono L, Suherman J, Yelliantty Y, Maesaroh M. High Performance Liquid Chromatography (HPLC) analysis, antioxidant, antiaggregation of mangosteen peel extract (Garcinia mangostana L.). Int J Biosci Biochem Bioinforma 2014;4(6):458-66.##Gondokesumo ME, Pardiajnto B, Sumitro BS, Widowati W, Handono K. Xanthones analysis and antioxidant activity analysis (applying ESR) of six different maturity levels of mangosteen peel extract (Garcinia mangostana Linn.). Pharmacogn J 2019;11(2):369-73.##Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018;10(2):57.##Granbohm H, Larismaa J, Ali S, Johansson LS, Hannula SP. Control of the size of silver nanoparticles and release of silver in heat treated SiO2-Ag composite powders. Materials 2018;11(1):80.##Sun Y, Yin Y, Mayers B, Herricks T, Xia Y. Uniform silver nanowires synthesis by reducing AgNO3 with ethylene glycol in the presence of seeds and poly(vinyl pyrrolidone). Chem Mater 2022;14(11):4736-45.##Kuzharov A, Milov A, Gerasina J, Soldatov M, Butova V, Soldatov A. Effect of a stabilizer on the structure, synthesis, and tribological properties of silver nanoparticles. Proc Inst Mech Eng Part J J Eng Tribol 2022;237(3):601-10.##Mousavi-Khattat M, Keyhanfar M, Razmjou A. A comparative study of stability, antioxidant, DNA cleavage and antibacterial activities of green and chemically synthesized silver nanoparticles. Artif Cells Nanomed Biotechnol 2018;46(sup3):1022-31.##Sangeetha J, Bhor G, Nitnaware KPG. Biosynthesis of silver nanoparticles using rice grass (Oryza sativa) aqueous leaf extract. J Curr Pharma Res 2019;9(2):2792-8.##Bratovčić A, Dautovic A. Green synthesis of silver nanoparticles using aqueous orange and lemon peel extract and evaluation of their antimicrobial properties. Adv Nanoparticles 2024;13(02):11-28.##Ahmed R, Mustafa D. Green synthesis of silver nanoparticles mediated by traditionally used medicinal plants in Sudan. Int Nano Lett 2019;10(1):1-4.##Rani K. Brief review on recent outcomes of applications of green synthesis vs chemical synthesis of silver nanoparticles. Ip Int J Compr Adv Pharmacol 2020;5(1):9-13.##Tailor G, Yadav B, Chaudhary J, Joshi M, Suvalka C. Green synthesis of silver nanoparticles using Ocimum canum and their anti-bacterial activity. Biochem Biophys Rep 2020;24:100848.##Lakshmanan G, Sathiyaseelan A, Altemimi A, Lakshminarayanan K, Sivaranjan K, Pratap-Singh A, et al. Efficacy of antimicrobial and larvicidal activities of green synthesized silver nanoparticles using leaf extract of Plumbago auriculata Lam. Plants 2020;9(11):1577.##Çelebioğlu H, İmamoğlu R, Taş R. Biogenic synthesis of silver nanoparticles using Trachystemon orientalis L. and their antibacterial activities. 2021.##Taha AA, Patel MP, Hill RG, Fleming PS. The effect of bioactive glasses on enamel remineralization: A systematic review. J Dent 2017;67:9-17.##Pooja Y, Chaitanya P, Vinay C, Uloopi KS, Alla RK, Ahalya P. Antimicrobial and mechanical properties of GIC incorporated with silver vanadate nanoparticles: An in-vitro study. J Clin Diagn Res 2023;17(6):ZC29-ZC32.##Abed FM, Kotha SB, AlShukairi H, Almotawah FN, Alabdulaly RA, Mallineni SK. Effect of different concentrations of silver nanoparticles on the quality of the chemical bond of glass ionomer cement dentine in primary teeth. Front Bioeng Biotechnol 2022;10:816652.##Ogunmodede O, Johnson J, Osunlana R, Olarenwaju S, Ndu-Okeke H. Green biosynthesis of silver nanoparticles using Musa acuminata aqueous flower extract and its antimicrobial activities. CMR 2019.##Moaddabi A, Soltani P, Rengo C, Molaei S, Mousavi SJ, Mehdizadeh M, Spagnuolo G. Comparison of antimicrobial and wound-healing effects of silver nanoparticle and chlorhexidine mouthwashes: an in vivo study in rabbits. Odontology 2022;110(3):577-83.##Craciunescu O, Seciu AM, Zarnescu O. In vitro and in vivo evaluation of a biomimetic scaffold embedding silver nanoparticles for improved treatment of oral lesions. Mater Sci Eng C 2021;123:112015.##Phuong TNM, Hai NTT, Thuy NTT, Phu NV, Huong NT, Nga DTH, et al. Factors affecting synthesis of silver-nanoparticles and antimicrobial applications. Hue Univ J Sci: Nat Sci 2020;129(1D):25-31.##Nguyen PT, Nguyen MT, Quach LT, Nguyen LL, Quyen DV. Antibiofilm activity of alpha-mangostin loaded nanoparticles against Streptococcus mutans. Asian Pac J Trop Biomed 2020;10(7):325-32.##Zhang Y, Pan X, Liao S, Jiang C, Wang L, Tang Y, Wu G, et al. Quantitative proteomics reveals the mechanism of silver nanoparticles against multidrug-resistant Pseudomonas aeruginosa biofilms. Journal of Proteome Research 2020 Jun 22;19(8):3109-22.##Mohamed DS, Abd El-Baky RM, Sandle T, Mandour SA, Ahmed EF. Antimicrobial activity of silver-treated bacteria against other multi-drug resistant pathogens in their environment. Antibiotics 2020;9(4):181.##Kooti M, Sedeh AN, Motamedi H, Rezatofighi SE. Magnetic graphene oxide inlaid with silver nanoparticles as antibacterial and drug delivery composite. Appl Microbiol Biotechnol 2018;102:3607-21.##Dakal TC, Kumar A, Majumdar RS, Yadav V. Mechanistic basis of antimicrobial actions of silver nanoparticles. Front Microbiol 2016;7:1831.##Nalawati AN, Suyatma NE, Wardhana DI. Synthesis of silver nanoparticle (NPAg) using seed aqueous extract of Jatropha curcas L and their anti-bacterial activity assessment. J Teknol dan Industri Pangan 2022;32(2):98-106.##Xu GY, Zhao IS, Lung CY, Yin IX, Lo EC, Chu CH. Silver Compounds for Caries Management. Int Dent J 2023;74(2):179-86.##Shibata MA, Matoba Y, Tosa H, Iinuma M. Effects of mangosteen pericarp extracts against mammary cancer. Altern Integr Med 2013;2(8):1–5.##Miladiyah I, Rachmawaty FJ. Potency of xanthone derivatives as antibacterial agents against Methicillin-Resistant Staphylococcus aureus (MRSA). JKKI: Jurnal Kedokteran dan Kesehatan Indonesia 2017;124-135.##Recordati C, Maglie M, Bianchessi S, Argentiere S, Cella C, Mattiello S, et al. Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects. Part Fibre Toxicol 2015;13(1):12.##

Comparative Expression of ADAMTS2, CA1, and OLAH in Immune Cells of Rheumatoid Arthritis Patients: Real-time PCR Study on In-silico analysis of Treated vs. Newly Diagnosed Patients 2 2 Background: Rheumatoid Arthritis (RA) is a chronic inflammatory joint disease. Current treatments often have limited efficacy and cause side effects due to their nonspecific action, while early diagnosis is challenging. This study combined bioinformatics and experimental methods to identify key genes and pathways involved in RA, aiming to discover novel therapeutic targets and diagnostic biomarkers. Methods: RNA-seq data from immune cells of RA patients and healthy donors (GSE117769) were analyzed with DESeq to identify Differentially Expressed Genes (DEGs). Affected pathways were explored using EnrichR, and druggable genes were identified through DGIdb and a literature review. Expression of candidate genes was validated in additional RA blood and synovium microarray datasets (GSE45291, GSE82107, GSE77298) using the GEO2R tool. Finally, RT-qPCR was used to measure the expression of selected genes in Peripheral blood Mononuclear Cells (PBMCs) from newly-diagnosed and chronic RA patients and controls, with associations to clinical features and diagnostic accuracy assessed. Synovial fluid of RA patients were stained with Giemsa. Results: Combined in-silico and experimental analysis demonstrated significant upregulation of CA1, OLAH, and ADAMTS2 in the PBMCs of RA patients. However, only ADAMTS2 showed high expression in the synovial tissue of these patients. While OLAH and ADAMTS2 were predominantly overexpressed in newly-diagnosed cases, CA1 levels were consistently elevated in both early and chronic stages of RA. Conclusion: This study identified CA1, OLAH, and ADAMTS2 as being upregulated in RA, with ADAMTS2 showing promise as a therapeutic target, suggesting it may also have potential as a candidate for diagnosis and treatment. 286 292 Fatemeh Dehghan Laboratory Sciences Research Center, Golestan University of Medical Sciences Laboratory Sciences Research Center, Golestan University of Medical Sciences Iran Zahra Bazi Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical SciencesCancer Research Center, Golestan University of Medical Sciences Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical SciencesCancer Research Center, Golestan University of Medical Sciences IranIran Mehrdad Aghaei Golestan Rheumatology Research Center, Golestan University of Medical Science Golestan Rheumatology Research Center, Golestan University of Medical Science Iran Masoomeh Gholizadeh Metabolic Disorders Research Center, Biomedical Research Institute, Golestan University of Medical Sciences Metabolic Disorders Research Center, Biomedical Research Institute, Golestan University of Medical Sciences Iran Romina Malakouti Laboratory Sciences Research Center, Golestan University of Medical Sciences Laboratory Sciences Research Center, Golestan University of Medical Sciences Iran Zahra Hesari Computational biologyMononuclear leukocytesRheumatoid arthritisRNA-SeqSynovial membraneUp-regulation 70629.pdf Zhang Z, Gao X, Liu S, Wang Q, Wang Y, Hou S, et al. Global, regional, and national epidemiology of rheumatoid arthritis among people aged 20–54 years from 1990 to 2021. Sci Rep 2025;15(1):10736.##Arima H, Koirala S, Nema K, Nakano M, Ito H, Poudel KM, et al. High prevalence of rheumatoid arthritis and its risk factors among Tibetan highlanders living in Tsarang, Mustang district of Nepal. J Physiol Anthropol 2022;41(1):12.##Almutairi K, Nossent J, Preen D, Keen H, Inderjeeth C. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatol Int 2021;41(5):863-77.##Conigliaro P, Triggianese P, De Martino E, Fonti GL, Chimenti MS, Sunzini F, et al. Challenges in the treatment of rheumatoid arthritis. Autoimmun Rev 2019;18(7):706-13.##Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res 2018;6(1):15. ##McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet 2017;389(10086):2328-37. ##He Q, Ding H. Bioinformatics analysis of rheumatoid arthritis tissues identifies genes and potential drugs that are expressed specifically. Sci Rep 2023;13(1):4508. ##Tashian RE. Genetics of the mammalian carbonic anhydrases. Adv Genet 1992;30:321-56. ##Ji MJ, Hong JH. An overview of carbonic anhydrases and membrane channels of synoviocytes in inflamed joints. J Enzyme Inhib Med Chem 2019;34(1):1615-22.##Zheng Y, Wang L, Zhang W, Xu H, Chang X. Transgenic mice over-expressing carbonic anhydrase I showed aggravated joint inflammation and tissue destruction. BMC Musculoskelet Disord 2012 Dec 20;13:256.##Alper M, Aydemir AT, Köçkar F. Induction of human ADAMTS-2 gene expression by IL-1α is mediated by a multiple crosstalk of MEK/JNK and PI3K pathways in osteoblast like cells. Gene 2015;573(2):321-7.##Li M, Van Esch BC, Wagenaar GT, Garssen J, Folkerts G, Henricks PA. Pro-and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells. Eur J Pharmacol 2018;831:52-9.##Cotto KC, Wagner AH, Feng YY, Kiwala S, Coffman AC, Spies G, et al. DGIdb 3.0: a redesign and expansion of the drug–gene interaction database. Nucleic Acids Res 2018;46(D1):D1068-D73. ##Bienkowska J, Allaire N, Thai A, Goyal J, Plavina T, Nirula A, et al. Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. PLoS One 2014;9(11):e112545.##Broeren MG, De Vries M, Bennink MB, Van Lent PL, Van Der Kraan PM, Koenders MI, et al. Functional tissue analysis reveals successful cryopreservation of human osteoarthritic synovium. PLoS One 2016;11(11):e0167076.##Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun 2020;110:102400.##Hofer TP, Frankenberger M, Mages J, Lang R, Hoffmann R, Colige A, et al. Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids. J Mol Med (Berl) 2008;86:323-32.##Leduc C, Dupont L, Joannes L, Monseur C, Baiwir D, Mazzucchelli G, et al. In vivo N-terminomics highlights novel functions of ADAMTS2 and ADAMTS14 in skin collagen matrix building. Front Mol Biosci 2021;8:643178. ##Lin EA, Liu CJ. The role of ADAMTSs in arthritis. Protein Cell 2010;1(1):33-47.##Villeval JL, Testa U, Vinci G, Tonthat H, Bettaieb A, Titeux M, et al. Carbonic anhydrase I is an early specific marker of normal human erythroid differentiation. Blood 1985 Nov;66(5):1162-70.##Mboge MY, Mahon BP, McKenna R, Frost SC. Carbonic anhydrases: role in pH control and cancer. Metabolites 2018;8(1):19.##Ivanov S, Liao SY, Ivanova A, Danilkovitch-Miagkova A, Tarasova N, Weirich G, et al. Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am J Pathol 2001;158(3):905-19.##Strowitzki MJ, Nelson R, Garcia MP, Tuffs C, Bleul MB, Fitzsimons S, et al. Carbon Dioxide Sensing by Immune Cells Occurs through Carbonic Anhydrase 2–Dependent Changes in Intracellular pH. J Immunol 2022;208(10):2363-75.##Hudalla H, Michael Z, Christodoulou N, Willis GR, Fernandez-Gonzalez A, Filatava EJ, et al. Carbonic anhydrase inhibition ameliorates inflammation and experimental pulmonary hypertension. Am J Respir Cell Mol Biol 2019;61(4):512-24.##Hidalgo MA, Carretta MD, Burgos RA. Long chain fatty acids as modulators of immune cells function: contribution of FFA1 and FFA4 receptors. Front Physiol 2021;12:668330.##Lei Q, Yang J, Li L, Zhao N, Lu C, Lu A, et al. Lipid metabolism and rheumatoid arthritis. Front Immunol 2023;14:1190607.##

Plant-Based Recombinant Vaccines for Foot-and-Mouth Disease: A Meta-Synthesis 2 2 Background: Foot-and-Mouth Disease (FMD) remains a persistent global threat to livestock health and food security, particularly in endemic and resource-constrained regions. Conventional inactivated vaccines pose several challenges—including biosafety risks and dependence on cold-chain logistics. These limitations have prompted growing interest in plant-based recombinant vaccine platforms as innovative, scalable, and safer alternatives for FMD prevention. Methods: This study employed a qualitative meta-synthesis approach, guided by the Barroso–Sandelowski method, to systematically extract, interpret, and integrate findings from 35 peer-reviewed empirical studies published between 2000 and 2025. The selected studies focused on the development and evaluation of plant-made vaccines targeting FMD. Thematic coding and interpretive synthesis were applied to identify recurrent patterns, challenges, and opportunities across the literature. Results: The analysis yielded four dominant themes: (1) Platform Diversity: A variety of plant and algal expression hosts were used through transient or stable transformation systems, (2) Immunization Routes: Oral vaccination was noted for its logistical advantages and potential for mass immunization, though often requiring adjuvants to enhance immunogenicity, (3) Scale-Up Challenges: Key barriers included low recombinant protein yields, heterogeneity in post-translational modifications and high variability between production batches and (4) Regulatory Readiness: Despite encouraging preclinical data, most candidates have not progressed beyond experimental stages. Conclusion: Plant-based recombinant vaccines represent a promising frontier in the fight against FMD, offering novel avenues for safer, more accessible immunization strategies. However, their transition from bench to field remains hindered by technical limitations in expression and purification, as well as institutional and regulatory gaps. 293 302 Maziar Habibi-Pirkoohi Afsaneh Mohkami Research and Technology Institute of Plant Production, Afzalipour Research Institute, Shahid Bahonar University of Kerman Research and Technology Institute of Plant Production, Afzalipour Research Institute, Shahid Bahonar University of Kerman Iran Containment of biohazardsFoot and mouth diseaseLivestockMass vaccinationVaccines 70630.pdf Lee HJ, Ko YJ. The C3d-fused foot-and-mouth disease vaccine platform overcomes maternally derived antibody interference. NPJ Vaccines 2022;7(1):70.##Liu W, Yang B, Wang M, Liang W, Wang H, Yang D. Identification of a conserved conformational epitope in the VP2 protein of FMDV. Arch Virol 2017;162(7):1877-85.##Elrashedy A, Nayel M, Salama A, Zaghawa A, El-Shabasy RM, Hasan ME. Foot-and-mouth disease: genomic and proteomic structure, antigenic sites, serotype relationships, immune evasion, recent vaccine development strategies, and future perspectives. Vet Res 2025;56(1):78.##Kenubih A. Foot and mouth disease vaccine development and challenges in inducing long-lasting immunity: trends and current perspectives. Vet Med (Auckl) 2021;12:205-15.##Lu Z, Yu S, Wang W, Chen W, Wang X, Wu K, et al. Development of foot-and-mouth disease vaccines in recent years. Vaccines 2022;10(11):1817.##Alsharifi M, Rybicki EP, Meyers AE. Plant-produced virus-like particles: A promising platform for future FMD vaccines. Plants 2022;13(24):3564.##Habibi Pirkoohi M, Mohkami A. Recombinant vaccine production in green plants: state of the art. J Cell Mol Res 2015;7(1):59-67.##Habibi Pirkoohi M, Malekzadeh Shafaroudi S, Marashi H, Moshtaghi N, Zibaee S. Transient expression of FMDV coat protein in tobacco (Nicotiana tabacum) via agroinfiltration. Iran J Biotechnol 2014;12(1):28-34.##Mignaqui AC, Ferella A, Sánchez C, Stuible M, Scian R, Filippi J, et al. Optimized production of virus-like particles in a high-CHO-cell-density transient gene expression system for foot-and-mouth disease vaccine development. Vaccines (Basel) 2025;13(6):581.##Habibi Pirkoohi M, Malekzadeh Shafaroudi S, Marashi H, Moshtaghi N, Nasiri M, Zibaee S. Transient expression of FMDV coat protein in spinach (Spinacia oleracea) via agroinfiltration. J Plant Mol Breed 2015;2(2):18-27.##Veerapen VP, Van Zyl AR, Wigdorovitz A, Rybicki EP, Meyers AE. Novel expression of immunogenic foot-and-mouth disease virus-like particles in Nicotiana benthamiana. Virus Res. 2018;244:213-7.##Parizipour MHG, Shahriari AG, Habibi-Pirkoohi M. Transient gene expression: An approach for recombinant vaccine production. J Med Microbiol Infect Dis 2021;9(1):46-54.##Sun M, Qian K, Su N, Chang H, Liu J, Shen G. FMDV VP1 fused with cholera toxin B subunit expressed in Chlamydomonas reinhardtii chloroplast. Biotechnol Lett 2003;25(13):1087-92.##Walmsley AM, Arntzen CJ. Plants for delivery of edible vaccines. Curr Opin Biotechnol 2000;11(2):126-9.##Rybicki EP. Plant-based vaccines against viruses. Virol J 2014;11:205.##Cui B, Liu X, Zhou P, Fang Y, Zhao D, Zhang Y, et al. Immunogenicity and protective efficacy of recombinant proteins consisting of multiple epitopes of foot-and-mouth disease virus fused with flagellin. Appl Microbiol Biotechnol 2019;103(8):3367-79.##Akter S, Rahman MS, Islam MR, Akther M, Anjume H, Marjia M, et al. Development of recombinant proteins for vaccine candidates against serotypes O and A of foot-and-mouth disease virus in Bangladesh. Access Microbiol 2024;6(6):000713-v4.##Wu P, Yin X, Liu Q, Wu W, Chen C. Recombinant T7 phage with FMDV AKT-III strain VP1 protein is a potential FMDV vaccine. Biotechnol Lett 2021;43(1):35-41.##Mignaqui AC, Ferella A, Cass B, Mukankurayija L, L’Abbé D, Bisson L, et al. Foot-and-mouth disease: Optimization, reproducibility, and scalability of high-yield production of virus-like particles for a next-generation vaccine. Front Vet Sci 2020;7:601.##Song BM, Lee GH, Kang SM, Tark D. Evaluation of vaccine efficacy with 2B/T epitope conjugated porcine IgG-Fc recombinants against foot-and-mouth disease virus. J Vet Med Sci 2024;86(9):999-1007.##Cao Y, Li D, Fu Y, Bai Q, Chen Y, Bai X, et al. Rational design and efficacy of a multi-epitope recombinant protein vaccine against foot-and-mouth disease virus serotype A in pigs. Antiviral Res 2017;140:133-41.##Shoji Y, Farrance CE. Plant-produced vaccines for animal health and productivity. Plant Cell Rep 2014;33(5):733-9.##Carter JE III, Langridge WHR. Plant-based vaccines for protection against infectious and autoimmune diseases. Crit Rev Plant Sci 2002;21(1):93-109.##Fang M, Li J, Wang H, Yang M, Zhang Y, Zhou L, et al. Correlation between efficacy and structure of recombinant epitope vaccines against bovine type O FMDV. Biotechnol Lett 2012;34(5):839-47.##Chinsangaram J, Smith D, Johnson M. Expression and immunogenicity of foot-and-mouth disease virus VP1 antigen in transgenic maize. Plant Biotechnol J 2023;21(4):567-79.##Sala F, Rigano MM, Barbante A, Basso B, Walmsley AM, Castiglione S. Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives. Vaccine 2003;21(7-8):803-8.##Lee HB, Piao DC, Lee JY, Choi JY, Bok JD, Cho CS, et al. Artificially designed recombinant protein composed of multiple epitopes of foot-and-mouth disease virus as a vaccine candidate. Microb Cell Fact 2017;16:1-10.##He DM, Qian KX, Shen GF, Li YN, Zhang ZF, Su ZL, et al. Stable expression of foot-and-mouth disease virus protein VP1 fused with cholera toxin B subunit in potato (Solanum tuberosum). Biointerfaces 2007;55:159-63.##Huang YH, Liang WQ, Wang YJ, Zhou ZI, Pan A, Yang XH, et al. Immunogenicity of the epitope of the foot-and-mouth disease virus fused with a hepatitis B core protein in transgenic tobacco. Viral Immunol 2005;18(4):668-77.##Dus Santos MJ, Carrillo C, Ardila F, Ríos RD, Franzone P, Piccone ME, et al. Development of transgenic alfalfa plants containing the FMDV structural polyprotein gene P1 and its utilization as an experimental immunogen. Vaccine. 2005;23(13):1838-43.##Yu SC, Lee IK, Kong HS, Shin SH, Hwang SY, Ahn YJ, et al. Foot-and-mouth disease virus-like particles produced in E. coli as potential antigens for a novel vaccine. Vet Sci 2025;12(6):539.##Zhang YL, Guo YJ, Wang KY, Lu K, Li K, Zhu Y, et al. Enhanced immunogenicity of modified hepatitis B virus core particle fused with multiepitopes of foot-and-mouth disease virus. Scand J Immunol 2007;65(4):320-8.##Shahriari A, Habibi Pirkoohi M. Developing vaccines against foot-and-mouth disease: a biotechnological approach. Arch Razi Inst 2018;73(1):1-10.##

Dual-Modality Therapy: Synergistic Enhancement of Radio-Hyperthermia by Gold-Gold Sulfide Nanoparticles in MCF-7 Cells 2 2 Background: This study examines the synergistic impact of Gold-Gold Sulfide (GGS) nanoparticles combined with hyperthermia and radiotherapy on MCF-7 cancer cells. GGS nanoparticles, with strong near-infrared absorption and photothermal properties, enhance cellular sensitivity to radiotherapy. Methods: MCF-7 cells were treated with varying GGS concentrations and exposed to radiation doses of 50, 100, and 200 cGy, alongside laser irradiation for 10, 40, and 80 s. The IC50 for GGS nanoparticles was approximately 350 µM. Results: Results revealed a significant reduction in cell viability with the combined GGS and laser exposure (p<0.001), demonstrating a synergistic effect in a dose-dependent manner. Further enhancement in cell viability reduction was observed when GGS nanoparticles were combined with both hyperthermia and radiotherapy (p<0.01). Conclusion: These findings suggest that GGS nanoparticles offer greater efficacy and reduced toxicity compared to gold nanoparticles, highlighting their potential for improving cancer therapy outcomes through combined hyperthermic and radiotherapeutic approaches. 303 311 Mahdi Sadat-Darbandi Department of Medical Physics, Reza Radiotherapy and Oncology Center Department of Medical Physics, Reza Radiotherapy and Oncology Center Iran Amirhossein Fathabadi Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical SciencesStudent Research Committee, Mashhad University of Medical Sciences Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical SciencesStudent Research Committee, Mashhad University of Medical Sciences IranIran Shabnam Oloomi Ameneh Sazgarnia Cell survivalHyperthermiaInducedMetal nanoparticlesMCF-7 cellsRadiotherapy 70631.pdf Mohamed WA, El-Nekhily NA, Mahmoud HE, Hussein AA, Sabra SA. Prodigiosin/celecoxib-loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer. Scientific Reports. 2024;14:181.##System NH. Breast cancer in women, https://www.nhs.uk/conditions/breast-cancer/##Khan MR, Alafaleq NO, Ramu AK, Alhosaini K, Khan MS, Zughaibi TA, et al. Evaluation of biogenically synthesized MgO NPs anticancer activity against breast cancer cells. Saudi Journal of Biological Sciences. 2024;31:103874.##Marques A, Belchior A, Silva F, Marques F, Campello MPC, Pinheiro T, et al. Dose Rate Effects on the Selective Radiosensitization of Prostate Cells by GRPR-Targeted Gold Nanoparticles. Int J Mol Sci. 2022;23:5279.##Abdollahi BB, Ghorbani M, Hamishehkar H, Malekzadeh R, Farajollahi A. Synthesis and characterization of actively HER-2 Targeted Fe3O4@ Au nanoparticles for molecular radiosensitization of breast cancer. BioImpacts: BI. 2023;13:17.##Neshastehriz A, Khosravi Z, Ghaznavi H, Shakeri-Zadeh A. Gold-coated iron oxide nanoparticles trigger apoptosis in the process of thermo-radiotherapy of U87-MG human glioma cells. Radiat Environ Biophys. 2018;57:405-418.##Kim JY, Lee WS, Seo SJ, Jung CW, Kim EH. Effects of gold nanoparticles on normal hepatocytes in radiation therapy. Transl Cancer Res. 2022;11:2572-2581.##Logghe T, Van Zwol E, Immordino B, Van den Cruys K, Peeters M, Giovannetti E, et al. Hyperthermia in combination with emerging targeted and immunotherapies as a new approach in cancer treatment. Cancers. 2024;16:505.##Shahamat Z, Shokouhi M, Taheri AR, Eshghi H, Attaran-Kakhki N, Sazgarnia A. Induction of Localized Hyperthermia by Millisecond Laser Pulses in the Presence of Gold-Gold Sulphide Nanoparticles in a Phantom. Iranian Journal of Medical Physics. 2015;12:49-61.##Hadi F, Tavakkol S, Laurent S, Pirhajati V, Mahdavi SR, Neshastehriz A, et al. Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto-plasmonic nanoparticles on MCF-7 breast cancer cells. J Cell Physiol. 2019;234:20028-20035.##Zhang A, Gao L. The Refined Application and Evolution of Nanotechnology in Enhancing Radiosensitivity During Radiotherapy: Transitioning from Gold Nanoparticles to Multifunctional Nanomaterials. Int J Nanomedicine. 2023;18:6233-6256.##Bala VM, Lampropoulou DI, Grammatikaki S, Kouloulias V, Lagopati N, Aravantinos G, et al. Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer. Int J Mol Sci. 2023;25:296.##Stephen ZR, Zhang M. Recent Progress in the Synergistic Combination of Nanoparticle-Mediated Hyperthermia and Immunotherapy for Treatment of Cancer. Adv Healthc Mater. 2021;10:e2001415.##Kazemzadeh A, Moradi H. A Monte Carlo Study on Dose Enhancement in the Presence of Nanoparticles by Photon Source: A Comparison between Various Concentration and Material of Nanoparticles. Frontiers in Biomedical Technologies. 2021;8:191-197.##Faid AH, Shouman SA, Badr YA, Sharaky M. Enhanced photothermal heating and combination therapy of gold nanoparticles on a breast cell model. BMC Chem. 2022;16:66.##Malekzadeh R, Mortezazadeh T, Abdulsahib WK, Babaye Abdollahi B, Hamblin MR, Mansoori B, et al. Nanoarchitecture-based photothermal ablation of cancer: A systematic review. Environ Res. 2023;236:116526.##Mortezaee K, Narmani A, Salehi M, Bagheri H, Farhood B, Haghi-Aminjan H, et al. Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer. Life Sci. 2021;269:119020.##D'Acunto M, Cioni P, Gabellieri E, Presciuttini G. Exploiting gold nanoparticles for diagnosis and cancer treatments. Nanotechnology. 2021;32:192001.##Ghorbani F, Attaran-Kakhki N, Sazgarnia A. The synergistic effect of photodynamic therapy and photothermal therapy in the presence of gold-gold sulfide nanoshells conjugated Indocyanine green on HeLa cells. Photodiagnosis Photodyn Ther. 2017;17:48-55.##Kepp O, Cerrato G, Sauvat A, Kroemer G. Nanoparticles releasing immunogenic cell death inducers upon near-infrared light exposure. 2022;11:2131227.##Liaw JW, Kuo CY, Tsai SW. The Effect of Quasi-Spherical Gold Nanoparticles on Two-Photon Induced Reactive Oxygen Species for Cell Damage. Nanomaterials (Basel). 2021;11:1180.##Chen Y, Zhang Y, Liang W, Li X. Gold nanocages as contrast agents for two-photon luminescence endomicroscopy imaging. Nanomedicine: Nanotechnology, Biology and Medicine. 2012;8:1267-1270.##Zhang Y, Liu AT, Cornejo YR, Van Haute D, Berlin JM. A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings. PLoS One. 2020;15:e0234916.##Minaei SE, Khoei S, Khoee S, Mahdavi SR. Sensitization of glioblastoma cancer cells to radiotherapy and magnetic hyperthermia by targeted temozolomide-loaded magnetite tri-block copolymer nanoparticles as a nanotheranostic agent. Life Sciences. 2022;306:120729.##Wang Y, Zou L, Qiang Z, Jiang J, Zhu Z, Ren J. Enhancing Targeted Cancer Treatment by Combining Hyperthermia and Radiotherapy Using Mn-Zn Ferrite Magnetic Nanoparticles. ACS Biomater Sci Eng. 2020;6:3550-3562.##Esmaeili Govarchin Ghaleh H, Zarei L, Mansori Motlagh B, Jabbari N. Using CuO nanoparticles and hyperthermia in radiotherapy of MCF-7 cell line: synergistic effect in cancer therapy. Artif Cells Nanomed Biotechnol. 2019;47:1396-1403.##Jabbari N, Zarei L, Esmaeili Govarchin Galeh H, Mansori Motlagh B. Assessment of synergistic effect of combining hyperthermia with irradiation and calcium carbonate nanoparticles on proliferation of human breast adenocarcinoma cell line (MCF-7 cells). Artif Cells Nanomed Biotechnol. 2018;46:364-372.##Day ES, Bickford LR, Slater JH, Riggall NS, Drezek RA, West JL. Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer. International journal of nanomedicine. 2010:445-454.##Ramezanzadeh E, Sadri K, Momennezhad M, Dolat E, Sazgarnia A. Evaluation of EGFR-targeted gold/gold sulfide (GGS) nanoparticles as a theranostic agent in photothermal therapy. Materials Research Express. 2018;5:125401.##Sadat Shandiz SA, Shafiee Ardestani M, Shahbazzadeh D, Assadi A, Ahangari Cohan R, Asgary V, et al. Novel imatinib-loaded silver nanoparticles for enhanced apoptosis of human breast cancer MCF-7 cells. Artif Cells Nanomed Biotechnol. 2017;45:1-10.##Sadeghi HR, Bahreyni-Toosi MH, Meybodi NT, Esmaily H, Soudmand S, Eshghi H, et al. Gold-gold sulfide nanoshell as a novel intensifier for anti-tumor effects of radiofrequency fields. Iranian Journal of Basic Medical Sciences. 2014;17:516.##Li H, Beetsma L, Prakash S, Mikkers M, Botto L. Analysis and optimization of a multicascade method for the size fractionation of poly-dispersed particle systems via sedimentation or centrifugation. arXiv preprint arXiv:2303.05257. 2023.##Ma J, Li N, Wang J, Liu Z, Han Y, Zeng Y. In vivo synergistic tumor therapies based on copper sulfide photothermal therapeutic nanoplatforms Exploration, Wiley Online Library, pp 20220161.##Maestro LM, Haro-González P, Coello JG, Jaque D. Absorption efficiency of gold nanorods determined by quantum dot fluorescence thermometry. Applied Physics Letters. 2012;100.##Maestro LM, Haro-González P, Coello JG, Jaque D. Absorption efficiency of gold nanorods determined by quantum dot fluorescence thermometry. Applied Physics Letters. 2012;100.##Upadhyay C, Tripathy K, Bhattacharjee M. Scattering and Absorption Efficiency Analysis of Gold Nanospheres for Optoelectronic Applications 2024 8th IEEE Electron Devices Technology & Manufacturing Conference (EDTM), IEEE, pp 1-3.##Gobin AM, Watkins EM, Quevedo E, Colvin VL, West JL. Near‐infrared‐resonant gold/gold sulfide nanoparticles as a photothermal cancer therapeutic agent. Small. 2010;6:745-752.##Saifi MA, Khan W, Godugu C. Cytotoxicity of Nanomaterials: Using Nanotoxicology to Address the Safety Concerns of Nanoparticles. Pharm Nanotechnol. 2018;6:3-16.##Dhiman S, Bakshi P, Kapoor N, Sharma P, Kohli S K, Mir B A, et al. Nanoparticle-Induced Oxidative Stress in Plant. Plant Responses to Nanomaterials: Recent Interventions, and Physiological and Biochemical Responses. 2021:269-313.##Vijayalakshmi S, Rajasekar A, Veeraraghavan VP, Ghidan AY, Al Antary TM, Karthikkumar V, et al. The pro-apoptotic and cytotoxic efficacy of polydatin encapsulated poly (lactic-co-glycolic acid)(PLGA) nanoparticles. Process Biochemistry. 2021;111:210-218.##Chang X, Wang X, Li J, Shang M, Niu S, Zhang W, et al. Silver nanoparticles induced cytotoxicity in HT22 cells through autophagy and apoptosis via PI3K/AKT/mTOR signaling pathway. Ecotoxicology and Environmental Safety. 2021;208:111696.##Al‐Asiri WY, Al‐Sheddi ES, Farshori NN, Al‐Oqail MM, Al‐Massarani SM, Malik T, et al. Cytotoxic and Apoptotic Effects of Green Synthesized Silver Nanoparticles via Reactive Oxygen Species–Mediated Mitochondrial Pathway in Human Breast Cancer Cells. Cell Biochemistry and Function. 2024;42:e4113.##Ramachandran R, Krishnaraj C, Kumar VA, Harper SL, Kalaichelvan TP, Yun SI. In vivo toxicity evaluation of biologically synthesized silver nanoparticles and gold nanoparticles on adult zebrafish: a comparative study. 3 Biotech. 2018;8:1-12.##Ghahremani FH, Sazgarnia A, Bahreyni-Toosi MH, Rajabi O, Aledavood A. Efficacy of microwave hyperthermia and chemotherapy in the presence of gold nanoparticles: an in vitro study on osteosarcoma. Int J Hyperthermia. 2011;27:625-36.##Mohammadi A, Hashemi B, Mehdi Mahdavi SR, Solimani M, Banaei A. Radiosensitization effect of radiofrequency hyperthermia in the presence of PEGylated-gold nanoparticles on the MCF-7 breast cancer cells under 6 MeV electron irradiation. J Cancer Res Ther. 2023;19:S67-S73.##Pu Y, Pons T. Gold Nanorod/Titanium Dioxide Hybrid Nanoparticles for Plasmon-Enhanced Near-Infrared Photoproduction of Hydroxyl Radicals and Photodynamic Therapy. ACS Applied Materials & Interfaces. 2023;15:49943-49952.##Etemadi M, Golmohammadi S, Akbarzadeh A, Rasta SH. Plasmonic photothermal therapy in the near-IR region using gold nanostars. Applied Optics. 2023;62:764-773.##Lo CY, Tsai SW, Niu H, Chen FH, Hwang HC, Chao TC, et al. Gold-nanoparticles-enhanced production of reactive oxygen species in cells at spread-out Bragg peak under proton beam radiation. ACS omega. 2023;8:17922-17931.##Ma N, Wu FG, Zhang X, Jiang YW, Jia HR, Wang HY, et al. Shape-dependent radiosensitization effect of gold nanostructures in cancer radiotherapy: comparison of gold nanoparticles, nanospikes, and nanorods. ACS applied materials & interfaces. 2017;9:13037-13048.##Taheri A, Khandaker MU, Moradi F, Bradley DA. A simulation study on the radiosensitization properties of gold nanorods. Physics in Medicine & Biology. 2024;69:045029.##