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Applications of phytomedicines in cardiovascular regeneration therapy: pre-clinical and clinical studies 2 2 Cardiovascular diseases (CVDs) are the leading cause of death in human societies. Several medicinal and interventional therapeutic approaches are approved for the treatment of CVDs, one of which is phytomedicine. Phytomedicine is described as the exploitation of the therapeutic properties of herbal medicines. The cardioprotective effects of phytochemicals are due to their anti-oxidative, anti-hypercholesterolemia, anti-inflammatory, antiangiogenic, and anti ischemic activities, reducing the risk factors of developing CVDs. Regenerative medicine (RM) is a well-established f ield that aims to replace, repair, and regenerate diseased and injured human cells, tissues, or organs. Stem cells’ (SC) potential to differentiate into various cell types and their self-renewal capabilities have made them an excellent tool for applying RM in CVD. The intersection of phytomedicines and regenerative medicine can be categorized into two main areas. Phytochemicals have been shown to significantly enhance the proliferation and differentiation of mesenchymal stem cells (MSCs). For example, certain plant extracts promote osteogenic (bone-forming) and chondrogenic (cartilage-forming) differentiation of MSCs, thereby enhancing stem cell function. Additionally, plant derived compounds can mitigate the side effects associated with conventional therapies while offering effective treatment options for tissue regeneration (natural alternatives to traditional therapeutics). This paper reviews current evidence and studies on the beneficial properties of phytomedicines in cardiac RM, both in animal models and in humans. In summary, all of the mentioned studies suggestthat the use of phytomedicine may be directly or indirectly involved in cardiogenesis and angiogenesis by stimulating endogenous SCs and their secretory activity, modulating cytokine release, signal transduction, and elevating the levels of several cardiac regeneration factors. On the other hand, various mechanisms through which these herbal medicines act, such as reducing oxidative stress, controlling inflammation, and promoting angiogenesis, underscore their potential as viable alternatives or adjuncts to conventional therapies for cardiovascular diseases. The integration of phytomedicine into clinical practice could lead to enhanced overall therapeutic efficacy, more effective and personalized treatment, fewer cardiovascular risks and better health outcomes. Further research is required to elucidate the specific molecular pathways through which phytomedicines exert their beneficial effects on cardiac tissue. Understanding these mechanisms will help in developing targeted therapies. 350 374 2024/03/17 1402/12/27 2025/02/17 1403/11/29 Mohammad Sheibani Mohammad Sheibani Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Iran mohammadsheibani89@gmail.com Maryam Shayan Maryam Shayan Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran maryamshayan99@gmail.com Afrooz Mohammadgholi-Beiki Afrooz Mohammadgholi-Beiki Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Iran afrooz.beygi@gmail.com Amin Sharifi Amin Sharifi German Heart Centre Munich, Department of Cardiology, Technical University of Munich, Munich, Germany Germany amin.sharifi@tum.de Majid Jafari-Sabet Majid Jafari-Sabet Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Iran jafarisabet.m@iums.ac.ir Ali Mohammad Sharifi Ali Mohammad Sharifi Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Iran sharifalim@gmail.com Phytomedicine Regenerative medicine Stem cells Mesenchymal stem cells Cardiac regeneration Angiogenesis Alaribe F N, Motaung K S C M. 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Serum levels of thyroid hormones change differently in the onset and progress phases of the experimental model of Parkinson’s disease in rats 2 2 Introduction: Changes in the levels of serum components can help in the early and differential diagnosis of Parkinson’s disease (PD). The lesion in the dopaminergic (DAergic) system is the main pathophysiological mechanism underlying PD. This system is closely related to the hypothalamic-pituitary-thyroid axis. Here, we examined the impact of PD onset, progress, and severity in rats on the serum levels of thyroid hormones (THs). Methods: The neurotoxin 6-OHDA was injected into the medial forebrain bundle. Behavioral tests were carried out for eight weeks after the toxin to assess the severity of PD and its progress. Blood was collected before the toxin and in the third and eighth weeks afterward. THs levels were determined using specific ELISA kits. Results: Our findings show that the THs levels changed significantly after the toxin. The levels of T3 and T4 decreased slightly in the third week but remarkably increased in the eighth week. The decrease in the third week depended on the severity of the PD and was observed only in the rats with severe behavioral symptoms. On the other hand, the increase in the eighth week occurred in all 6-OHDA-received rats with severe or mild behavioral symptoms. Conclusion: Our data indicate that serum levels of THs may decrease and increase in PD. At the onset of the disease, the levels may decrease if DAergic neuronal death is severe. In the progress phase of PD, THs levels may increase independent of the severity of the disease. 375 385 2024/03/172024/07/21 1403/4/31 2025/02/172025/05/7 1404/2/17 Shahram Darabi Shahram Darabi Non-communicable Diseases Research Center, Research Institute for prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran Iran shahram2005d@yahoo.com Hashem Haghdoost- Yazdi Hashem Haghdoost- Yazdi Non-communicable Diseases Research Center, Research Institute for prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran Iran hhaghdoost@qums.ac.ir Mohammad Sofiabadi Mohammad Sofiabadi Non-communicable Diseases Research Center, Research Institute for prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran Iran mohasofi@yahoo.com Mohammad Hossein Esmaeili Mohammad Hossein Esmaeili Non-communicable Diseases Research Center, Research Institute for prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran Iran esmail66@yahoo.com Mehrdad Delashoob Mehrdad Delashoob Non-communicable Diseases Research Center, Research Institute for prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran Iran physician_Mehrdad@outlook.com Parkinson’s disease Thyroid hormones 6-OHDA Onset Progress Adani G, Filippini T, Michalke B, Vinceti M. Selenium and other trace elements in the etiology of Parkinson’s disease: a systematic review and meta-analysis of case-control studies. Neuroepidemiology 2020; 54 (1) :1-23.##Bay A A, Hart A R, Michael Caudle W, Corcos D M, Hackney M E. The association between Parkinson’s disease symptom side-of-onset and performance on the MDS-UPDRS scale part IV: Motor complications. Journal of the Neurological Sciences 2019; 15:396:262-265.##Chan Y K, Davis P F, Poppitt S D, Sun X, Greenhill N S, Krishnamurthi R, et al., Influence of tail versus cardiac sampling on blood glucose and lipid profiles in mice. Laboratory Animals 2012; 46(2):142-147.##Chaudhuri K R, Schapira A H. Non-motor symptom of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurology 2009; 8(5):464-474.##Chen S F, Yang Y C, Hsu C Y, Shen Y C. Risk of Parkinson’s disease in patients with hypothyroidism: A nationwide populatio n-based cohort study. Parkinsonism and Related Disorders 2020; 74: 28-32.##Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron 2003; 39 (6), 889-909.##Duval F, Mokrani M C, Danila V, Erb A, Gonzalez Lopera F, Tomsa M. Dopamine function and hypothalamic-pituitary-thyroid axis activity in major depressed patients with suicidal behavior. Brain Sci 2022;12(5):621.##Gupta A, Haboubi N, Thomas P. Screening for thyroid dysfunction in the elderly. Archives of Internal Medicine 2001;161(1):130.##Haghdoost-Yazdi H, Hosseini S S, Faraji A, Nahid D, Jahanihashemi H. 2010. Long term exposure to norharmane exacerbates 6-hydroxydopamine-induced parkinsonism: possible involvement of L-type Ca2+ channels. Behavioural Brain Research 2010; 215 (1): 136-140.##Hassan W A, Aly M S, Rahman T A, Shahat A S. Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats. International Journal of Developmental Neuroscience 2013; 31(4): 225-33.##Hernandez-Baltazar D, Zavala-Flores L M, Villanueva-Olivo A. The 6-hydroxydopamine model and parkinsonian pathophysiology: novel findings in an older model. Neurologia. 2017; 32(8):533-539.##Iancu R, Mohapel P, Brundin P, Paul G. 2005. Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson’s disease in mice. Behavioural Brain Research 2005; 162(1): 1-10.##Davies J S, Morrish P K, Scanlon M F. Graves’ disease presenting as hemiparkinsonism. Journal of Endocrinological Investigation 2001; 24(3): 188-189.##Kim H T, Edwards M J, Lakshmi Narsimhan R, Bhatia K P. Hyperthyroidism exaggerating parkinsonian tremor: a clinical lesson. Parkinsonism and Related Disorders 2005; 11(5):331-332.##Kimber J, Watson L, Mathias C J. Neuroendocrine responses to levodopa in multiple system atrophy (MSA). Movement Disorders. 1999;14(6):981-987. https://doi.org/10.1002/1531-8257(199911)14:63.0.CO;2-W##Krulich L, Giachetti A, Marchlewska-Koj A, Hefco E, Jameson H E. On the role of the central noradrenergic and dopaminergic systems in the regulation of TSH secretion in the rat. Endocrinology 1977; 100: 496-505.##Menezes E C, Santos P R, Goes T C, Carvalho V C B, Teixeira-Silva F, Stevens H E, et al. Effects of a rat model of gestational hypothyroidism on forebrain dopaminergic, GABAergic, and serotonergic systems and related behaviors. Behavioural Brain Research 2019; 366: 77-87.##Minaei A, Haghdoost-Yazdi H. Dexmedetomidine attenuates the induction and reverses the progress of 6-hydroxydopamine- induced parkinsonism; involvement of KATP channels, alpha 2 adrenoceptors and anti-inflammatory mechanisms. Toxicology and Applied Pharmacology 2019; 1:382:114743.##Minaei A, Sarookhani MR, Haghdoost-Yazdi H, Rajaei F. Hydrogen sulfide attenuates induction and prevents progress of the 6-hydroxydopamine-induced Parkinsonism in rat through activation of ATP-sensitive potassium channels and suppression of ER stress. Toxicology and Applied Pharmacology 2021; 15:423:115558.##Nicola S, Surmeir J, Malemka R. Dopaminergic modulation of neuronal excitability in the striatum and nucleus acumbens. Annual Review of Neuroscience 2000; 23:185-215.##Ocak O, Sahin E M, Cam M. the relationship of thyroid hormone levels and motor symptoms in Parkinson’s disease. Duzce Medical Journal 2022; 24(2): 142-146.##Oetting A. Yen P M. New insights into thyroid hormone action. Best Pract Res Clin Endocrinol Metab 2007; 21(2): 193-208.##Pereira J C Jr, Pradella-Hallinan M, Lins Pessoa Hd. Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis. Clinics (Sao Paulo) 2010; 65(5):548-54.##Piri H, Sharifi S, Nigjeh S, Haghdoost-Yazdi H. Dopaminergic neuronal death in the substantia nigra associates with change in serum levels of TNF-α and IL-1β; evidence from early experimental model of Parkinson’s disease. Neurological Research 2022; 44(6):544-553.##Przegaliński E, Jaworska L, Budziszewska B. The role of dopamine receptors in the release of thyrotropin-releasing hormone from the rat striatum and nucleus accumbens: An in vitro study. Neuropeptides 1993; 25: 277-282.##Reich S G, Savitt J M. Parkinson’s disease. Medical Clinics of North America 2019; 103(2):337-350.##Rodrigues S F, de Oliveira M A, Martins J O, Sannomiya P, de Cássia Tostes R, Nigro D, Fortes Z B. Differential effects of chloral hydrate- and ketamine/xylazine-induced anesthesia by the s.c. route. Life Science 2006; 79:1630 -1637.##Rye D B, Freeman A A H. Dopamine in Behavioral State Control, in Monti J M, Pandi-Perumal S R, and Sinton CM, editors: Neurochemistry of Sleep and Wakefulness. Cambridge University Press, Cambridge, 2008. 179-223.##Saha J K, Xia J, Grondin J M, Engle S K, Jakubowski J A. Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models. Experimental Biology and Medicine (Maywood, N.J.) 2005; 230:777-784.##Scanlon M F, Weightman D R, Shale D J, Mora B, Heath M, Snow M H, et al. Dopamine is a physiological regulator of thyrotrophin (TSH) secretion in normal man. Clin. Endocrinology 1979; 10: 7-15.##Shulman J M, De Jager P L, Feany M B. Parkinson’s disease: genetics and pathogenesis. Annual Review of Pathology 2011; 6:193-222.##Tandeter H, Levy A, Gutman G, Shvartzman P. Subclinical thyroid disease in patients with Parkinson’s disease. Arch Gerontol Geriatr 2001; 33(3): 295-300.##Trupp M, Jonsson P, Ohrfelt A, Zetterberg H, Obudulu O, Malm L, et al. Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson’s disease. Journal of Parkinson’s Disease 2014; 4(3): 549-560.##Umehara T, Matsuno H, Toyoda C, Oka H. Thyroid hormone level is associated with motor symptoms in de novo Parkinson’s disease. Journal of Neurology 2015; 262(7):1762-1768.##Wang Z, Yang Y, Xiang X, Zhu Y, Men J, He M, et al., Estimation of the normal range of blood glucose in rats. Journal of hygiene research 2010; 39(2):133-7.##Wei Z, Li X, Li X, Liu Q, Cheng Y. Oxidative stress in Parkinson’s disease: a systematic review and meta-analysis. Frontiers in Molecular Neuroscience 2018; 11:236.##Yuan H, Sarre S, Ebinger G, Michotte Y. Histological, behavioral and neurochemical evaluation of medial forebrain bundle and striatal 6-OHDA lesions as rat models of Parkinson’s disease. Journal of Neuroscience Methods 2005; 144 (1), 35-45.## ##

Co-administration of hydro-alcoholic Teucrium polium l. extract and glibenclamide on pancreatic islets in streptozotocin-induced diabetic rats- a stereological analysis 2 2 Introduction: As herbal drugs have the potential to influence the therapeutic outcomes of pharmaceutical drugs, we investigated the effects of co-administration of Teucrium polium L. extract (TP) and Glibenclamide (Glib) on pancreatic islets in diabetic rats. Methods: Male Wistar rats were separated into six distinct groups (n=8). The control and sham control (normal saline), while four diabetic rats received different treatments (normal saline, Glib (5mg/kg), TP (200mg/kg), or co-administration of TP and Glib), via gavage, for 6 weeks. Induction of diabetes was performed with Streptozotocin injection, intraperitoneally at a dose of 55 mg/kg. The animals were anesthetized, and their dissected pancreases were fixed in 10% Formalin. Stereological assessments were done to determine pancreas volume, islet volume, volume density of islets relative to the pancreas, and the number of beta and apoptotic cells within the islets. Ultimately, the data analysis was conducted using SPSS and ANOVA. Results: Histological examinations revealed that the administration of TP, Glib, and their co administration did not non-significantly increase the islet volume and volume density of islets relative to the pancreas in diabetic rats. However, treatment with these drugs led to an increase in the number of beta-cells and a decrease in the number of apoptotic cells within the islet. Notably, co-administration of these drugs did not yield significant differences compared to individual treatments. Conclusion: This study demonstrates that TP and Glib have similar impacts in streptozotocin induced diabetic rats. Co-administration of the two agents did not lead to a statistically significant difference compared with either treatment alone. 386 397 2024/03/172024/07/212024/09/10 1403/6/20 2025/02/172025/05/72025/02/16 1403/11/28 Ghasem Sazegar Ghasem Sazegar Department of Occupational Therapy, Faculty of Paramedicine and Rehabilitation, Mashhad University of Medical Sciences, Mashhad, Iran Iran Sazegargh@mums.ac.ir Ali Akbar Rajabzadeh Ali Akbar Rajabzadeh Department of Anatomical Sciences, School of Medicine, Babol University of Medical Sciences, Babol, Iran Iran aa.rajabzadeh@mubabol.ac.ir Maryam Paseban Maryam Paseban Department of Medical Basic Sciences, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran Iran maryampaseban1400@gmail.com Hoda Khoshdel- Sarkarizi Hoda Khoshdel- Sarkarizi Department of Medical Basic Sciences, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran Iran khoshdelhoda@gmail.com Diabetes Teucrium polium Glibenclamide Pancreas Stereology Akinlolu A A, Salau B A, Ekor M, Otulana J. Musa sapientum with exercises attenuates hyperglycemia and pancreatic islet cells degeneration in alloxan-diabetic rats. Journal of Intercultural Ethnopharmacology 2015; 4: 202.##Alreshidi M, Noumi E, Bouslama L, Ceylan O, Veettil V N, Adnan M, et al. Phytochemical screening, antibacterial, antifungal, antiviral, cytotoxic, and anti-quorum-sensing properties of Teucrium polium L. aerial parts methanolic extract. Plants 2020; 9: 1418.##Ardestani A, Yazdanparast R, Jamshidi S. Therapeutic effects of Teucrium polium extract on oxidative stress in pancreas of streptozotocin-induced diabetic rats. Journal of Medicinal Food 2008; 11: 525-532.##Asghari A A, Mokhtari-Zaer A, Niazmand S, Mc Entee K, Mahmoudabady M. Anti-diabetic properties and bioactive compounds of Teucrium polium L. Asian Pacific. Journal of Tropical Biomedicine 2020; 10: 433-441.##Ashrafihelan J, Yazdanparast R, Esmaeili M, Nowrozi M. 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Aerobic training and royal jelly enhance thermogenesis genes in the visceral adipose tissue of high-fat diet-induced obese rats 2 2 Introduction: The crucial role of adipose tissue (AT) in energy balance has sparked significant interest in researching this tissue as a potential target for obesity treatment. Exercise and dietary interventions are promising strategies for addressing obesity. This study aimed to examine the impact of aerobic training and royal jelly on the expression of thermogenesis-related genes in the visceral adipose tissue (VAT) of obese rats. Methods: Rats (n=45) were divided into five groups: normal diet (ND), high-fat diet (HFD), high-fat diet-training (HFDT), high-fat diet-royal jelly (HFDRJ), and high-fat diet-training royal jelly (HFDTRJ). Royal jelly treatment was administered at a dosage of 100 mg/kg body weight. The training was conducted at an intensity of 50-60% VO2max, five days a week for eight weeks. Thermogenesis gene expression was evaluated by the real-time PCR method. Results: Induction of an HFD significantly reduced the expression of UCP-1, PRDM16, and CREB-1 compared to the normal diet (ND) group (p=0.001). Aerobic training and RJ significantly increased the levels of UCP-1, PRDM16 and CREB-1 in the VAT of HFD rats (p=0.0001). The combined intervention of aerobic training with RJ had no significant effect on the levels of UCP-1, PRDM16 and CREB-1 in the VAT of HFD rats. Conclusion: It appears that aerobic training and RJ are effective methods for positively regulating the gene expression related to thermogenesis in AT, which may mitigate obesity induced by a high-fat diet. 398 407 2024/03/172024/07/212024/09/102024/09/5 1403/6/15 2025/02/172025/05/72025/02/162025/04/8 1404/1/19 Ahmad Abdi Ahmad Abdi Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran Iran a.abdi58@gmail.com Exercise Obesity Royal jelly UCP-1 PRDM16 CREB-1 Altarejos J Y, Montminy M. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nature Reviews Molecular Cell Biology 2011; 12: 141-151.##Bartelt A, Bruns O T, Reimer R, Hohenberg H, Ittrich H, Peldschus K, et al. Brown adipose tissue activity controls triglyceride clearance. Nature Medicine 2011; 17: 200-205.##Bi P, Shan T, Liu W, Yue F, Yang X, Liang X-R, et al. Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. 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Evaluation of the effect of biodegradable dressing prepared from chitosan and external microvesicles of Bifidobacterium bifidum on burn wound healing in male Wistar rats 2 2 Introduction: The burn wound healing process is multi-variable, and various factors are involved. Chitosan-based dressings are acceptable materials for wound healing. PProbiotics and postbiotics can in-crease the effectiveness of these dressings. This study aimed to investigate the effect of a biodegradable dressing prepared from chitosan and external microvesicles of Bifidobacterium bifidum on burn wound healing in male Wistar rats. Methods: Bifidobacterium bifidum was cultured, the activated crude supernatant (ACS) was separated, and the microvesicles were isolated with the help of Ultra-centrifugation at 150,000×g at 4°C for 30 minutes. Chitosan films containing and without microvesicles were prepared using a heater stirrer at 29°C. The effectiveness of the membranes was evaluated. For this purpose, 60 male rats with second-degree burns were randomly divided into 5 groups (n=12) and were treated for 21 days. The process of wound healing was examined macroscopically and microscopically (wound histology and evaluation of gene expression of cytokines interleukin-8, interleukin-10, and VEGF) on the days 3, 7, 14 and 21. The obtained data were analyzed by IBM SPSS.21 software and using Kolmogorov-Smirnov, Kruskal-Wallis, and Mann-Whitney tests with p ≤ 0.05. Results: The average diameter of microvesicles was 174 ± 52nm. The thickness of the layers was 2mm. The wounds of the group post-biotic and positive control were closed on the 14th day. Collagen production and epithelialization, as well as inflammation control in the treatment groups, were higher than negative control. Conclusion: The use of chitosan membranes, particularly those enhanced with ACS and microvesicles, represents a significant advancement in wound care by inflammation control, offering a promising strategy for improving the healing of burn wounds. 408 423 2024/03/172024/07/212024/09/102024/09/52024/09/7 1403/6/17 2025/02/172025/05/72025/02/162025/04/82024/12/31 1403/10/11 Seyed Amin Mousavinezhad Seyed Amin Mousavinezhad Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Iran mousavinezhad101@gmail.com Naser Harzandi Naser Harzandi Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Iran nasharzan@gmail.com Azam Marjani Azam Marjani Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran Iran marjani.chemistry@gmail.com Parvaneh Jafari Parvaneh Jafari Department of Microbiology, Arak Branch, Islamic Azad University, Arak, Iran Iran parvaneh.jafari@gmail.com Wound healing Microvesicle Chitosan Bifidobacterium bifidum Ahn C-B, Jung W-K, Park S-J, Kim Y-T, Kim W-S, Je J-Y. 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A new accessible source of endometrial mesenchymal stem cells: a promising strategy for liver regeneration and repair in a rat model of chemotherapy-induced injury 2 2 Introduction: Alkylating agents, commonly used in chemotherapy, can cause significant liver damage by inducing cell death pathways. Human menstrual blood-derived mesenchymal stem cells (HuMenSCs), with their remarkable proliferative capacity and easy accessibility, offer a potential treatment for this injury. Methods: We investigated the impact of transplanting HuMenSCs in rats using a liver damage model caused by Busulfan injection (36 mg/kg, i.p.). Engraftment was confirmed using fluorescence microscopy and flow cytometry. Hepatic morphology was assessed via histopathological examination. Apoptosis was quantified by TUNEL assay and real-time PCR analysis of apoptotic (Bax) and anti-apoptotic (Bcl2) gene expression. Results: HuMenSCs effectively engrafted into injured liver tissue. Histopathological examination revealed hepatic morphology significantly improved in the group treated with HuMenSCs, with reduced inflammation, congestion, and sinusoidal dilation. Additionally, both the TUNEL assay and real-time PCR analysis demonstrated a significant decrease in apoptosis and a shift toward the downregulation of pro-apoptotic gene expression (Bax) in the group that received HuMenSCs treatment when compared with the sham (p < 0.0001) and negative control groups (p < 0.001). Conclusion: The results of our research suggest that HuMenSCs transplantation effectively mitigates Busulfan-induced liver injury by inhibiting apoptosis and promoting liver regeneration. These findings demonstrate the promise of HuMenSCs as a novel therapeutic approach for treating liver damage caused by chemotherapy. 424 438 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/23 1403/9/3 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/7 1404/2/17 parastoo noory parastoo noory Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran noory.parastoo@yahoo.com Hamed Hajmoradi Hamed Hajmoradi Department of Internal Medicine, School of Medicine, AJA University of Medical Sciences, Tehran, Iran Iran hamedhajmoradi@gmail.com Mehdi Abbasi Mehdi Abbasi Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran abbasima@tums.ac.ir Naghmeh Bahrami Naghmeh Bahrami Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran n-bahrami@sina.tums.ac.ir Jafar Ai Jafar Ai Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran jafar_ai@tums.ac.ir Apoptosis Endometrial mesenchymal stem cells Liver regeneration Hepatotoxicity Menstrual blood Ayatollahi M, Hesami Z, Jamshidzadeh A, Gramizadeh B. 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Long-term exposure to waterpipe tobacco smoke attenuates the positive effect of moderate exercise training on heart rate variability in male rats 2 2 Introduction: According to earlier research, fitness training can reduce the cardiovascular risks of waterpipe tobacco use. This study aimed to investigate how electrocardiogram (ECG) parameters and heart rate variability (HRV) changes occur in Wistar rats exposed to continuous hookah smoke and moderate endurance exercise training. Methods: 28 adult male Wistar rats, weighing 180–220 g, were divided into 4 groups as control group (CTL), exercise training group (Ex), waterpipe tobacco smoke exposure group (WPS), andexercise training and waterpipe tobacco smoke group (WPS+Ex). After completing the 8-week smoke exposure and exercise protocol, ECG recording, HRV characteristics, including frequency domains, temporal domains, and non-linear analysis, were computed. Results: The findings showed that, compared to the control group, hookah smoking significantly increased the RR interval (P < 0.05) and decreased heart rate (HR) and standard deviation of the second heart rate variation (SD2), an indicator of long-term HRV variability. Compared to the CTL group, exercise training decreased the low frequency/high frequency (LF/HF) band non-significantly and increased the HF band while decreasing the LF band (P<0.05). Following exposure to hookah smoking and exercise training, the WPS+Ex group’s SD2 rose (P<0.05), whereas the WPS group’s HF and corrected QT (QTc) interval decreased. Conclusion: Overall, our results demonstrated that 8 weeks of moderate-intensity endurance training had a slight favorable impact on the rats’ HRV frequency domains. At the same time, hookah smoking inhibited this beneficial effect and lowered HR. 439 449 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/232025/03/28 1404/1/8 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/72025/10/14 1404/7/22 Hossein Iranpoor Hossein Iranpoor Physiology Research Center, Institute Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran Iran aminrajizadeh2@gmail.com Samaneh-sadat Alavi Samaneh-sadat Alavi Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran, and Department of Physiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran Iran alavisamaneh@ymail.com Siyavash Joukar Siyavash Joukar Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Iran sjokar@gmail.com Mohammad Amin Rajizadeh Mohammad Amin Rajizadeh Physiology Research Center, Institute Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran Iran aminrajizadeh@yahoo.com Tobacco smoking Endurance training Heart rate variability Electrocardiogram Animal model Ahmadian M, Ghorbani S, Roshan V D, Leicht A S. 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Alpha lipoic acid and Cleome droserifolia extract as possible protective agents against mercuric chloride induced hepatorenal toxicity in male albino rats 2 2 Introduction: Mercury chloride is commonly used in our daily lives due to its diverse applications and can induce hepatorenal toxicity even at low doses. The present investigation studies the preventive effects of lipoic acid and Cleome droserifolia extract against mercury induced hepatorenal toxicity. Methods: Thirty male albino rats were randomly assigned to six experimental groups. The f irst group served as the normal control. The second group was treated with alpha-lipoic acid (ALA) at a dose of 10 mg/kg. The third group received Cleome droserifolia extract (CD) at the same dose. The fourth group was exposed to mercuric chloride (HgCl2 ) at 35 mg/kg (equivalent to 21% of the LD50 ). The fifth group was co-treated with alpha-lipoic acid (10 mg/kg) and mercuric chloride (35 mg/kg), while the sixth group received Cleome droserifolia extract (10 mg/kg) together with mercuric chloride (35 mg/kg). All treatments were administered orally once daily for a period of eight weeks. Results: Mercury induced a slight decline in body weights and relative organ weights for the liver and kidney compared to the normal control group. It caused significant elevations (p<0.05) in hamoglobin concentration and white blood cell (WBC) count; however, bone marrow cell count was not affected. Mercury triggered considerable disruption in liver and kidney functions. It also promoted a significant decline in catalase (CAT) activity and a significant elevation in malondialdehyde (MDA) levels. Mercury-induced degeneration, f ibrosis, and necrosis in the liver and kidney tissues. Administration of alpha lipoic acid and Cleome droserifolia extract showed marked improvement in the different parameters under investigation. Conclusion: Lipoic acid was found to be more effective against mercury chloride-induced hepatorenal toxicity than Cleome droserifolia extract. 450 463 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/232025/03/282024/08/6 1403/5/16 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/72025/10/142024/11/25 1403/9/5 Mohamed Shalan Mohamed Shalan Zoology and Entomology Department, Faculty of Science, Arish University, Egypt Egypt mohammed.shalaan@sci.aru.edu.eg Mercuric chloride Lipoic acid Cleome droserifolia extract Fibrosis Necrosis Abdel Moneim AE. The neuroprotective effect of berberine in mercury-induced neurotoxicity in rats. Metabolic Brain Disease 2015; 30(4): 935-942.##Abdel-Kader MS, Alqasoumi SI, Al-Taweel AM. Hepatoprotective constituents from Cleome droserifolia. 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Exploring the antidepressant-like effects of atorvastatin in ovariectomized mice: involvement of the nitric oxide pathway 2 2 Introduction: Atorvastatin, a lipid-soluble statin, is commonly used in managing high cholesterol levels and has been demonstrated to possess pleiotropic effects, such as antidepressant and neuroprotective properties. Women are more likely to suffer from depression because hormone levels change during ovariectomy and menopause. However, the role of statins in the treatment of ovariectomy-induced depressive behavior has not been adequately studied. We explored atorvastatin’s potential antidepressant effects as well as the potential function of the nitric oxide pathway in ovariectomized (OVX) mice. Methods: Female mice underwent ovary removal, followed by administration of varying doses of atorvastatin alone or in conjunction with either a non-specific NO synthase inhibitor (L-NAME) or an NO precursor (L-arginine). Behavioral alterations were assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT), while hippocampal nitrite levels were also measured. Results: One week post-procedure, OVX mice displayed a notably longer period of immobility in comparison to the sham group. OVX animals treated with atorvastatin (0.1 and 1 mg/kg) demonstrated antidepressant properties; additionally, OVX mice that received a sub effective dose of atorvastatin plus a sub-effective dose of L–NAME demonstrated pronounced antidepressant-like effects (P<0.05). L-arginine counteracted the antidepressant-like effects of a high dose of atorvastatin in OVX mice but did not affect their levels of locomotor activity in the OFT. Furthermore, atorvastatin administration prevented the increased hippocampal nitrite concentrations caused by ovariectomy (P<0.05). Conclusion: The research revealed that atorvastatin exhibits significant antidepressant properties in OVX mice, potentially by suppressing the nitric oxide pathway. 464 475 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/232025/03/282024/08/62024/07/13 1403/4/23 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/72025/10/142024/11/252024/11/23 1403/9/3 samane jahanabadi samane jahanabadi Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran sjahanabadi@yahoo.com Pegah Safshekan Pegah Safshekan Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran pegah.3373@yahoo.com Ali Moradi Ali Moradi Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran Iran morady2008@gmail.com Ovariectomy Depression Atorvastatin Nitric Oxide Mice Akyol m, Herken H, Uz E, Fadıllıoǧlu E, nal S, Sǧt S, et al. 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Exploring expression alterations in Mef2a, Tcf3, and Bdnf genes following maternal separation in the rat brain: implications for neural plasticity 2 2 Introduction: Mother-infant interaction is critical for neural development and maturation, with long-term molecular and behavioral impacts on offspring. Rats’ neonatal maternal separation (MS) has been introduced as a model of early life stress, which may be the basis of mental health condition in adulthood. In the present study, the gene expression of Mef2a, Tcf3, and Bdnf was studied in various brain regions of rat offspring that experienced MS to provide further insight into the molecular mechanism of MS. Methods: In this experimental study, MS was applied in rat litters separated from their mothers for four hours/day from PND 2 to PND 14. Mef2a, Tcf3, and Bdnf gene expression in various brain areas of adult offspring was measured by qPCR, and results were compared with the control group by t-test statistics. Results: Quantitative analyses indicated that Mef2a has been downregulated in the amygdala of offspring that experienced MS. Tcf3 gene expression was increased in the insula and striatum, while its level was decreased in the PFC of MS offspring. Bdnf was also upregulated in the insula but downregulated in the MS group’s PFC. Conclusion: Neonatal MS-induced gene expression changes the molecular drivers of neural plasticity in the offspring’s central nervous system, which may be the basis of behavioral changes in adulthood. Further investigation of signaling pathways and behavioral modifications of rats that experienced MS may uncover the underlying mechanism of MS. 476 483 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/232025/03/282024/08/62024/07/132024/08/31 1403/6/10 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/72025/10/142024/11/252024/11/232025/02/3 1403/11/15 Kimia Rahimian Kimia Rahimian Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Fariba Khodagholi Fariba Khodagholi Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Ehsan Asadi Ehsan Asadi Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Maryam Alsadat Mousavi Maryam Alsadat Mousavi Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Sareh Asadi Sareh Asadi Neurobiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran sarehasadi@gmail.com Maternal separation Mef2a Tcf3 Bdnf Brain Aboghazleh R, Boyajian S D, Atiyat A, Udwan M, Al-Helalat M, Al-Rashaideh R. 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Targeting of demyelinated lesions in experimental models of multiple sclerosis using a fibrin binding peptide 2 2 Introduction: Multiple sclerosis (MS) is an autoimmune and inflammatory disease of the central nervous system characterized by demyelination, astrogliosis, blood-brain barrier (BBB) disruption, and axonal damage. Currently available clinical and experimental approaches for MS are not completely effective because of the inability to pass the BBB, off-target distribution, and the need to increase the dosage. It has been shown that BBB disruption and fibrin deposition occur in the region of lesions in MS. Coagulation factor XIII binds to fibrin through the heptapeptide NQEQVSP in its structure. Here, NQEQVSP was used to target the lesions in animal models of MS. Methods: Microglia, astrocytes, and oligodendrocytes were immuno- stained using antibodies against Iba1, GFAP, and MBP, respectively. Results: We showed that peptide NQEQVSP binding was specific to the lesion sites induced by lysophosphatidylcholine (LPC) injection into the corpora callosa of mice. The peptide was FAM labeled, and its co-localization with different glial cells was evaluated. Co-localization was mainly detected with the microglia in the damaged area. A lower level of co-localization was also observed for oligodendrocytes. Conclusion: Our results promise the possibility of using NQEQVSP peptide to target the lesions for specific drug delivery in patients suffering from multiple sclerosis. 484 491 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/232025/03/282024/08/62024/07/132024/08/312024/03/13 1402/12/23 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/72025/10/142024/11/252024/11/232025/02/32025/01/21 1403/11/2 Sahar Farhangi Sahar Farhangi Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Iran farhangi.sahar72@gmail.com vahid sheibani vahid sheibani Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran Iran v_sheibani@kmu.ac.ir Mohammad Javan Mohammad Javan Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Iran mjavan@modares.ac.ir Targeting Peptide Fibrin Targeted delivery Glial cells Multiple sclerosis Absinta M, Lassmann H, Trapp B. 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Corrigendum to “Pancreatic HB9 protein expression is affected by long-term high-fat diet in female rat dams” [Physiol Pharmacol 29 (2025) 284-292] 2 2 Introduction: Maternal high-fat feeding has been identified as a risk factor for metabolic disorders involving abnormal glucose homeostasis and reduced whole-body insulin sensitivity. Recognizing factors like HB9, which play a role in the development of pancreatic β-cells and the release of insulin, is crucial for preventing disruptions in glucose metabolism. Methods: Twenty female Wistar rats were randomly divided into normal (N) and high-fat (HF) groups, each receiving their specific diets during the pre-pregnancy, pregnancy, and lactation periods (10 weeks). At the end of lactation, the animals’ body weight, food consumption, and calorie intake were measured. Additionally, fasting plasma levels of glucose, insulin, and corticosterone were assessed, and the homeostatic model assessment of β-cell function (HOMA-β) was calculated. Pancreatic tissue was collected to evaluate HB9 protein levels, while the adrenal glands were separated and weighed. Results: The HF group showed significant increases in adrenal gland weight, plasma corticosterone levels, and pancreatic HB9 protein expression compared to the N group. Despite this, there were no significant variations in plasma glucose and insulin concentrations, HOMA-β index, or body weight among the study groups. Whereas, the HF group consumed less food. Conclusion: Chronic intake of high-fat foods can act as a psychophysical stressor, triggering the hypothalamic-pituitary-adrenal (HPA) axis and resulting in elevated plasma corticosterone levels in female rat dams. This rise in corticosterone may lead to an upsurge in HB9 protein expression, potentially preventing disturbances in glucose regulation. 492 492 2024/03/172024/07/212024/09/102024/09/52024/09/72024/11/232025/03/282024/08/62024/07/132024/08/312024/03/132025/12/24 1404/10/3 2025/02/172025/05/72025/02/162025/04/82024/12/312025/05/72025/10/142024/11/252024/11/232025/02/32025/01/212021/07/14 1400/4/23 Roxana Karbaschi Roxana Karbaschi Faculty of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Mina Salimi Mina Salimi Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran Iran Homeira Zardooz Homeira Zardooz Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran homeira_zardooz@sbmu.ac.ir Chronic high-fat diet HB9 protein expression Pancreas ## ##