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Beyond DNA Mutations in Liquid Biopsy: From a Primarily Genotypic Tool to a Functional Plasma Biomarker 2 2 Liquid biopsy is considered an innovative revolutionary technology in precision medicine and offers non-invasive and real-time molecular profiling of individual patients. Over the past decade, the analysis of circulating tumor DNA (ctDNA) has become nearly synonymous with the term of "liquid biopsy". The discovery of somatic mutations, copy number variations, and epigenetic signatures in cell-free(cf)DNA from peripheral blood has revolutionized oncological diagnostics enabling genotyping from a simple venipuncture, tracking of clonal evolution, and detection of minimal residual disease with remarkable sensitivity. Yet a conceptual limitation has quietly accompanied these remarkable progresses. Most current liquid biopsy methods answer one essential question: What genetic alterations are present? However, they do not directly answer a question equally central to clinical pathophysiology: What is the disease actively doing in real time? 1 10 2026/06/10 1405/3/20 2026/06/16 1405/3/26 Ali Noori-Zadeh Ali Noori-Zadeh Department of Clinical Biochemistry, Faculty of Medicine, Ilam University Medical Sciences, Ilam, Iran Iran noorizadeh-a@medilam.ac.ir Liquid biopsy pathophysiology exosomes circulating tumor DNA cell-free mitochondria laboratory medicine functional biomarkers Lin B, Lei Y, Wang J, Zhu L, Wu Y, Zhang H, et al. Microfluidic-Based Exosome Analysis for Liquid Biopsy. Small Methods. 2021;5(3):2001131. doi:##Ma L, Guo H, Zhao Y, Liu Z, Wang C, Bu J, et al. Liquid biopsy in cancer: current status, challenges and future prospects. Signal Transduction and Targeted Therapy. 2024;9(1):336. doi:##Abreu RDS, Ferreira DDP, de Araujo NS, Horita S, Tilli TM, Degrave W, et al. Liquid biopsy in cancer diagnosis and prognosis: a paradigm shift in precision oncology. Frontiers in molecular biosciences. 2025;12:1708518. doi:##Wan R, Wang Z, Lee JJ, Wang S, Li Q, Tang F, et al. Comprehensive analysis of the discordance of EGFR mutation status between tumor tissues and matched circulating tumor dna in advanced non–small cell lung cancer. Journal of Thoracic Oncology. 2017;12(9):1376-87. doi:##Garrido-Navas MC, García-Díaz A, Molina-Vallejo MP, González-Martínez C, Alcaide Lucena M, Cañas-García I, et al. The polemic diagnostic role of TP53 mutations in liquid biopsies from breast, colon and lung cancers. Cancers. 2020;12(11):3343. doi:##Müller DC, Murtha AJ, Bacon JV, Stephenson M, Wells C, Vasquez-Rios C, et al. Prospective multicenter study of ctDNA versus tumor tissue guiding FGFR-targeted therapy in metastatic urothelial cancer. Nature Communications. 2026;17(1). doi:##Yi G, Luo H, Zheng Y, Liu W, Wang D, Zhang Y. Exosomal Proteomics: Unveiling Novel Insights into Lung Cancer. Aging and disease. 2024;16(2):876-900. doi:##Wu B, Yang X, Cai Y, Wan S, Liu J, Xing J, et al. Proteomic profiling of single extracellular vesicles as a promising new approach for the diagnosis and treatment modality of advanced ovarian cancer. npj Precision Oncology. 2026;10(1):65. doi:##Trouchet A, Gines G, Benhaim L, Taly V. Digital PCR: from early developments to its future application in clinics. Lab on a Chip. 2025;25(16):3921-61. doi:##Lin X, Zhou Y, Xue L. Mitochondrial complex I subunit MT-ND1 mutations affect disease progression. Heliyon. 2024;10(7):e28808. doi:##Cardoso GC, Ganzella FAO, Miniskiskosky G, da Cunha RS, Ramos EAS. Digital methylation-specific PCR: New applications for liquid biopsy. Biomol Concepts. 2024;15(1):20220041. doi:##Grossi I, Assoni C, Lorini L, Smussi D, Gurizzan C, Grisanti S, et al. Evaluation of DNA methylation levels of SEPT9 and SHOX2 in plasma of patients with head and neck squamous cell carcinoma using droplet digital PCR. Oncology reports. 2024;51(3):52. doi:##Jacobsen C, Oechsle K, Hauschild J, Steinemann G, Spath B, Bokemeyer C, et al. Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy. Thrombosis Research. 2015;136(3):673-81. doi:##Hisada Y, Sachetto ATA, Mackman N. Circulating tissue factor‐positive extracellular vesicles and their association with thrombosis in different diseases. Immunological Reviews. 2022;312(1):61-75. doi:##Zhu S, Li S, Yi M, Li N, Wu K. Roles of Microvesicles in Tumor Progression and Clinical Applications. International journal of nanomedicine. 2021;16:7071-90. doi:##Lacroix R, Vallier L, Bonifay A, Simoncini S, Mege D, Aubert M, et al. Microvesicles and Cancer Associated Thrombosis. Seminars in thrombosis and hemostasis. 2019;45(6):593-603. doi:##Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560(7718):382-6. doi:##Shimada Y, Matsubayashi J, Kudo Y, Maehara S, Takeuchi S, Hagiwara M, et al. Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer. Scientific reports. 2021;11(1):7830. doi:##De Gaetano A, Solodka K, Zanini G, Selleri V, Mattioli AV, Nasi M, et al. Molecular mechanisms of mtDNA-mediated inflammation. Cells. 2021;10(11):2898. doi:##Wen X, Fan J, Duan X, Zhu X, Bai J, Zhang T. Mitochondrial DNA in exercise-mediated innate immune responses. International Journal of Molecular Sciences. 2025;26(7):3069. doi:##Abadie JM. A Two-Genome Portrayal of Mitochondrial Disorders: A Review with Clinical Presentations. Front Biosci (Schol Ed). 2024;16(1):7. doi:##Liu Y, Ma X, Guan Q, Zhou S. Cell-free mitochondrial DNA (cf-mtDNA) in human body fluids: molecular characteristics, release mechanisms, and clinical translation—an updated review. Frontiers in molecular biosciences. 2026;13:1774015. doi:##Mehdi A, Rabbani SA. Role of methylation in pro-and anti-cancer immunity. Cancers. 2021;13(3):545. doi:##Dai E, Zhu Z, Wahed S, Qu Z, Storkus WJ, Guo ZS. Epigenetic modulation of antitumor immunity for improved cancer immunotherapy. Mol Cancer. 2021;20(1):171. doi:##Santana A, Roudiani N, Therrien J, Lee J, Felsen D, Carucci J. 104 Melanoma associated antigen A3 (MAGE-A3) influences proliferation of metastatic squamous cell carcinoma (SCC) in vitro. Journal of Investigative Dermatology. 2016;136(5):S19. doi:## ##

The Role of Stem Cells in Cardiac Tissue Repair After Myocardial Infarction: Physiological Mechanisms 2 2 Introduction: Myocardial infarction induces IRI, leading to cardiomyocyte necrosis, neutrophil-driven inflammation, and fibroblast-mediated fibrosis, culminating in ventricular dysfunction. Stem Cell such as MSCs promote angiogenesis via VEGF/HGF paracrine secretion; CPCs differentiate through Notch/Wnt for tissue replacement; iPSCs enable patient-specific remuscularization with Cx43 integration. Aim: The purpose of this study is to investigate the role of stem cells in cardiac tissue repair after myocardial infarction via physiological mechanisms. Discussion:  Stem cell–based therapies represent a promising yet evolving approach for cardiac repair following myocardial infarction. Preclinical models consistently demonstrate improvements in angiogenesis, attenuation of fibrosis, and partial restoration of ventricular function; however, these outcomes have not been fully replicated in clinical trials. Conclusion:  This review synthesizes mechanisms for advancing clinical translation. the future of cardiac regenerative medicine lies in the integration of mechanistic insights with bioengineering and molecular innovation. 10 18 2026/06/102025/12/24 1404/10/3 2026/06/162026/04/6 1405/1/17 AliReza pourrahim AliReza pourrahim student research committee,faculty of medicine,ilam university of medical sciences Iran Maryam Kheiry Maryam Kheiry Non-Communicable Diseases Research Center, Ilam University of Medical sciences, Ilam, Iran Iran m.kheiry@yahoo.com stem cells heart tissue Myocardial Infarction physiological mechanisms Xu Y, Wu S, Zhang L, Zhang M, Jiang Y. Cell death forms in myocardial ischemia-reperfusion injury and their potential clinical applications. Molecular and Cellular Biochemistry.2025:1-15.##Gao J, Li L, Zhai S, Dong Y, Zhang Z, Lin D, et al. Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice. International Journal of Molecular Medicine. 2025;56(5):191.##Guo M, Watanabe T, Shinoka T. Injectable Stem Cell-Based Therapies for Myocardial Regeneration: A Review of the Literature. Journal of Functional Biomaterials. 2025;16(5):152.##Ali SA, Mahmood Z, Mubarak Z, Asad M, Chaudhri MTS, Bilal L, et al. Assessing the Potential Benefits of Stem Cell Therapy in Cardiac Regeneration for Patients With Ischemic Heart Disease. Cureus. 2025;17(1).##Inouye K, White G, Khan S, Luba J, Benharash P, Thankam FG. Heart-derived endogenous stem cells. Molecular Biology Reports. 2025;52(1):1-13.##Cambria E, Steiger J, Günter J, Bopp A, Wolint P, Hoerstrup SP, et al. Cardiac regenerative medicine: the potential of a new generation of stem cells. Transfusion Medicine and Hemotherapy. 2016;43(4):275-81.##Moraddahande FM, Meybodi SME, Matin M, Soleimani N, Ghasemzadeh N, Firoozabadi AD. Current status and new horizons in stem cell therapy in cardiovascular regenerative medicine (CaVaReM): an update. European Journal of Medical Research. 2025;30(1):837.##Noorabadi P, Shahabi Rabori V, Jamali S, Jafari N, Saberiyan M. An overview on cardiac regeneration revolution: exploring the promise of stem cell therapies. Molecular Biology Reports. 2025;52(1):511.##Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. Journal of molecular and cellular cardiology. 2011;50(2):280-9.##Broughton KM, Wang BJ, Firouzi F, Khalafalla F, Dimmeler S, Fernandez-Aviles F, et al. Mechanisms of cardiac repair and regeneration. Circulation research. 2018;122(8):1151-63.##Collet BC, Davis DR. Mechanisms of cardiac repair in cell therapy. Heart, Lung and Circulation. 2023;32(7):825-35.##Terashvili M, Bosnjak ZJ. Stem cell therapies in cardiovascular disease. Journal of cardiothoracic and vascular anesthesia. 2019;33(1):209-22.##He L, Nguyen NB, Ardehali R, Zhou B. Heart regeneration by endogenous stem cells and cardiomyocyte proliferation: controversy, fallacy, and progress. Circulation. 2020;142(3):275-91.##Katarzyna R. Adult stem cell therapy for cardiac repair in patients after acute myocardial infarction leading to ischemic heart failure: an overview of evidence from the recent clinical trials. Current cardiology reviews. 2017;13(3):223-31.##Sun Q, Zhang Z, Sun Z. The potential and challenges of using stem cells for cardiovascular repair and regeneration. Genes & diseases. 2014;1(1):113-9. https://doi.org/ 10.1016/j.gendis.2014.07.003.##Tompkins BA, Balkan W, Winkler J, Gyöngyösi M, Goliasch G, Fernández-Avilés F, et al. Preclinical studies of stem cell therapy for heart disease. Circulation research. 2018;122(7):1006-20. https://doi.org/ 10.1161/CIRCRESAHA.117.312486.##Yu Y, Tham SK, Roslan FF, Shaharuddin B, Yong YK, Guo Z, et al. Large animal models for cardiac remuscularization studies: a methodological review. Frontiers in Cardiovascular Medicine. 2023;10:1011880. https://doi.org/ 10.3389/fcvm.2023.1011880.##Duran JM, Makarewich CA, Sharp TE, Starosta T, Zhu F, Hoffman NE, et al. Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms. Circulation research. 2013;113(5):539-52. https://doi.org/ 10.1161/CIRCRESAHA.113.301202.##Wan J, Lin S, Yu Z, Song Z, Lin X, Xu R, et al. Protective Effects of MicroRNA‐200b‐3p Encapsulated by Mesenchymal Stem Cells–Secreted Extracellular Vesicles in Myocardial Infarction Via Regulating BCL2L11. Journal of the American Heart Association. 2022;11(12):e024330. https://doi.org/ 10.1161/JAHA.121.024330.##Yue R, Lu S, Luo Y, Zeng J, Liang H, Qin D, et al. Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice. Cell death discovery. 2022;8(1):202. https://doi.org/ 10.1038/s41420-022-00909-6##Shao L, Zhang Y, Lan B, Wang J, Zhang Z, Zhang L, et al. MiRNA‐sequence indicates that mesenchymal stem cells and exosomes have similar mechanism to enhance cardiac repair. BioMed research international. 2017;2017(1):4150705. https://doi.org/ 10.1155/2017/4150705.##Wen Z, Huang W, Feng Y, Cai W, Wang Y, Wang X, et al. MicroRNA-377 regulates mesenchymal stem cell-induced angiogenesis in ischemic hearts by targeting VEGF. PLoS One. 2014;9(9):e104666. https://doi.org/ 10.1371/journal.pone.0104666.##Maries L, Marian C, Sosdean R, Goanta F, Sirbu IO, Anghel A. MicroRNAs—The Heart of Post-Myocardial Infarction Remodeling. Diagnostics. 2021;11(9):1675. https://doi.org/ 10.3390/diagnostics11091675.##Wang J, Huang W, Xu R, Nie Y, Cao X, Meng J, et al. Micro RNA‐24 regulates cardiac fibrosis after myocardial infarction. Journal of cellular and molecular medicine. 2012;16(9):2150-60. https://doi.org/ 10.1111/j.1582-4934.2012.01523.x##Li L, Bounds KR, Chatterjee P, Gupta S. Micro RNA‐130a, a potential antifibrotic target in cardiac fibrosis. Journal of the American Heart Association. 2017;6(11):e006763. https://doi.org/ 10.1161/JAHA.117.006763##Zhou Y, Richards AM, Wang P. MicroRNA-221 is cardioprotective and anti-fibrotic in a rat model of myocardial infarction. Molecular therapy Nucleic acids. 2019;17:185-97. https://doi.org/ 10.1016/j.omtn.2019.05.018##Ji X, Wu B, Fan J, Han R, Luo C, Wang T, et al. The anti-fibrotic effects and mechanisms of microRNA-486-5p in pulmonary fibrosis. Scientific reports. 2015;5(1):14131. https://doi.org/ 10.1038/srep14131##Du W, Liang H, Gao X, Li X, Zhang Y, Pan Z, et al. MicroRNA-328, a potential anti-fibrotic target in cardiac interstitial fibrosis. Cellular Physiology and Biochemistry. 2016;39(3):827-36. https://doi.org/ 10.1159/000447793##Huang X, Liang X, Han Q, Shen Y, Chen J, Li Z, et al. Pretreatment with growth differentiation factor 15 augments cardioprotection by mesenchymal stem cells in myocardial infarction by improving their survival. Stem Cell Research & Therapy. 2024;15(1):412. https://doi.org/ 10.1186/s13287-024-04030-6##Selvakumar D, Clayton ZE, Prowse A, Dingwall S, Kim SK, Reyes L, et al. Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. Nature Cardiovascular Research. 2024;3(2):145-65. https://doi.org/ 10.1038/s44161-023-00419-3##Fang Y-H, Wang SP, Chang H-Y, Yang P-J, Liu P-Y, Liu Y-W. Immunogenicity in stem cell therapy for cardiac regeneration. Acta Cardiologica Sinica. 2020;36(6):588. https://doi.org/ 10.6515/ACS.202011_36(6).20200811A##Lezmi E, Benvenisty N. The tumorigenic potential of human pluripotent stem cells. Stem Cells Translational Medicine. 2022;11(8):791-6. https://doi.org/ 10.1093/stcltm/szac039##Venegas-Zamora L, Fiedler M, Perez W, Altamirano F. Bridging the Translational Gap in Heart Failure Research: Using Human iPSC-derived Cardiomyocytes to Accelerate Therapeutic Insights. Methodist DeBakey Cardiovascular Journal. 2023;19(5):5. https://doi.org/ 10.14797/mdcvj.1295##Raziyeva K, Smagulova A, Kim Y, Smagul S, Nurkesh A, Saparov A. Preconditioned and genetically modified stem cells for myocardial infarction treatment. International journal of molecular sciences. 2020;21(19):7301. https://doi.org/ 10.3390/ijms21197301##Gil-Cabrerizo P, Scacchetti I, Garbayo E, Blanco-Prieto MJ. Cardiac tissue engineering for myocardial infarction treatment. European Journal of Pharmaceutical Sciences. 2023;185:106439. https://doi.org/ 10.1016/j.ejps.2023.106439##Akbar N, Razzaq SS, Salim A, Haneef K. Mesenchymal stem cell-derived exosomes and their MicroRNAs in heart repair and regeneration. Journal of Cardiovascular Translational Research. 2024;17(3):505-22. https://doi.org/ 10.1007/s12265-023-10449-8##Laforest B, Dai W, Tyan L, Lazarevic S, Shen KM, Gadek M, et al. Atrial fibrillation risk loci interact to modulate Ca 2+-dependent atrial rhythm homeostasis. The Journal of clinical investigation. 2019;129(11):4937-50. https://doi.org/ 10.1172/JCI124231##Tan X, Zhang J, Heng Y, Chen L, Wang Y, Wu S, et al. Locally delivered hydrogels with controlled release of nanoscale exosomes promote cardiac repair after myocardial infarction. Journal of Controlled Release. 2024;368:303-17. https://doi.org/ 10.1016/j.jconrel.2024.02.035## ##

Effects of Folate supplementation on the kidney in Streptozotocin-Induced Diabetic Rats 2 2 Introduction: Diabetes causes the body’s metabolic balance to be in disarray, which damages organs such as the kidneys due to their high metabolic activity. Tissue damage is caused by oxidative stress and chronic inflammation. Folate may help protect against diabetes complications by reducing oxidative stress, regulating homocysteine and supporting vascular and kidney health. Thus, this study was designed to investigate the effects of daily folate supplementation on glycaemic control, oxidative stress and renal dysfunction in streptozotocin-induced diabetic rats. Materials & Methods: Eighteen male Wistar rats were randomly divided into three groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin. The first group included healthy control rats, and the second included untreated diabetic rats. The third group received daily IP injections of folate for four weeks. Fasting blood glucose was measured using a glucometer. Oxidative stress was measured in the renal tissue and serum by determining the levels of malondialdehyde (MDA) and total oxidant status (TOS), respectively. Renal histopathological changes were examined by haematoxylin and eosin staining. The data were analysed using one-way ANOVA followed by Dunnett’s post hoc test. p < 0.05 was considered statistically significant. Results:  The results showed that folate reduced renal tissue MDA and serum triglyceride levels. Fasting blood glucose and serum TOS showed a decreasing trend, but the changes were not statistically significant. The tissue analysis showed slight improvements in kidney structure, but no full recovery was observed. Conclusion:  These data suggest that folate supplementation may provide some protection against renal injury due to diabetes. The effect on glycaemic control and full recovery of renal tissue appeared to be limited. These findings highlight the need for further studies to determine whether the combination of folate with other therapies could improve glycaemic control and promote tissue repair more effectively 19 29 2026/06/102025/12/242025/12/14 1404/9/23 2026/06/162026/04/62026/04/6 1405/1/17 Rahman Mohammadi Rahman Mohammadi Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran Akram Vatannejad Akram Vatannejad Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran vatannejad@ut.ac.ir Asma Kheirollahi Asma Kheirollahi Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran Sara Shokrpoor Sara Shokrpoor Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran AmirHossein RahimBakhsh AmirHossein RahimBakhsh Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran Tahmoures Sedighi Pashaki Tahmoures Sedighi Pashaki Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran Diabetes Oxidative stress Folate Kidney function Malondialdehyde 1. Federation, I.D. Diabetes facts & figures. 2025 7 Jun 2025]; Available from: https://idf.org/about-diabetes/diabetes-facts-figures/.##2. Xia, Z., et al., Long-term effectiveness of group-based diabetes self-management on glycosylated haemoglobin for people with type 2 diabetes in community: a protocol of systematic review and meta-analysis. BMJ Open, 2021. 11(6): p. e046692, https://doi.org/10.1136/bmjopen-2020-046692.##3. Galicia-Garcia, U., et al., Pathophysiology of type 2 diabetes mellitus. International journal of molecular sciences, 2020. 21(17): p. 6275, https://doi.org/10.3390/ijms21176275.##4. Triplitt, C.L., Understanding the kidneys' role in blood glucose regulation. American Journal of Managed Care, 2012. 18(1): p. S11.##5. Mima, A., Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. Journal of diabetes research, 2013. 2013(1): p. 248563, https://doi.org/10.1155/2013/248563.##6. Ogobuiro, I. and F. Tuma, Physiology, renal, in StatPearls [Internet]. 2023, StatPearls Publishing.##7. Horita, S., et al., The role of renal proximal tubule transport in the regulation of blood pressure. Kidney research and clinical practice, 2017. 36(1): p. 12, https://doi.org/10.23876/j.krcp.2017.36.1.12.##8. Caturano, A., et al., Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Current Issues in Molecular Biology, 2023. 45(8): p. 6651–6666, https://doi.org/10.3390/cimb45080420.##9. Parvathareddy, V.P., J. Wu, and S.S. Thomas, Insulin resistance and insulin handling in chronic kidney disease. Comprehensive Physiology, 2023. 13(4): p. 5069, https://doi.org/10.1002/j.2040-4603.2023.tb00281.x.##10. Frąk, W., et al., Role of uremic toxins, oxidative stress, and renal fibrosis in chronic kidney disease. Antioxidants, 2024. 13(6): p. 687, https://doi.org/10.3390/antiox13060687.##11. Vida, C., et al., Oxidative stress in patients with advanced CKD and renal replacement therapy: the key role of peripheral blood leukocytes. Antioxidants, 2021. 10(7): p. 1155, https://doi.org/10.3390/antiox10071155.##12. Jin, Q., et al., Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols. Frontiers in immunology, 2023. 14: p. 1185317, https://doi.org/10.3389/fimmu.2023.1185317.##13. Yanowsky-Escatell, F.G., et al., The role of dietary antioxidants on oxidative stress in diabetic nephropathy. Iranian journal of kidney diseases, 2020. 14(2), https://ijkd.org/index.php/ijkd/article/view/4984.##14. Mangoni, A.A., et al., Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. American journal of hypertension, 2005. 18(2): p. 220–226, https://doi.org/10.1016/j.amjhyper.2004.08.036.##15. RahimBakhsh, A., et al., Protective effects of S-adenosyl methionine on oxidative stress and tissue damage in STZ-induced diabetic rats. Amino acids, 2025. 57(1): p. 38, https://doi.org/10.1007/s00726-025-03471-4.##16. Furman, B.L., Streptozotocin‐induced diabetic models in mice and rats. Current protocols, 2021. 1(4): p. e78, https://doi.org/10.1002/cpz1.78.##17. Mutavdzin, S., et al., The effects of folic acid administration on cardiac oxidative stress and cardiovascular biomarkers in diabetic rats. Oxidative medicine and cellular longevity, 2019. 2019(1): p. 1342549, https://doi.org/10.1155/2019/1342549.##18. Shooshtari, M.K., A.A. Moazedi, and G.A. Parham, Memory and motor coordination improvement by folic Acid supplementation in healthy adult male rats. Iranian Journal of Basic Medical Sciences, 2012. 15(6): p. 1173, https://doi.org/10.22038/ijbms.2012.4937.##19. Yan, L., Folic acid-induced animal model of kidney disease. Animal Model Exp Med 4: 329–342. 2021, https://doi.org/10.1002/ame2.12194.##20. Zhang, L., et al., Folate reverses NF-κB p65/Rela/IL-6 level induced by hyperhomocysteinemia in spontaneously hypertensive rats. Frontiers in Pharmacology, 2021. 12: p. 651582, https://doi.org/10.3389/fphar.2021.651582.##21. Yang, C., et al., Folate-mediated one-carbon metabolism: a targeting strategy in cancer therapy. Drug Discovery Today, 2021. 26(3): p. 817–825, https://doi.org/10.1016/j.drudis.2020.12.006.##22. Schneider, M.P., et al., Effects of folic acid on renal endothelial function in patients with diabetic nephropathy: results from a randomized trial. Clinical Science, 2014. 127(7): p. 499–505, https://doi.org/10.1042/CS20140111.##23. Jing, Y. and Y. Chen, Folic Acid Protects Against Kidney Damage in Mice with Diabetic Nephropathy by Inhibiting M1 Macrophage Polarization via Nuclear Factor-k-gene Binding Pathway. Alternative Therapies in Health & Medicine, 2023. 29(6).##24. Ebaid, H., et al., Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress. Nutrition & metabolism, 2020. 17: p. 1–14, https://doi.org/10.1186/s12986-019-0419-7.##25. Liang, Y., et al., The association of metabolic profile of folate with diabetic kidney disease: evidence from 2011–2020 cycles of the NHANES. Renal Failure, 2024. 46(2): p. 2420830, https://doi.org/10.1080/0886022X.2024.2420830.##26. Tejchman, K., K. Kotfis, and J. Sieńko, Biomarkers and mechanisms of oxidative stress—last 20 years of research with an emphasis on kidney damage and renal transplantation. International journal of molecular sciences, 2021. 22(15): p. 8010, https://doi.org/10.3390/ijms22158010.##27. Asbaghi, O., et al., Effects of folic acid supplementation on oxidative stress markers: a systematic review and meta-analysis of randomized controlled trials. Antioxidants, 2021. 10(6): p. 871, https://doi.org/10.3390/antiox10060871.##28. Asbaghi, O., et al., Folic acid supplementation improves glycemic control for diabetes prevention and management: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutrients, 2021. 13(7): p. 2355, https://doi.org/10.3390/nu13072355.##29. Zhou, L., et al., Plasma homocysteine level is independently associated with conventional atherogenic lipid profile and remnant cholesterol in adults. Frontiers in Cardiovascular Medicine, 2022. 9: p. 898305, https://doi.org/10.3389/fcvm.2022.898305.##30. Fogacci, F., et al., Folic acid and plasma lipids: Interactions and effect of folate supplementation. Current Problems in Cardiology, 2024: p. 102539, https://doi.org/10.1016/j.cpcardiol.2024.102539.##31. Hirano, T., Pathophysiology of diabetic dyslipidemia. Journal of atherosclerosis and thrombosis, 2018. 25(9): p. 771–782, https://doi.org/10.5551/jat.RV17023.##32. Asbaghi, O., et al., Beneficial effects of folic acid supplementation on lipid markers in adults: A GRADE-assessed systematic review and dose-response meta-analysis of data from 21,787 participants in 34 randomized controlled trials. Critical Reviews in Food Science and Nutrition, 2022. 62(30): p. 8435–8453, https://doi.org/10.1080/10408398.2021.1928598.##33. Momin, M., et al., Relationship between plasma homocysteine level and lipid profiles in a community-based Chinese population. Lipids in health and disease, 2017. 16: p. 1–7, https://doi.org/10.1186/s12944-017-0441-6.##34. Nakai, K., et al., Streptozotocin induces renal proximal tubular injury through p53 signaling activation. Scientific Reports, 2023. 13(1): p. 8705, https://doi.org/10.1038/s41598-023-35850-w.##35. Slaughter, T.N., et al., Characterization of the development of renal injury in Type-1 diabetic Dahl salt-sensitive rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2013. 305(7): p. R727–R734, https://doi.org/10.1152/ajpregu.00382.2012.##36. Chtourou, Y., et al., Investigation of the renal protective effect of combined dietary polyphenols in streptozotocin-induced diabetic aged rats. Nutrients, 2022. 14(14): p. 2867, https://doi.org/10.3390/nu14142867.##37. Charlton, A., et al., Oxidative stress and inflammation in renal and cardiovascular complications of diabetes. Biology, 2020. 10(1): p. 18, https://doi.org/10.3390/biology10010018.##38. Wijerathne, C.U., K.K. Au-Yeung, and Y.L. Siow, 5-methyltetrahydrofolate attenuates oxidative stress and improves kidney function in acute kidney injury through activation of Nrf2 and antioxidant defense. Antioxidants, 2022. 11(6): p. 1046, https://doi.org/10.3390/antiox11061046.##39. Hamed, A.E., et al., Impact of folic acid supplementation on ischemia‒reperfusion-induced kidney injury in rats: folic acid prophylactic role revisited. The Journal of Physiological Sciences, 2024. 74(1): p. 7, https://doi.org/10.1186/s12576-024-00900-z.##40. Yan, L.J., Folic acid‐induced animal model of kidney disease. Animal models and experimental medicine, 2021. 4(4): p. 329–342, https://doi.org/10.1002/ame2.12194.## ##

Investigation of the Frequency of Congenital Metabolic Disorders in Children Referred to Bu-Ali Hospital in Ardabil During the Years 2016 to 2023 2 2 Introduction: Hereditary metabolic diseases are rare disorders individually, but in countries where family marriages are more common, such as Iran, they have a high prevalence, and in Ardabil Province, due to the fact that family and tribal marriages are more common, the prevalence of these disorders is higher. Since early diagnosis and follow-up treatment of these diseases are important to prevent irreparable damage, and on the other hand, these diseases involve different organs and have different clinical features. If the symptoms are detected, the complications, death, and disability of the disease will be prevented. Therefore, this study was decided to investigate the prevalence of congenital metabolic diseases in Ardabil province during the years 2016 to 2023. Materials & Methods: In this cross-sectional descriptive study, a total of 195 children (114 boys and 81 girls) aged 1-15 years at Bu-Ali Hospital of Ardabil city were registered with congenital metabolic diseases based on specific biochemical, genetic, and clinical criteria different from those for metabolic syndrome. The data were collected in a checklist and analyzed in SPSS V.21 using descriptive statistical methods in the form of tables, graphs, frequencies, and percentages. Results:  The overall prevalence of congenital metabolic disorders among the studied children was 3.3 per thousand people. The most common types of congenital metabolic disorders in the studied children were phenylketonuria with 62 cases (31.8%) and urea cycle disorders with 26 cases (13.3%). Conclusion:  In this study, more than 20 different types of hereditary metabolic disorders were identified among children, and more than 81% of the children's parents were related 30 37 2026/06/102025/12/242025/12/142025/07/20 1404/4/29 2026/06/162026/04/62026/04/62025/10/14 1404/7/22 Leyla Katebi Leyla Katebi Department of pediatrics, school of medicine, Ardabil University of medical sciences, aradabil, Iran Iran leyla.katebi1358@gmail.com Adel Ahadi Adel Ahadi Department of pediatrics, school of medicine, Ardabil University of medical sciences, aradabil, Iran Iran ahadiadel42@gmail.com Firouz Amani Firouz Amani Department of Community medicine and biostatistics, school of medicine, Ardabil University of medical sciences, aradabil, Iran Iran biostat.f@gmail.com congenital disorders children phenylketonuria Sewify M, Nair S, Warsame S, Murad M, Alhubail A, 1.Mirhosseini NA, Nadjarzadeh A, Golzar A, Fallah T, Sadri Z. Inborn Errors of Metabolism Referrals- Shahid Sadoughi Hospital: A Cross- Sectional Study. World J Peri & Neonatol. 2021;4(2):82–7.##Saudubray JM, Garcia-Cazorla À. Inborn Errors of Metabolism Overview: Pathophysiology, Manifestations, Evaluation, and Management. Pediatr Clin North Am. 2018 Apr;65(2):179–208.##Balakrishnan U. Inborn Errors of Metabolism-Approach to Diagnosis and Management in Neonates. Indian J Pediatr. 2021 Jul;88(7):679–89.##Yang CJ, Wei N, Li M, Xie K, Li JQ, Huang CG, et al. Diagnosis and therapeutic monitoring of inborn errors of metabolism in 100,077 newborns from Jining city in China. BMC Pediatr. 2018 Mar 13;18(1):110.##Luo H, Wang J, Chen J, Yi H, Yang X, Peng Y, et al. Prevalence of inherited metabolic disorders among newborns in Zhuzhou, a southern city in China. Front Genet. 2024;15:1197151.##Belaramani KM, Chan TCH, Hau EWL, Yeung MCW, Kwok AMK, Lo IFM, et al. Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey. Int J Neonatal Screen. 2024 Mar 11;10(1):23.##Hao L, Liang L, Gao X, Zhan X, Ji W, Chen T, et al. Screening of 1.17 million newborns for inborn errors of metabolism using tandem mass spectrometry in Shanghai, China: A 19-year report. Mol Genet Metab. 2024 Jan;141(1):108098.##Men S, Liu S, Zheng Q, Yang S, Mao H, Wang Z, et al. Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China. Mol Genet Genomic Med. 2023 Jun;11(6):e2152.##Zhu J, Han L, Yang P, Feng Z, Xue S. Spectrum analysis of inborn errors of metabolism for expanded newborn screening in Xinjiang, China. PeerJ. 2024 Dec 9;12:e18173.## ##

The Relationship of Thickness of the Subcutaneous Fat of the Anterior Abdominal Wall and the grade of Hepatic Steatosis 2 2 Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of fat buildup in the liver, which results in liver disease. This condition is becoming more commonplace worldwide. Knowing the causes of the disease is crucial for preventing and minimizing its effects, especially since the etiology of the condition is not fully understood. The aim of this study was to investigate the relationship between hepatic steatosis grading and the thickness of the subcutaneous fat of the anterior abdominal wall. Materials & Methods: In this descriptive cross-sectional study, all 181 patients underwent ultrasound scanning to determine the grade of their fatty liver, as well as to measure the thickness of the anterior abdominal wall's subcutaneous fat at the RUQ. The fatty liver grading was between 0 and 3. The questionnaire was filled out with the patient's height, weight, age, gender, fatty liver grade, thickness of subcutaneous fat, and underlying medical conditions. Results:  This study revealed that the distribution of hepatic steatosis among 47% of participants was normal (grade 0), while 42.5%, 9.4%, and 1.1% were classified as grade 1, grade 2, and grade 3 of fatty liver, respectively, as per ultrasonographic classification. Quantitative analysis of abdominal adiposity showed a mean anterior abdominal wall subcutaneous fat thickness of 16.31±6.45 mm. Crucially, subcutaneous fat thickness showed a significant positive correlation with hepatic steatosis grade (r = 0.39, p = 0.001), and each additional millimeter of fat thickness raised the likelihood of advanced steatosis. These results substantiate the clinical relevance of abdominal wall fat measurement as a potential surrogate marker for NAFLD severity. Conclusion:  The current study showed that more than half of patients had fatty liver in grades 1-3, and programming to change the lifestyle of people to avoid weight gain and manage NAFLD is necessary 38 47 2026/06/102025/12/242025/12/142025/07/202025/04/30 1404/2/10 2026/06/162026/04/62026/04/62025/10/142025/11/4 1404/8/13 Somayeh Zeynizadeh Jeddi Somayeh Zeynizadeh Jeddi Department of Radiology, School of medicine, Ardabil university of medical science, Ardabil, Iran. Iran s.zeynizadeh@arums.ac.ir Afshan Sharghi Afshan Sharghi Department of Community Medicine and Biostatistics, School of medicine, Ardabil university of medical science, Ardabil, Iran. Iran a.sharghi@gmail.com Sahand Ghorbani Davatgar Sahand Ghorbani Davatgar Department of Radiology, School of medicine, Ardabil university of medical science, Ardabil, Iran. Iran sahand.ghorbani@gmail.com Fatty Liver Subcutaneous Thickness Ultrasound Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.https://doi.org/ 10.1002/hep.28431.##Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397(10290):2212-2224.##Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-73.##Allen AM, Van Houten HK, Sangaralingham LR, Talwalkar JA, McCoy RG. Healthcare Cost and Utilization in Nonalcoholic Fatty Liver Disease: Real-World Data From a Large U.S. Claims Database. Hepatology. 2018;68(6):2230-38.##Ilyas F, Ali H, Patel P, Sarfraz S, Basuli D, Giammarino A, et al. Increasing nonalcoholic fatty liver disease-related mortality rates in the United States from 1999 to 2022. Hepatol Commun. 2023;7(7):e00207.##Friedman SL. Mechanisms of NAFLD development. Nat Med.2018;24(7):908-22. https://doi.org/ 10.1038/s41591-018-0104-9.##Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Diabetes Care. 2018;41(2):372-82.##Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54(3):1082-90.##Mustapic S, Ziga S, Matic V, Bokun T, Radic B, Lucijanic M, Marusic S, Babic Z, Grgurevic I. Ultrasound Grade of Liver Steatosis Is Independently Associated with the Risk of Metabolic Syndrome. Can J Gastroenterol Hepatol. 2018;2018:8490242.##Okanoue T, Umemura A, Yasui K, Itoh Y. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in Japan. J gastroenterolo hepatol.2011;26:153-62.##Kagansky N, Levy Sh, Keter D, Rimon E, Taiba Z,Fridman Z, et al. Non-alcoholic fatty liver disease–a common and benign finding in octogenarian patients. Liver Int. 2004;24(6):588-94.##Sweeny KF, Lee CK. Nonalcoholic Fatty Liver Disease in Children. Gastroenterol Hepatol (N Y). 2021;17(12):579-587.##Hashimoto E, Tokushige K. Prevalence, gender, ethnic variations, and prognosis of NASH. Journal of gastroenterology. 2011;46:63-69.##FAN JG, Zhu J, Li XJ, Chen L, Lu YS, Li L, et al. Fatty liver and the metabolic syndrome among Shanghai adults.J gastroenterol hepatol.2005;20(12):1825-32. https://doi.org/ 10.1111/j.1440-1746.2005.04058.x.##Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. Journal of hepatology. 2009;50(1):204-210.##Chiang DJ, Pritchard MT, Nagy LE. Obesity, diabetes mellitus, and liver fibrosis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2011;300(5):G697-G702.##Larson-Meyer DE, Heilbronn LK, Redman LM, Newcomer BR, Frisard MI, Anton S, et al. Effect of calorie restriction with or without exercise on insulin sensitivity, β-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes care. 2006;29(6):1337-44.##Stewart KJ, Bacher AC, Turner K, Lim JG,Hees PS, Shapiro EP, et al. Exercise and risk factors associated with metabolic syndrome in older adults. Am J Prev Med. 2005;28(1):9-18.##Rafiq N, Younossi ZM. Effects of weight loss on nonalcoholic fatty liver disease. Semin Liver Dis.2008;28(4)::427-33. https://doi.org/ 10.1055/s-0028-1091986.##Ueno T, Sugawara H, Sujaku K, et al. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. Journal of hepatology.1997;27(1):103-107. https://doi.org/ 10.1016/s0168-8278(97)80287-5.##Shah K, Stufflebam A, Hilton TN, Sinacore DR, Klein S, Villareal DT. Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. Obesity. 2009;17(12):2162-2168.##Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917-23.##Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. New England Journal of Medicine. 2010;363(14):1341-50.##Liu H, Lu H-Y. Nonalcoholic fatty liver disease and cardiovascular disease. World journal of gastroenterology: WJG. 2014;20(26):8407.##Perseghin G, Lattuada G, De Cobelli F, et al. Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver. Hepatology. 2008;47(1):51-8.##Okamoto M, Takeda Y, Yoda Y, Kobayashi K, Fujino MA, Yamagata Z. The association of fatty liver and diabetes risk. Journal of epidemiology. 2003;13(1):15-21.##Yamazaki H, Tsuboya T, Tsuji K, Dohke M, Maguchi H. Independent association between improvement of nonalcoholic fatty liver disease and reduced incidence of type 2 diabetes. Diabetes care. 2015;38(9):1673-79.##Salehi M, Islamivaghar M, Nasrabadi T. Evaluation of the relationship between fatty liver disease and diabetes in patients referred to hospitals affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran. Journal of Diabetes Nursing. 2016;4(2):25-39.##Yamada T, Fukatsu M, Suzuki S, Wada T, Yoshida T, Joh T. Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup. Journal of gastroenterology and hepatology. 2010;25(2):352-6.##Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124-31. https://doi.org/ 10.1053/j.gastro.2010.09.038.##Tohidi M, Harati H, Hadaege F, Mehrabi Y, Azizi F. Association of liver enzymes with incident type 2 diabetes: Tehran lipid and glucose study. Journal of Diabetes and Metabolic Disorders. 2007; 7:5-8.##Schmitz-Peiffer C. Signalling aspects of insulin resistance in skeletal muscle: mechanisms induced by lipid oversupply. Cellular signalling. 2000;12(9):583-94.##Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis.2008;28(4):339-50.##Liu CC, Hung CL, Shih SC, Ko HJ, Lu YT, Wu YJ, et al. Age-related Differences in the Clinical Presentation, Associated Metabolic Abnormality, and Estimated Cardiovascular Risks from Nonalcoholic Fatty Liver Disease: A Cross-sectional Study from Health Evaluation Center in Taiwan. International Journal of Gerontology.2010;4(4):184-91.##Fukuda K, Seki Y, Ichihi M, Okada T, Hirata A, Kogita S, et al. Usefulness of ultrasonographic estimation of preperitoneal and subcutaneous fat thickness in the diagnosis of nonalcoholic fatty liver disease in diabetic patients. Journal of Medical Ultrasonics. 2015;42:357-63.##Liu K, Chan Y, Chan J, Chan W, Kong W. Mesenteric fat thickness as an independent determinant of fatty liver. International journal of obesity.2006;30(5):787-93.## ##

Comparison of Weaning Success from Mechanical Ventilation Using Heat and Moisture Exchangers (HME) and Humidifier in Intensive Care Unit (ICU) Patients: A Quasi-Experimental Study 2 2 Introduction: Weaning a patient from mechanical ventilation is an important step in the treatment of patients admitted to the intensive care unit, the failure of which can be associated with adverse effects in patients. Thus, the present study was conducted with the aim of determining and comparing the success rate in the process of weaning a patient from mechanical ventilation using heat and moisture exchangers (HME) and a humidifier in patients admitted to the intensive care unit (ICU). Materials & Methods: In this quasi-experimental study, 40 patients treated with mechanical ventilation in the intensive care unit of hospitals of Ilam (Iran) were evaluated by random sampling in two intervention groups of 20 with HME and humidifier filters. In the first group, humidification of inhaled air was used using a humidifier filter, and in the second group, an HME filter was used to humidify inhaled air. Data related to the process of weaning patients from mechanical ventilation before and after the intervention were recorded in a checklist and analyzed by STATA V.12 using descriptive and inferential statistical tests in the significance less than 0.05. Results:  The rate of successful weaning was higher in the humidifier group (65%) compared with the HME group (40%), whereas weaning failure occurred in 35% and 60% of patients, respectively. Patients in the humidifier group showed a lower rate of weaning failure compared with the HME group; however, this association was not statistically significant in the adjusted analysis (OR = 0.40, P = 0.23). The PaO2/FiO2 ratio measured 30 minutes before weaning from mechanical ventilation was significantly associated with successful weaning (P = 0.003), such that each unit increase in this ratio reduced the odds of weaning failure by 3%. Conclusion:  Given the higher success rate of the humidifier filter compared to the HME in weaning patients from mechanical ventilation, the humidifier filter may be considered as a potential option for weaning from mechanical ventilation in patients admitted to the intensive care unit, though further research is needed to confirm its efficacy 48 59 2026/06/102025/12/242025/12/142025/07/202025/04/302025/12/6 1404/9/15 2026/06/162026/04/62026/04/62025/10/142025/11/42026/02/24 1404/12/5 Mohammadreza Bastami Mohammadreza Bastami Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Iran bastami@yahoo.com Fakhredin Taghinezhad Fakhredin Taghinezhad Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Iran taghynejad@yahoo.com Arman Azadi Arman Azadi Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Iran azadi-a@medilam.ac.ir Hamid Heidarzadeh Hamid Heidarzadeh Department of Medical-Surgical Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Iran motmot19981377@gmail.com Masoumeh Nouri Masoumeh Nouri Student Research Committee, Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Iran masoomehnoori1381@gmail.com Maryam Pakseresht Maryam Pakseresht Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Iran pakseresht-m@medilam.ac.ir Success Weaning Mechanical Ventilation Patient Heat and Moisture Exchangers (HME) Humidifier Burja S, Belec T, Bizjak N, Mori J, Markota A, Sinkovič A. Efficacy of a bundle approach in preventing the incidence of ventilator associated pneumonia (VAP). Bosn J Basic Med Sci. 2018;18(1):105-109.##Jang CS, Shin YS. Effects of combination oral care on oral health, dry mouth and salivary PH of intubated patients: a randomized controlled trial. Int J Nurs Pract. 2016;22(5):503-511.##Shi Y, Wang Y, Cai M, Zhang B, Zhu J. An aviation oxygen supply system based on a mechanical ventilation model. Chin J Aeronaut. 2018;31(1):197-204.##Cason C, Tyner T, Saunders S, Broome L. Nurses' implementation of guidelines for ventilator-associated pneumonia from the Centers for Disease Control and Prevention. Am J Crit Care. 2017;16(1):28-36.##Morton SE, Docherty J, Chase JG, Docherty P, Desaive T, Howe SL, Shaw GM, Tawhai M. A virtual patient model for mechanical ventilation. Comput Methods Programs Biomed. 2018;165:77-87.##Vargas M, Chiumello D, Sutherasan Y, et al. Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) in adult critically ill patients: a systematic review, meta-analysis and meta-regression of randomized controlled trials. Crit Care. 2017;21:123.##Lellouche F, Qader S, Taille S, Lyazidi A, Brochard L. Influence of ambient temperature and moisture ventilation on passive and active heat and moisture exchange. Respir Care. 2014;59(5):637-643.##Roquilly A, Cinotti R, Jaber S, Vourc’h M, Pengam F, Mahe PJ, et al. Implementation of an evidence-based extubation readiness bundle in 499 brain-injured patients: a before-after evaluation of a quality improvement project. Am J Respir Crit Care Med. 2013;188(8):958-966.##Strøm T. A protocol of no sedation for critically ill patients receiving mechanical ventilation. 50 Studies Every Intensivist Should Know. 2018;33:1-10.##Borges LGA, Savi A, Teixeira C, de Oliveira RP, De Camillis MLF, Wickert R, et al. Mechanical ventilation weaning protocol improves medical adherence and results. J Crit Care. 2017;41:296-302.##Stawicki SP. Mechanical ventilation: weaning and extubation. Int J Acad Med. 2017;3(3):67-71.##Pittenuzzo T, Fan E. 2016 year in review: mechanical ventilation. Respir Care. 2017;62(5):629-635.##McBeth CL, Montes RS, Powne A, North SE, Natale JE. Interprofessional approach to the sustained reduction in ventilator-associated pneumonia in a pediatric intensive care unit. Crit Care Nurse. 2018;38(6):36-45.##Metcalf AY, Stoller JK, Fry TD, Habermann M. Patterns and factors associated with respiratory care protocol use. Respir Care. 2015;60(5):636-643.##Bench S. Humidification in the long-term ventilated patient: a systematic review. Intensive Crit Care Nurs. 2003;19(2):75-84.##Hess DR, Kallstrom TJ, Mottram CD, et al. Care of the ventilator circuit and its relation to ventilator-associated pneumonia. Respir Care. 2003;48(9):869-879.##Siempos II, Vardakas KZ, Kopterides P, Falagas ME. Impact of passive humidification on clinical outcomes of mechanically ventilated patients: a meta-analysis of randomized controlled trials. Crit Care Med. 2007;35(12):2843-2851.##Burns SM, Fisher C, Tribble SS, Lewis R, Merrel P, Conaway MR, et al. The relationship of 26 clinical factors to weaning outcome. Am J Crit Care. 2012;21(1):52-58.##Keykha A, Khoshfetrat M, Dahmardeh AR, Dashipour A, Dahmardeh M, Sarhadi A. Success rate of weaning from mechanical ventilation in patients admitted to the intensive care unit with utilization Burn’s Wean Assessment Program. Arch Anesthesiol Crit Care. 2017;3(2):319-323.##Salmani F. The effect of discontinuation protocol on the duration of mechanical ventilation. Iran J Nurs (IJN). 2013;26(82):62-73.##Mabrouk A, Mansour OF, Abdel Aziz AA, Elhabashy MM, Alasdoudy AA. Evaluation of some predictors for successful weaning from mechanical ventilation. Egypt J Chest Dis Tuberc. 2015;64(4):703-707.##Basiri R, Malekzadeh J, Derogar M, Mazloom R. Comparison between CROP and Rapid Shallow Breathing Index as predictors of weaning in predicting the outcome of discontinuation from mechanical ventilation in ICU patients. Med J Mashhad Univ Med Sci. 2018;61(1):825-835.##Schreiber AF, Ceriana P, Ambrosino N, Piran M, Malovini A, Carlucci A. Short-term effects of an active heat-and-moisture exchanger during invasive ventilation. Respir Care. 2019;64(10):1215-1221.##MacIntyre NR, Epstein SK, Carson S, Scheinhorn D, Christopher K, Muldoon S. Management of patients requiring prolonged mechanical ventilation: report of a NAMDRC consensus conference. Chest. 2005;128(6):3937-3954.##Appendini L, Patessio A, Zanaboni S, Carone M, Spada E, Gukov B, et al. Partitioning of inspiratory muscle workload and pressure assistance in ventilator-dependent COPD patients. Am J Respir Crit Care Med. 1996;154(5):1301-1309.##Lellouche F, Maggiore SM, Deye N, Taillé S, Pigeot J, Harf A, Brochard L. Effect of the humidification device on the work of breathing during noninvasive ventilation. Intensive Care Med. 2002;28(11):1582-1589.##Pelosi P, Solca M, Selmo G, Corradini M, Chiaranda M, Novario R, Park GR. In vitro evaluation of an active heat-and-moisture exchanger: the Hygrovent Gold. Respir Care. 2010;55(4):460-466.##Campbell RS, Davis K Jr, Johannigman JA, Branson RD. The effects of passive humidifier dead space on respiratory variables in paralyzed and spontaneously breathing patients. Respir Care. 2000;45(3):306-312.##Jaber S, Chanques G, Matecki S, Ramonatxo M, Souche B, Perrigault PF, Eledjam JJ. Comparison of the effects of heat and moisture exchangers and heated humidifiers on ventilation and gas exchange during non-invasive ventilation. Intensive Care Med. 2002;28(11):1590-1594.##Tu CS, Chang CH, Chang SC, Lee CS, Chang CT. A decision for predicting successful extubation of patients in intensive care unit. Biomed Res Int. 2018;2018:6820975.##El Khoury MY, Piraino T, Rodriguez P, Ying J, Almoosa KF. Value of the PaO2/FiO2 ratio and Rapid Shallow Breathing Index in predicting successful extubation in hypoxemic respiratory failure. Heart Lung. 2010;39(6):529-536.##Furqan A, Rai SA, Ali L, Ahmed RA. Comparing the predicted accuracy of PO2/FIO2 ratio with rapid shallow breathing index for successful spontaneous breathing trial in intensive care unit. Pak J Med Sci. 2019;35(6):1605-1610.##Keykha A, Khoshfetrat M, Dahmardeh AR, Dashipour A, Dahmardeh M, Sarhadi A. Success rate of weaning from mechanical ventilation in patients admitted to the intensive care unit with utilization Burn’s Wean Assessment Program. Arch Anesthesiol Crit Care. 2017;3(2):319-323.##Abin M, Shiri Qidari P, Hanifi N, Faqihzadeh S. The comparative evaluation of active and passive humidifiers on ventilator-associated pneumonia. Prev Care Nurs Midwifery J. 2018;7(4):57-63.##Virole SD, Morawiec E, Nierat MC, Paifait M, Decavele M, Demoule A, Delemazure J, Dres M. Contribution and evolution of respiratory muscles function in weaning outcome of ventilator-dependent patients. Crit Care. 2024;28:421.##Warnke C, Heinze A, Müller-Heinrich A, Knaak C, Friesecke S, Obst A, Bollmann T, Desole S, Boesche M, Stubbe B, et al. Predictors of survival after prolonged weaning from mechanical ventilation. J Crit Care. 2020;60:212-217.##Saber H, Mai M, Kazemlou S, Navi BB, Yoo AJ, Simonsen CZ, Sandio A, Rajah G, Khatibi K, Liebeskind DS, et al. Prevalence, predictors, and outcomes of prolonged mechanical ventilation after endovascular stroke therapy. Neurocrit Care. 2021;34:1009-1016.##Pham T, Brochard LJ, Slutsky AS, Bellani G, Madotto F, Aragao I, Beduneau G, Goligher EC, Grasselli G, Laake JH, et al. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN-SAFE): a multicentre, prospective, observational cohort study. Lancet Respir Med. 2023;11(5):465-476.##Béduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, Grelon F, Runge I, Terzi N, Grangé S, et al. Epidemiology of weaning outcome according to a new definition. The WIND study. Am J Respir Crit Care Med. 2017;195(6):772-783.##Windisch W, Dellweg D, Geiseler J, Westhoff M, Pfeifer M, Suchi S, Schönhofer B. Prolonged weaning from mechanical ventilation. Dtsch Arztebl Int. 2020;117(12):197-204.##Amir B, Mai O, Shira T, Ido P, Nave P, Carmi B. Predictors of weaning success in patients on prolonged mechanical ventilation: a retrospective cohort study. J Clin Med. 2025;14(13):4427.##Nadir OT, Oğuzülgen IK, et al. The clinical and microbiological comparison of the use of heated humidifiers and heat and moisture exchanger filters with booster in mechanically ventilated patients. Tuberk Toraks. 2009;57(3):259-267.## ##

Biochemical and Biological Properties of Curcumin and its Association with Carbohydrate Metabolism: A Review Article 2 2 Introduction: Carbohydrates, popularly known as sugars, are one of three major macromolecules essential for the functioning of living organisms. Altered carbohydrate metabolism can lead to the development of type 2 diabetes mellitus (T2DM). Uncontrolled blood glucose in T2DM is a risk factor for several serious complications, including cardiovascular and cerebrovascular disease, nephropathy, retinopathy, and neuropathy. Synthetic pharmaceuticals are often used by subjects with T2DM to reduce these risks. However, natural compounds from plants might be good candidates for enhancing carbohydrate metabolism and for the improvement of glycemic control. Discussion: The present study was aimed at assessing the biochemical and biological properties of curcumin with special reference to carbohydrate metabolism. Results:  Curcumin is the yellow pigment and the most important bioactive component of turmeric, which is obtained from the rhizomes of this medicinal plant. It has unique biological and structural features and variable bioavailability. The positive physiological effects of curcumin depend on the dose and the time of administration. Recently, curcumin nanoformulations have been proposed as novel therapeutic modalities to improve their bioavailability and clinical efficacy. Curcumin has structural properties that allow it to penetrate cells easily and exert beneficial metabolic effects by improving insulin secretion and sensitivity via modulation of glucagon-like peptide-1 (GLP-1), lipid metabolism, and inflammatory signaling pathways. Preclinical studies and randomized controlled trials (RCTs) have shown that curcumin is significantly associated with pathways involved in carbohydrate metabolism. Conclusion:  The available evidence suggests that curcumin may significantly improve carbohydrate metabolism and glycemic control in patients with type 2 diabetes mellitus. Curcumin, with its antioxidant, anti-inflammatory, and insulin-sensitizing properties, may be a promising natural therapeutic agent for the management of impaired glucose metabolism. But we need large clinical trials to prove that it works in the long run, at the right dose, and is safe 60 72 2026/06/102025/12/242025/12/142025/07/202025/04/302025/12/62025/08/30 1404/6/8 2026/06/162026/04/62026/04/62025/10/142025/11/42026/02/242026/04/6 1405/1/17 Ali Nosrati Andevari Ali Nosrati Andevari Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran Iran nosrati.ali70@gmail.com Najmeh Ebrahimzadeh Shahandashti Najmeh Ebrahimzadeh Shahandashti Department of Medical Laboratory Science, Babol Branch, Islamic Azad University, Babol, Iran Iran najme8287@gmail.com Mohsen Koolivand Mohsen Koolivand Royan Stem Cell Technology Company, Tehran, Iran Iran mkoolivand14@gmail.com Faegheh Bahri Faegheh Bahri Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran Iran faegheh.bahri9797@gmail.com Rana Douseh Rana Douseh Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran Iran ranadooseh@gmail.com Durdi Qujeq Durdi Qujeq Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran Iran dqujeq@gmail.com Curcumin Turmeric Carbohydrate Glycemic T2DM Preclinical RCT Niaz K, Khan F, Shah MA. Analysis of carbohydrates (monosaccharides, polysaccharides). Recent advances in natural products analysis: Elsevier; 2020. p. 621-33.##Manfredi AP, Pisa JH, Valdeón DH, Perotti NI, Martínez MA. Synergistic effect of simple sugars and carboxymethyl cellulose on the production of a cellulolytic cocktail from Bacillus sp. AR03 and enzyme activity characterization. Applied Biochemistry and Biotechnology. 2016;179:16-32.##Andevari AN, Moein S, Qujeq D, Moazezi Z, Hajian-Tilaki K. The Effects of Atorvastatin Consumption on Biochemical Variables in Patients with Type 2 Diabetes Mellitus and Pre-diabetes. International Journal of Medical Laboratory. 2022.##Andevari AN, Moein S, Qujeq D, Moazezi Z, Tilaki KH. Effects of atrovastatin on concentrations of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase (HMG-CoA-R), proprotein convertase subtilisin/kexin type 9 (PCSK9) and sortilin in patients with type 2 diabetes mellitus and pre-diabetics. Journal of Nephropathology. 2020;10(1):e05-e. https://doi.org/ 10.34172/jnp.2021.05.##Andevari AN, Moein S, Qujeq D, Moazezi Z, Tilaki KH. The effect of atorvastatin on the concentrations of methylglyoxal, glyoxalase 1, and aldo–keto reductase family 1 member B10 in patients with type 2 diabetes mellitus and prediabetes. International Journal of Diabetes in Developing Countries. 2024;44(2):400-8.##6. Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nature reviews Disease primers. 2019;5(1):41.##Andevari AN, Firoozjaee AH, Meftah N, Asciabari HA, Bahri F, Shahandashti NE, et al. The effects of atorvastatin consumption on blood levels of sortilin, glycemic, and lipid indices in type 2 diabetic patients: A randomized clinical trial. International Journal of Diabetes in Developing Countries. 2025:1-8.##Abd El‐Hack ME, El‐Saadony MT, Swelum AA, Arif M, Abo Ghanima MM, Shukry M, et al. Curcumin, the active substance of turmeric: its effects on health and ways to improve its bioavailability. Journal of the Science of Food and Agriculture. 2021;101(14):5747-62.##Feng J-Y, Liu Z-Q. Phenolic and enolic hydroxyl groups in curcumin: which plays the major role in scavenging radicals? Journal of agricultural and food chemistry. 2009;57(22):11041-6.##Kocaadam B, Şanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Critical reviews in food science and nutrition. 2017;57(13):2889-95.##Patra D, El Kurdi R. Curcumin as a novel reducing and stabilizing agent for the green synthesis of metallic nanoparticles. Green Chemistry Letters and Reviews. 2021;14(3):474-87.##Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE, Rimbach G. Curcumin—from molecule to biological function. Angewandte Chemie International Edition. 2012;51(22):5308-32.##Klawitter M, Quero L, Klasen J, Gloess AN, Klopprogge B, Hausmann O, et al. Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity. Journal of Inflammation. 2012;9:1-14. http://www.journal inflammation.com/content/9/1/29.##Kharat M, Du Z, Zhang G, McClements DJ. Physical and chemical stability of curcumin in aqueous solutions and emulsions: impact of pH, temperature, and molecular environment. Journal of agricultural and food chemistry. 2017;65(8):1525-32.##Syed HK, Liew KB, Loh GOK, Peh KK. Stability indicating HPLC–UV method for detection of curcumin in Curcuma longa extract and emulsion formulation. Food Chemistry. 2015;170:321-6.##Zhu J. Curcumin and its oxidative degradation products: their comparative effects on inflammation. 2016. https://doi.org/ 10.7275/8433277.##Niu Y, Ke D, Yang Q, Wang X, Chen Z, An X, et al. Temperature-dependent stability and DPPH scavenging activity of liposomal curcumin at pH 7.0. Food Chemistry. 2012;135(3):1377-82.##Wu Y, Mou B, Song S, Tan C-P, Lai O-M, Shen C, et al. Curcumin-loaded liposomes prepared from bovine milk and krill phospholipids: Effects of chemical composition on storage stability, in-vitro digestibility and anti-hyperglycemic properties. Food Research International. 2020;136:109301.##Saikeaw R, Bijaisoradat O, Netcharoensirisuk P, Dubas ST. Improved pH sensing of curcumin loaded polyelectrolyte multilayers thin films. Sensor Letters. 2016;14(6):572-6.##Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Molecular pharmaceutics. 2007;4(6):807-18.##Sabet S, Rashidinejad A, Melton LD, McGillivray DJ. Recent advances to improve curcumin oral bioavailability. Trends in Food Science & Technology. 2021;110:253-66.##Gera M, Sharma N, Ghosh M, Lee SJ, Min T, Kwon T, et al. Nanoformulations of curcumin: an emerging paradigm for improved remedial application. Oncotarget. 2017;8(39):66680. https://doi.org/ 10.18632/oncotarget.19164.##Hafez Ghoran S, Calcaterra A, Abbasi M, Taktaz F, Nieselt K, Babaei E. Curcumin-based nanoformulations: A promising adjuvant towards cancer treatment. Molecules. 2022;27(16):5236.##Gorgani L, Mohammadi M, Najafpour GD, Nikzad M. Piperine—the bioactive compound of black pepper: from isolation to medicinal formulations. Comprehensive reviews in food science and food safety. 2017;16(1):124-40.##Askari G, Sahebkar A, Soleimani D, Mahdavi A, Rafiee S, Majeed M, et al. The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial. Trials. 2022;23(1):472.##Soliman G. Effect of curcumin, mixture of curcumin and piperine and curcum (turmeric) on lipid profile of normal and hyperlipidemic rats. The Egyptian Journal of Hospital Medicine. 2005;21(1):145-61. https://doi.org/ 10.21608/ejhm.2005.18057.##Hosseini H, Bagherniya M, Sahebkar A, Iraj B, Majeed M, Askari G. The effect of curcumin‐piperine supplementation on lipid profile, glycemic index, inflammation, and blood pressure in patients with type 2 diabetes mellitus and hypertriglyceridemia. Phytotherapy Research. 2024;38(11):5150-61.##Hoehle SI, Pfeiffer E, Sólyom AM, Metzler M. Metabolism of curcuminoids in tissue slices and subcellular fractions from rat liver. Journal of agricultural and food chemistry. 2006;54(3):756-64.##Schalkwijk CG, Micali LR, Wouters K. Advanced glycation endproducts in diabetes-related macrovascular complications: focus on methylglyoxal. Trends in Endocrinology & Metabolism. 2023;34(1):49-60.##Brunham LR, Kruit JK, Pape TD, Timmins JM, Reuwer AQ, Vasanji Z, et al. β-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nature medicine. 2007;13(3):340-7. https://doi.org/ 10.1038/nm1546.##Zhang C, Xiang D, Zhao Q, Jiang S, Wang C, Yang H, et al. Curcumin nicotinate decreases serum LDL cholesterol through LDL receptor-mediated mechanism. European Journal of Pharmacology. 2022;931:175195.##Singh L, Sharma S, Xu S, Tewari D, Fang J. Curcumin as a natural remedy for atherosclerosis: a pharmacological review. Molecules. 2021;26(13):4036.##Barrientos G, Sánchez-Aguilera P, Jaimovich E, Hidalgo C, Llanos P. Membrane cholesterol in skeletal muscle: a novel player in excitation‐contraction coupling and insulin resistance. Journal of diabetes research. 2017;2017(1):3941898.##Marquez VE, Blumberg PM. Synthetic diacylglycerols (DAG) and DAG-lactones as activators of protein kinase C (PK-C). Accounts of chemical research. 2003;36(6):434-43.##Gupta A, Behl T, Sehgal A, Bhardwaj S, Singh S, Sharma N, et al. Exploring the recent molecular targets for diabetes and associated complications. Molecular Biology Reports. 2021;48:2863-79.##Su L-q, Chi H-y. Effect of curcumin on glucose and lipid metabolism, FFAs and TNF-α in serum of type 2 diabetes mellitus rat models. Saudi journal of biological sciences. 2017;24(8):1776-80.##Wang P, Su C, Feng H, Chen X, Dong Y, Rao Y, et al. Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice. International journal of immunopathology and pharmacology. 2017;30(1):25-43.##Semova I, Levenson AE, Krawczyk J, Bullock K, Gearing ME, Ling AV, et al. Insulin prevents hypercholesterolemia by suppressing 12α-hydroxylated bile acids. Circulation. 2022;145(13):969-82.##Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, et al. Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PloS one. 2012;7(1):e28784.##Bassaganya-Riera J, Misyak S, Guri AJ, Hontecillas R. PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation. Cellular immunology. 2009;258(2):138-46.##Razmpoosh E, Safi S, Nadjarzadeh A, Salehi-Abargouei A, Mazaheri M, Mirmiran P, et al. Effects of Nigella sativa supplementation on blood concentration and mRNA expression of TNF-α, PPAR-γ and adiponectin, as major adipogenesis-related markers, in obese and overweight women: a crossover, randomised-controlled trial. British Journal of Nutrition. 2023;129(4):627-36.##Tahri-Joutey M, Andreoletti P, Surapureddi S, Nasser B, Cherkaoui-Malki M, Latruffe N. Mechanisms mediating the regulation of peroxisomal fatty acid beta-oxidation by PPARα. International journal of molecular sciences. 2021;22(16):8969.##Zheng F, Cai Y. Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet. Lipids in Health and Disease. 2019;18:1-8.##Zhao N-J, Liao M-J, Wu J-J, Chu K-X. Curcumin suppresses Notch-1 signaling: improvements in fatty liver and insulin resistance in rats. Molecular Medicine Reports. 2018;17(1):819-26.##Demir EA, Tutuk O, Dogan-Gocmen H, Ozyilmaz DS, Karagul MI, Kara M, et al. CREB1 and PPAR-α/γ Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection. Iranian Journal of Pharmaceutical Research: IJPR. 2023;21(1):e133779. https://doi.org/ 10.5812/ijpr-133779.##Gao S, Zhou J, Liu N, Wang L, Gao Q, Wu Y, et al. Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13. Journal of molecular and cellular cardiology. 2015;85:131-9.##Kim JH, Park JM, Kim EK, Lee JO, Lee SK, Jung JH, et al. Curcumin stimulates glucose uptake through AMPK‐p38 MAPK pathways in L6 myotube cells. Journal of Cellular Physiology. 2010;223(3):771-8. .##Wang Z, Xu D, She L, Zhang Y, Wei Q, Aa J, et al. Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice. Molecular and cellular endocrinology. 2018;474:127-36.##Fujiwara H, Hosokawa M, Zhou X, Fujimoto S, Fukuda K, Toyoda K, et al. Curcumin inhibits glucose production in isolated mice hepatocytes. Diabetes research and clinical practice. 2008;80(2):185-91.##Tahapary DL, Pratisthita LB, Fitri NA, Marcella C, Wafa S, Kurniawan F, et al. Challenges in the diagnosis of insulin resistance: focusing on the role of HOMA-IR and Tryglyceride/glucose index. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2022;16(8):102581.##Vladu IM, Forțofoiu M, Clenciu D, Forțofoiu M-C, Pădureanu R, Radu L, et al. Insulin resistance quantified by the value of HOMA-IR and cardiovascular risk in patients with type 2 diabetes. Experimental and therapeutic medicine. 2022;23(1):73.##Huang J, Guan B, Lin L, Wang Y. Improvement of intestinal barrier function, gut microbiota, and metabolic endotoxemia in type 2 diabetes rats by curcumin. Bioengineered. 2021;12(2):11947-58.##Thota RN, Rosato JI, Dias CB, Burrows TL, Martins RN, Garg ML. Dietary supplementation with curcumin reduce circulating levels of glycogen synthase kinase-3β and islet amyloid polypeptide in adults with high risk of type 2 diabetes and Alzheimer’s disease. Nutrients. 2020;12(4):1032.##Yaikwawong M, Jansarikit L, Jirawatnotai S, Chuengsamarn S. Curcumin extract improves beta cell functions in obese patients with type 2 diabetes: A randomized controlled trial. Nutrition Journal. 2024;23(1):119.##Karandish M, Mozaffari‐khosravi H, Mohammadi SM, Cheraghian B, Azhdari M. The effect of curcumin and zinc co‐supplementation on glycemic parameters in overweight or obese prediabetic subjects: A phase 2 randomized, placebo‐controlled trial with a multi‐arm, parallel‐group design. Phytotherapy Research. 2021;35(8):4377-87.##Mokhtari M, Razzaghi R, Momen‐Heravi M. The effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial. Phytotherapy Research. 2021;35(4):2099-107.##Tomas E, Habener JF. Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis. Trends in Endocrinology & Metabolism. 2010;21(2):59-67. https://doi.org/ 10.1016/j.tem.2009.11.007.##Kato M, Nishikawa S, Ikehata A, Dochi K, Tani T, Takahashi T, et al. Curcumin improves glucose tolerance via stimulation of glucagon‐like peptide‐1 secretion. Molecular Nutrition & Food Research. 2017;61(3):1600471.##Seo KI, Choi MS, Jung UJ, Kim HJ, Yeo J, Jeon SM, et al. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Molecular nutrition & food research. 2008;52(9):995-1004.##Ding L, Li J, Song B, Xiao X, Zhang B, Qi M, et al. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway. Toxicology and applied pharmacology. 2016;304:99-109.##Uzokov J, Alyavi B, Payziev D, Abdullaev A, Muxitdinova O. Influence of diet with low glycemic index on pro-inflammatory cytokines in patients with metabolic syndrome and coronary artery disease. Atherosclerosis. 2021;331:e250. https://doi.org/ 10.1016/j.atherosclerosis.2021.06.764.##Andevari AN, Qujeq D. Anti-inflammatory Mechanisms Beyond Cholesterol-Lowering Capabilities of Statins: Evidence from in vitro and in vivo Studies. Advances in Pharmacology and Therapeutics Journal. 2025.##Palideh A, Vaghari-Tabari M, Andevari AN, Qujeq D, Asemi Z, Alemi F, et al. MicroRNAs and Periodontal Disease: Helpful Therapeutic Targets? Advanced Pharmaceutical Bulletin. 2022;13(3):423. https://doi.org/ 10.34172/apb.2023.048.##Zamanian MY, Alsaab HO, Golmohammadi M, Yumashev A, Jabba AM, Abid MK, et al. NF‐κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation. Cell Biochemistry and Function. 2024;42(4):e4030.##Moghaddam NSA, Oskouie MN, Butler AE, Petit PX, Barreto GE, Sahebkar A. Hormetic effects of curcumin: What is the evidence? Journal of cellular physiology. 2019;234(7):10060-71.##Soetikno V, Sari FR, Sukumaran V, Lakshmanan AP, Harima M, Suzuki K, et al. Curcumin decreases renal triglyceride accumulation through AMPK–SREBP signaling pathway in streptozotocin-induced type 1 diabetic rats. The Journal of nutritional biochemistry. 2013;24(5):796-802.##Heshmati J, Moini A, Sepidarkish M, Morvaridzadeh M, Salehi M, Palmowski A, et al. Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial. Phytomedicine. 2021;80:153395.##Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S. Curcumin extract for prevention of type 2 diabetes. Diabetes care. 2012;35(11):2121-7.##Cicero AF, Sahebkar A, Fogacci F, Bove M, Giovannini M, Borghi C. Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non-alcoholic fatty liver disease indices: a double-blind, placebo-controlled clinical trial. European journal of nutrition. 2020;59:477-83.##Ghanbarzadeh-Ghashti N, Ghanbari-Homaie S, Shaseb E, Abbasalizadeh S, Mirghafourvand M. The effect of Curcumin on metabolic parameters and androgen level in women with polycystic ovary syndrome: a randomized controlled trial. BMC Endocrine Disorders. 2023;23(1):40.##Pourhabibi‐Zarandi F, Rafraf M, Zayeni H, Asghari‐Jafarabadi M, Ebrahimi AA. Effects of curcumin supplementation on metabolic parameters, inflammatory factors and obesity values in women with rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled clinical trial. Phytotherapy Research. 2022;36(4):1797-806.##He Y, Chen X, Li Y, Liang Y, Hong T, Yang J, et al. Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: A randomized controlled trial. The American Journal of Clinical Nutrition. 2024;120(1):66-79.##Jamilian M, Foroozanfard F, Kavossian E, Aghadavod E, Shafabakhsh R, Hoseini A, et al. Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Clinical nutrition ESPEN. 2020;36:128-33.##Hellmann PH, Bagger JI, Carlander KR, Forman J, Chabanova E, Svenningsen JS, et al. The effect of curcumin on hepatic fat content in individuals with obesity. Diabetes, Obesity and Metabolism. 2022;24(11):2192-202.##Rahmani S, Asgary S, Askari G, Keshvari M, Hatamipour M, Feizi A, et al. Treatment of non‐alcoholic fatty liver disease with curcumin: A randomized placebo‐controlled trial. Phytotherapy Research. 2016;30(9):1540-8.##Chuengsamarn S, Rattanamongkolgul S, Phonrat B, Tungtrongchitr R, Jirawatnotai S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: a randomized controlled trial. The Journal of nutritional biochemistry. 2014;25(2):144-50.##Shafabakhsh R, Asemi Z, Reiner Ž, Soleimani A, Aghadavod E, Bahmani F, et al. The effects of nano-curcumin on metabolic status in patients with diabetes on hemodialysis, a randomized, double blind, placebo-controlled trial. Iranian Journal of Kidney Diseases. 2020;14(4).## ##

The Relationship Between Knowledge, Attitude, And Preventive Practices Towards Respiratory Viral Infections and Quality of Life in Medical Sciences Students: A Descriptive-Correlational Study 2 2 Introduction: Respiratory infections affect millions worldwide, and preventive practices are essential for their control. The relationship between knowledge, attitude, and preventive practices (KAP) towards respiratory viral infections and quality of life (QoL) among medical sciences students was investigated in this study. Materials & Methods: A descriptive-correlational study with 535 participants from Shahid Sadoughi University in 2021. Data were collected using a demographic questionnaire, the SF-12 quality-of-life scale, and a KAP (knowledge, attitude, and preventive practices) questionnaire. Data were analysed with SPSS 20.0 using independent t-tests, Kruskal-Wallis tests, and Spearman’s correlation at a significance level of 0.05. Results:  The results showed significant positive correlations among knowledge, attitude, and preventive practice scores (p < 0.001). However, no significant association was found between these variables and quality of life (p = 0.528, p = 0.354, and p = 0.977, respectively). Students with higher economic status reported significantly better quality of life compared to others (p = 0.003). Conclusion:  While medical students demonstrated good KAP, targeted interventions are needed to enhance practices and improve QoL, particularly among economically disadvantaged groups. 73 83 2026/06/102025/12/242025/12/142025/07/202025/04/302025/12/62025/08/302025/01/6 1403/10/17 2026/06/162026/04/62026/04/62025/10/142025/11/42026/02/242026/04/62025/09/20 1404/6/29 Fatemeh Fathi Fatemeh Fathi BSc in Nursing, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran fatemeh.fathi1378@gmail.com Ahmad Reza Fallahfaraghe Ahmad Reza Fallahfaraghe BSc in Nursing, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran ahmadreza.fallahfaraghe1928@gmail.com Mohammad Adham Mohammad Adham BSc in Nursing, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran mohammad.adham1999@gmail.com Fahimeh Shojaeifar Fahimeh Shojaeifar Nursing and Midwifery Care Research Center, Maternal and Child Health Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran fahimehshojaefar@yahoo.com attitude knowledge practice quality of life respiratory infections Khomich, O.A., et al., Redox Biology of Respiratory Viral Infections. Viruses, 2018. 10(8):392.##Kim, S.J., Relationship between nurses’ knowledge of COVID-19, professional quality of life, and practice during the COVID-19 pandemic: A descriptive correlational study. PLoS One. 2023. 18(6):e0287457.##Tripathi, R., et al., Awareness and preparedness of COVID-19 outbreak among healthcare workers and other residents of South-West Saudi Arabia: a cross-sectional survey. Front Public Health. 2020;8:482.##Wu, Z. and J.M.J.j. McGoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.##Fallahi, A., et al., Public knowledge, attitude and practice regarding home quarantine to prevent COVID-19 in Sabzevar city, Iran. J Mil Med. 2020;22(6):580-8.##Lotfi, M., M.R. Hamblin, and N.J.C.c.a. Rezaei, COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta. 2020;508:254-66.##Glanz, K., B.K. Rimer, and K. Viswanath, Health behavior and health education: Theory, research, and practice. 4th ed. San Francisco: John Wiley & Sons; 2008.##Puspitasari, I.M., et al., Knowledge, attitude, and practice during the COVID-19 pandemic: a review. J Multidiscip Healthc. 2020;13:727-33.##Adab, Z., et al., Dormitory student's Knowledge and Attitude about influenza a (H1N1) disease. Rahavard Salamat Journal, 2016. 2(2):10-17.##Taghrir, M.H., R. Borazjani, and R. Shiraly, COVID-19 and Iranian medical students; a survey on their related-knowledge, preventive behaviors and risk perception. Archives of Iranian medicine, 2020. 23(4):249-254.##Wassif, G.O. and D.A.G. El Din, Relationship between knowledge, attitude, and practice of COVID-19 precautionary measures and the frequency of infection among medical students at an Egyptian University. PLoS One. 2022;17(9):e0274473.##Heidari-Soureshjani, R., et al., The relationship between health-related quality of life of students at Tehran University of Medical Sciences and their knowledge, attitudes, and practices regarding COVID-19 in 2020. Journal of Education and Health Promotion, 2022. 11:64.##El Keshky, M.E.S., S.S. Basyouni, and A.M. Al Sabban, Getting through COVID-19: The pandemic’s impact on the psychology of sustainability, quality of life, and the global economy–A systematic review. Frontiers in Psychology, 2020. 11: 585897.##Kharshiing, K.D., et al., Quality of life in the COVID-19 pandemic in India: Exploring the role of individual and group variables. Community mental health journal, 2021. 57(1):70-78.##Kisvetrová, H., et al., Predictors of quality of life and attitude to ageing in older adults with and without dementia. Aging & mental health, 2021. 25(3):535-542.##Amiri, M., et al., A study of the life quality of students at a university of medical sciences in the northeast of Iran. Journal of Knowledge & Health, 2014. 8(4):176.##Afra, A., et al., The study of the relationship between quality of life and health literacy among Students of Abadan Faculty of Medical Sciences. Journal of Nursing Education (JNE), 2019. 8(1):54-60.##Nasirzadeh, M. and M. Aligol, Assessmentof knowledge, attitude, and factors associated with the preventive behaviors of COVID-19 in Qom, Iran, in 2020. Qom Univ Med Sci J, 2020. 14(7):50-7.##Ware, J.E., M. Kosinski, and S.D. Keller, A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Medical care, 1996. 34(3):220-233.##Montazeri, A., et al., The Iranian version of 12-item Short Form Health Survey (SF-12): factor structure, internal consistency and construct validity. BMC public health, 2009. 9(1): 341.##Ranjbar Roghani, A., et al., Knowledge and attitude for medical students towards COVID-19. Iran Journal of Nursing, 2020. 33(126):44-57.##Rahmanian, M., et al., Knowledge, Attitude and Practice of Students of Jahrom University of medical sciences to the new coronavirus (Covid-19). Medical journal of mashhad university of medical sciences, 2020. 63(3): 2359-2369.##Larebo, Y.M. and D.E. Abame, Knowledge, attitudes, and practices of face mask utilization and associated factors in COVID-19 pandemic among Wachemo University Students, Southern Ethiopia: A cross-sectional study. PloS one, 2021. 16(9):e0257609.##Saadat, S.H., S. Shahyad, and M.M. Asadi, Predicting the rate of preventive behaviors based on levels of exposure to COVID-19, risk perception and COVID-19 anxiety in students and staff of Military University of Medical Sciences: A cross-sectional study. Journal of Marine Medicine, 2021. 3(4):57-64.##Shakiba, E., F. Abolhadi, and M. Sadeghi, Assessing the quality of academic life of medical and dental students of Rafsanjan University of Medical Sciences in the corona epidemic. 2021.548-556.## ##