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Strategies for Stem Cell-Based Therapy for Inner Ear Cochlear Regeneration 2 2 The organ of Corti of mammals has an organized structure in which row of inner and outer hair cells (HCs) are enclosed within the numerous cells on the basilar membrane. Given the prevalence of sensorineural hearing loss due to aging and acoustic insult, it is highly desirable to develop a protocol that produces cochlear sensory cells and their associated spiral sensory neurons as a tool to advance understanding of inner ear development. The replacement of damaged auditory neurons holds promise for significantly improving clinical outcomes in deaf patients. Cell therapy is one of the treatment options for deafness. The progress in cell therapy and reprogramming techniques has opened avenues to stimulate either endogenous or transplanted stem cells, aiming to replace and repair damaged inner ear HCs and restore auditory function. In fact, current research focuses on generating functional HCs. Various approaches are being explored to regenerate auditory HCs and facilitate neural connections. Here is an overview of existing experimental culture setups for the HCs and auditory neurons regeneration and their potential treatment for hearing disorders. 331 344 2022/06/13 1401/3/23 2023/01/9 1401/10/19 ali asghar Peyvandi ali asghar Peyvandi Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Iran peyvandi@sbmu.ac.ir Hojjat-Allah Abbaszadeh Hojjat-Allah Abbaszadeh Department of Anatomical Sciences and Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Iran abbaszadeh@sbmu.ac.ir Shahrokh Khoshsirat Shahrokh Khoshsirat Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran shahrokhkhoshsirat@sbmu.ac.ir Alireza Zali Alireza Zali Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran,Iran Iran a.zali@sbmu.ac.ir somayeh niknazar somayeh niknazar 1.Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran niknazar@sbmu.ac.ir Cell therapy Hair cells Spiral ganglion neurons Regeneration Agterberg MJ, Versnel H, van Dijk LM, de Groot JC, Klis SF. Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs. JARO 2009; 10: 355-67. https://doi.org/10.1007/s10162-009-0170-2##Alsina B, Giraldez F, Varela-Nieto I. Growth factors and early development of otic neurons: Interactions between intrinsic and extrinsic signals. Curr Top Dev Biol 2003; 57: 177-206. https://doi.org/10.1016/S0070-2153(03)57006-5##Bader J, Mast-Gerlach E, Popović MK, Bajpai R, Stahl U. Relevance of microbial coculture fermentations in biotechnology. J Appl Microbiol 2010; 109: 371-87. https://doi.org/10.1111/j.1365-2672.2009.04659.x##Bakhtiarzadeh F, Nahavandi A, Goudarzi M, Shirvalilou S, Rakhshan K, Niknazar S. Axonal transport proteins and depressive like behavior, following chronic unpredictable mild stress in male rat. Physiol Behav 2018; 194: 9-14. https://doi.org/10.1016/j.physbeh.2018.04.029##Baumgartner LS, Moore E, Shook D, Messina S, Day MC, Green J, et al. Safety of autologous umbilical cord blood therapy for acquired sensorineural hearing loss in children. 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Science 2000; 288: 1660-3. https://doi.org/10.1126/science.288.5471.1660##Coleman B, Fallon J, Pettingill L, De Silva M, Shepherd R. Auditory hair cell explant co-cultures promote the differentiation of stem cells into bipolar neurons. Exp Cell Res 2007; 313: 232-43. https://doi.org/10.1016/j.yexcr.2006.10.010##Coleman B, Hardman J, Coco A, Epp S, De Silva M, Crook J, et al. Fate of embryonic stem cells transplanted into the deafened mammalian cochlea. Cell Transplant 2006; 15: 369-80. https://doi.org/10.3727/000000006783981819##Ding D-C, Shyu W-C, Lin S-Z. Mesenchymal stem cells. Cell Transplant 2011; 20: 5-14. https://doi.org/10.3727/096368910X##Dufner-Almeida LG, Cruz DBd, Mingroni RC, Batissoco AC, Oiticica J, Salazar-Silva R. Stem-cell therapy for hearing loss: Are we there yet? Braz J Otorhinolaryngol 2019; 85: 520-9. https://doi.org/10.1016/j.bjorl.2019.04.006##Fransson A, Maruyama J, Miller JM, Ulfendahl M. 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The therapeutic effects of erythropoietin and carbamylated erythropoietin derivatives in neurological and other disorders 2 2 Erythropoietin (EPO) has been considered in several studies as a significant factor in the development of erythroid cells, the inhibition of neuronal cell death, and neurogenesis. Fortunately, a modified version of EPO called carbamylated erythropoietin (CEPO) possesses tissue-protective properties without eliciting erythropoietic effects. CEPO is a derivative of EPO that results in an alpha-amino derivative group with less biological hematopoiesis than EPO. In neurological diseases, CEPO and its carbamylated erythropoietin Fc fusion protein (CEPO-Fc) has been shown to play a better role than EPO. In this study, the effects of EPO and its derivatives on neurological diseases and their role in treatment have been reviewed. 345 356 2022/06/132022/08/25 1401/6/3 2023/01/92023/02/20 1401/12/1 Amirhossein Maghsoudi Amirhossein Maghsoudi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran amirhosein.maghsoudi@yahoo.com Jalal Zaringhalam Jalal Zaringhalam Faculty member of Physiology Department, School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran Iran jzaringhalam@gmail.com Maryam Moosavi Maryam Moosavi Nanomedicine and Nanobiology Research Centre, Shiraz University of Medical sciences, Shiraz, Iran Iran mmoosavi2000@gmail.com Akram Eidi Akram Eidi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran eidi@srbiau.ac.ir EPO CEPO Neurological disorders Alzheimer’s disease Adembri C, Massagrande A, Tani A, Miranda M, Margheri M, De Gaudio R, et al. 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Herbal treatment options for female fertility disorders: a systematic review of clinical trials 2 2 Introduction: Herbal medicine has been used as tea, ointment, capsules, syrup, whole herbs, and tablets to treat fertility disorders. The herbs and their treatment use in different localities vary, and the effectiveness of herbal treatment for routine treatment of diseases is still a debated issue to date. This study is a 20-year review of the herbal medicines treatment options for female fertility disorders to provide an updated publication of herbal treatments for female infertility and their associated outcomes, informing further research or translation. Methods: PubMed, Google Scholar, Web of Science, Science Direct, and Cochrane databases were searched for clinical trials using Medical Subject Headings (MeSH) terms and related keywords, which retrieved 336 studies. All cross-sectional studies, reviews, and controlled trials utilizing phytotherapy on study participants without evidence of female infertility were excluded. Only 23 studies published in the English Language between January 2002 and August 2021 were included in the evidence synthesis after article screening. Results: Several herbal treatments in women cause a significant reduction in the symptoms of primary dysmenorrhea, PCOS, endometriosis, luteal phase defect, and vulvovaginal candidiasis, with substantial improvements in pregnancy and live birth rates. The herbal drugs identified from available studies were formulations – tablets or creams - with specified doses and administered orally or intravaginally. Conclusion: Evidence exists that herbal treatments effectively treat female fertility disorders. However, they have not fully established the extent of safety, side effects, and pharmacological mechanisms of the therapeutic effects attributed to these herbal treatments. 357 386 2022/06/132022/08/252022/02/23 1400/12/4 2023/01/92023/02/202022/12/17 1401/9/26 Izuchukwu Azuka Okafor Izuchukwu Azuka Okafor Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, PMB 5001, Nnewi, Nigeria Nigeria iza.okafor@unizik.edu.ng Ndubuisi Paris Obi Ndubuisi Paris Obi Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, PMB 5001, Nnewi, Nigeria Nigeria parisflashy@gmail.com Kingsley Chinemerem Ibeabuchi Kingsley Chinemerem Ibeabuchi College of Nursing Sciences, Our Lady of Lourdes Hospital Complex, Ihiala, Anambra State, Nigeria Nigeria kingsleychinemerem@gmail.com Herbal therapy Infertility treatment Natural remedy Alternative medicine Update review Abu-Rabia A. 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Assessment of defects in peripheral and central transmission of auditory Assessment of Defects in Peripheral and Central Transmission of Auditory Pathway Using Brainstem Auditory Evoked Potentials in Preterm Babies pathway by Brainstem Audiometry Evoked Potentials in preterm babies 2 2 Introduction: Brainstem Auditory Evoked Potentials (BAEP) play a crucial role in pediatric audiology, particularly for evaluating auditory function in children when behavioral testing is not possible. It serves as a valuable tool for assessing the auditory pathways of the brainstem. Methods: This study aims to compare latencies of wave I and wave III through Brainstem Auditory Evoked Potential (BAEP) in preterm babies (32 to 36 weeks) against age specific normal responses. The goal is to identify potential hearing impairment indicated by any increased BAEP latencies in wave I and wave III. Results: The study involved 50 preterm newborns divided into three groups based on gestational age: Group A (32 weeks, n=12), Group B (34 weeks, n=18), and Group C (36 weeks, n=20). The infants underwent BAEP testing using the RMS EMG EP MARK-II machine at the Neurophysiology Unit of the Department of Physiology, Gandhi Medical College, Bhopal. Data interpretation involved comparing the obtained values to established normal values. Conclusion: The study observed increased absolute peak latencies of wave I and III in preterm babies compared to normal term infants, suggesting defects in peripheral transmission and improper myelination of the BAEP pathway. When comparing between groups, significant differences were found in the absolute latencies of waves I and III in both ears between group 1 and groups 2 and 3. Additionally, significant differences were noted in the latency of waves I and III in the right ear between group 2 and group 3. 387 391 2022/06/132022/08/252022/02/232022/07/23 1401/5/1 2023/01/92023/02/202022/12/172023/01/21 1401/11/1 Brajesh Sharma Brajesh Sharma MPMSU JABALPUR, India India drsharma.brajesh@gmail.com Sanjeev Kumar Shrivastava Sanjeev Kumar Shrivastava mpmsu jabalpur, India India sanjeevshrivastava8@gmail.com Nandini Shukla Nandini Shukla MPMSU Jabalpur, India India knsnandini1986@gmail.com Rashmi Dave Rashmi Dave MPMSU JABALPUR MADHYA PRADESH, India India rdave1987@gmail.com Asha Shrivastava Asha Shrivastava MPMSU Jabalpur, India Iran drashashrivastava@gmail.com Brainstem Auditory Evoked Potential Peripheral transmission Improper myelination Agrawal VK, Shukla R, et al. Brainstem auditory evoked response in newborns with hyperbilirubinemia. Indian Pediat 1998; 35: 513-18.##Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard score, expanded to include extremely premature infants. J Pediatr 1991; 119: 417-423.##Bilgen H, Akman I, Ozek E, Kulekel S, Rahmi ORS, Carman F Auditory brainstem response screening for hearing loss in high risk neonates. Turk J Med Sci 2000; 30: 479-82.##Despland PA. Maturational changes in the auditory system as reflected in human brainstem evoked responses. Dev Neurosci 1985; 7: 73-80.##Dobbing J, Sands J. Quantitative growth and development of human brain. Arch Dis Child 1973; 48: 757-67.##Eggermont JJ, Salamy A. Maturational time course for the ABR in preterm and full term Infants Hear Res 1988; 33: 35-48.##Engle WA, Tomashek KM, Wallman C. “Late-preterm” infants: a population at risk. J Pediatr 2007; 120(6): 1390-401.##Goldstein PJ, Krumholz A, Felix JK, Shannon D, Carr RF. Brainstem evoked response in neonates. AJOG 1979; 135: 622-8.##Jiang ZD, Wilkinsons AR. Normal brainstem responses in moderately preterm infants. Acta Pediatr 2008; 97(10): 1366-9.##Joint Committee on Infant Hearing. American Academy of Pediatrics. American Speech - Language - Hearing Association. Directors of speech and hearing programs in State Health and Welfare Agencies. Year 2007 Position statement: Principles and Guidelines for early hearing detection and intervention programs. Pediatrics. 2007; 120 (4) 898 - 921.##Kilic I, Karahan H, Kurt T, Ergin H, Sahiner T. Brainstem evoked response audiometry and risk factors in premature infants. Marmara Med J 2007; 20(1):21-8.##Maisels JM, Avery GB, Fletcher MA, MacDonald MG. Neonatology, pathophysiology and management of the newborn. Philadelphia JB Lippincott Co 1994. 630-725.##Norman MG. Perinatal brain damage. Per sped Pediatric Pathol 1975; 4: 41-92.##Pasman JW, Retteveel JF, de Graaf R, Maassen B, Visco YM. The effects of early and late preterm birth on brainstem and middle-latency auditory evoked responses in children with normal neurodevelopment. 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Neuroprotective effect of Acorus calamus Linn. extract on a rat model of chronic constriction injury of median nerve-induced peripheral neuropathy 2 2 Introduction: Acorus calamus Linn. from the Acoraceae family exhibits several benefits in neurological disorders but has not been studied for chronic constriction injury (CCI) of median nerve induced neuropathic pain. Damage to median nerve leads to work-related musculoskeletal disorders (WMSDs). this study aimed to assess the effects of the ethanolic root extract of Acorus calamus (EAC) on CCI-induced neuropathic pain and WMSDs in rats. Methods: Animals were randomly divided into 7 groups of 8 animals each. Group 1. Normal control, 2. Sham control, 3. CCI, 4. CCI+ vehicle (CMC), 5. CCI+gabapentin (50 mg/kg), 6. CCI+EAC (20 mg/kg), 7. CCI+EAC (40 mg/kg). On day 0, rats were subjected to the surgical procedure of exposure and ligation of the median nerve-produced CCI at the forearm level. Pain-sensitive tests (i.e., hot plate test, Randall Selitto test), and functional analysis (i.e., walking track) were performed. Total protein, lipid peroxidation, and histopathological changes were also estimated. Results: CCI significantly increased thermal and mechanical hyperalgesia, raised median functional index (walking track analysis), and induced biochemical and histological disruptions. Oral administration of EAC (40 mg/kg) and gabapentin (50 mg/kg) notably lowered CCI-induced nociceptive pain threshold, improved median nerve functional index, and mitigated tissue histological alterations. Conclusion: EAC has been found to decrease CCI-induced neuropathic pain of the median nerve. Its mechanisms likely involve neuroprotective, antioxidant, and anti-inflammatory properties. 392 402 2022/06/132022/08/252022/02/232022/07/232022/07/9 1401/4/18 2023/01/92023/02/202022/12/172023/01/212022/12/31 1401/10/10 Shubhechha Bansod Shubhechha Bansod Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune India bansod.s1998@gmail.com Likhit Akotkar Likhit Akotkar Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune, India India likhitakotkar254@gmail.com Subhash Bodhankar Subhash Bodhankar Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune, India India sbodh@yahoo.com Urmila Aswar Urmila Aswar Associate Professor, Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune, India India aswarurmila@gmail.com Acorus calamus Median nerve injury Nerve functional index Neuroprotection Neuropathic pain Walking track analysis Anwer S, Li H, Antwi-Afari MF, Wong A. 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Safranal Ameliorates Ischemic/Reperfusion Injury Induced by Testicular Torsion in Rat 2 2 Introduction: Testicular torsion is very common in urological emergencies, which damages testicular tissue and reproductive function. Safranal, known for its robust antioxidant properties, has demonstrated effective inhibition of ischemia/reperfusion injury (IRI) in various tissues such as the hippocampus, cerebral, and skeletal muscles. Therefore, this study aimed to evaluate the effect of Safranal on testicular tissue following IRI. Methods: This research involved 48 male adult Wistar rats. They were randomly divided into six groups: control, testicular torsion/detorsion (TD), torsion and detorsion/safranal (0.1, 0.5 mg/kg, ip), and safranal control groups (0.1, 0.5 mg/kg, ip). Under anesthesia, the left testicular torsion was induced for four hours, 30 minutes before detorsion, a single dose of safranal was injected. After 24 hours of reperfusion, assessments encompassing oxidative markers, estradiol, testosterone, LH hormone, sperm parameters, testicular histopathology, and gene expression were conducted on blood and tissue samples. Results: Heightened seminiferous epithelia (HE) was observed in the TD groups receiving safranal (TD+Sa 0.1, 0.5). There was a significant increase in sperm count and a notable reduction in abnormal sperm count compared to the TD group. Also, the expression of the Bax gene significantly decreased in comparison to the TD group. In rats receiving 0.1 mg/ kg of safranal, there was an improvement in superoxide dismutase (SOD) and glutathione peroxidase (GPx). Although not statistically significant, the TD+Sa groups exhibited slightly enhanced levels of estradiol, testosterone, and LH compared to the TD group. Conclusion: These findings suggest that safranal may protect testicular tissue from IRI through antioxidant and antiapoptotic pathways. 403 416 2022/06/132022/08/252022/02/232022/07/232022/07/92022/06/26 1401/4/5 2023/01/92023/02/202022/12/172023/01/212022/12/312023/01/11 1401/10/21 Marzieh Ebrahimi Marzieh Ebrahimi Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran Iran Marzieh.ebr74@gmail.com Seyed-Hosein Abtahi-Evari Seyed-Hosein Abtahi-Evari Department of Biochemistry, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Iran Abtahi.h@gmu.ac.ir Balal Brazvan Balal Brazvan Department of anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Iran bbarazvan@gmail.com Majid Shokoohi Majid Shokoohi Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Iran a.shokoohy@yahoo.com Malihe Soltani Malihe Soltani Department of anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Iran soltanimalihe@yahoo.com Morteza Rostamian Morteza Rostamian English department, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Iran m.rostamian.edu@gmail.com Masoumeh Fani Masoumeh Fani Department of anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Iran m.fani2017@yahoo.com Maryam Moghimian Maryam Moghimian Department of Physiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Iran moghimin.m@gmu.ac.ir Torsion-Detorsion Safranal Oxidative Markers Bax/Bcl-2 Apoptosis Abdullaev FI. 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Diverse long-term exercise intensity effects on appetite and body weight regulation: Arcuate Neuropeptide -Y and Proopiomelanocortin gene function 2 2 Introduction: The effectiveness of various extrinsic and intrinsic regulatory signals on food intake and body weight can be influenced by hypothalamic neuropeptide-Y (NPY) and proopiomelanocortin (POMC) neurons. While several studies emphasize the vital role of regular physical activity in effective weight management, how these molecular and cellular processes interact with physical activity remains an area in need of further exploration. Hence, this study aims to investigate the impact of various long-term physical activities intensities on the regulation of body weight and appetite. Methods: Twenty-one Wistar rats (n=7) were randomized into three groups: 1) Control group, 2) a group engaged in regular exercise at moderate intensity for 24 weeks (24-ME, 5 days each week), and 3) a group frequently and intensively exercising over 24 weeks (24-IE, 5 days each week). Subsequently, Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods were performed to measure gene expression of hypothalamic arcuate nucleus NPY and POMC, as well as serum levels of acyl-ghrelin and leptin. Results: The POMC mRNA level decreased in the 24-ME group compared to the control rats. However, intensive regular exercise increased NPY expression compared to the control rats. Inversely, body weight and food intake levels were considerably higher in the 24-ME and 24-IE groups than in the control group. Different intensities of prolonged exercise seem to heighten appetite, eventually increasing body weight through distinct molecular pathways. Conclusion: Hence, it can be concluded that prolonged intensive exercise may not be a practical approach for weight loss. 417 425 2022/06/132022/08/252022/02/232022/07/232022/07/92022/06/262022/05/16 1401/2/26 2023/01/92023/02/202022/12/172023/01/212022/12/312023/01/112023/01/9 1401/10/19 Nazli Khajehnasiri Nazli Khajehnasiri Assistant Professor in Animal Physiology, Higher Education Institute of Rab-Rashid, Tabriz, Iran Iran nkhajehnasiri94@gmail.com mostafa hosseini mostafa hosseini Department of Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran Iran hosseinimostafa2112@sbu.ac.ir Parivash Piraki Parivash Piraki Dareh Shahr Branch, Islamic Azad University, Dareh Shahr, Iran Iran Piraki94@sbu.ac.ir Mahnaz Ghowsi Mahnaz Ghowsi Department of biology, Faculty of Sciences, Razi University, Kermanshah, Iran Iran ghowsi.mahnaz@sbu.ac.ir Leila Rahbarnia Leila Rahbarnia Tabriz University of Medical Sciences, Tabriz, Iran Iran lerahbarnia@sbu.ac.ir Parisa Habibi Parisa Habibi Assistant Professor of Physiology, Hamadan University of Medical Sciences, Hamadan, Iran Iran Parisa.Habibi@umsha.ac.ir Reihaneh Sadeghian Reihaneh Sadeghian Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran Iran re.sadeghian1414@gmail.com Neuropeptide-Y Pro-opiomelanocortin Long-term exercise Bodyweight Appetite Ali MA, Kravitz AV. Challenges in quantifying food intake in rodents. Brain Res 2018; 1693: 188-91. https://doi.org/10.1016/j.brainres.2018.02.040##Aronne LJ, Nelinson DS, Lillo JL. Obesity as a disease state: a new paradigm for diagnosis and treatment. Clin Cornerstone 2009a; 9: 9-25; discussion 26-9. https://doi.org/10.1016/S1098-3597(09)80002-1##Aronne LJ, Nelinson DS, Lillo JL. Obesity as a disease state: a new paradigm for diagnosis and treatment. Clinical cornerstone 2009b; 9: 9-29. https://doi.org/10.1016/S1098-3597(09)80002-1##Benite-Ribeiro SA, Putt DA, Santos JM. The effect of physical exercise on orexigenic and anorexigenic peptides and its role on long-term feeding control. Med Hypotheses 2016; 93: 30-3. https://doi.org/10.1016/j.mehy.2016.05.005##Bilski J, Mańko G, Brzozowski T, Pokorski J, Nitecki J, Nitecka E, et al. Effects of exercise of different intensity on gut peptides, energy intake and appetite in young males. Ann Agric Environ Med 2013; 20.##Bilski J, Teległów A, Zahradnik-Bilska J, Dembiński A, Warzecha Z. Effects of exercise on appetite and food intake regulation. Medicina Sportiva 2009; 13: 82-94. https://doi.org/10.2478/v10036-009-0014-5##Blundell JE, Stubbs R, Hughes D, Whybrow S, King N. Cross talk between physical activity and appetite control: does physical activity stimulate appetite? Proceedings of the Nutrition Society 2003; 62: 651-61. https://doi.org/10.1079/PNS2003286##Casanova N, Finlayson G, Blundell JE, Hopkins M. Biopsychology of human appetite-understanding the excitatory and inhibitory mechanisms of homeostatic control. Curr Opin Physiol 2019; 12: 33-38. https://doi.org/10.1016/j.cophys.2019.06.007##Chen S, Chen H, Zhou J J, Pradhan G, Sun Y, Pan H, et al. Ghrelin receptors mediate ghrelin-induced excitation of agouti-related protein/neuropeptide Y but not pro-opiomelanocortin neurons. J Neurochem 2017; 142: 512-20. https://doi.org/10.1111/jnc.14080##De Bond JA, Smith JT. Kisspeptin and energy balance in reproduction. Reproduction 2014; 147: R53-63. https://doi.org/10.1530/REP-13-0509##Douglas JA, King JA, McFarlane E, Baker L, Bradley C, Crouch N, et al. Appetite, appetite hormone and energy intake responses to two consecutive days of aerobic exercise in healthy young men. Appetite 2015; 92: 57-65. https://doi.org/10.1016/j.appet.2015.05.006##Ezzati M, Lopez AD, Rodgers AA, Murray CJL. Comparative quantification of health risks : global and regional burden of disease attributable to selected major risk factors. World Health Organization 2004.##Farhadipour M, Depoortere I. The function of gastrointestinal hormones in obesity-implications for the regulation of energy intake. Nutrients 2021; 13. https://doi.org/10.3390/nu13061839##Guelfi KJ, Donges CE, Duffield R. Beneficial effects of 12 weeks of aerobic compared with resistance exercise training on perceived appetite in previously sedentary overweight and obese men. Metabolism 2013; 62: 235-43. https://doi.org/10.1016/j.metabol.2012.08.002##Hagobian TA, Sharoff CG, Stephens BR, Wade GN, Silva JE, Chipkin SR, et al. Effects of exercise on energy-regulating hormones and appetite in men and women. Am J Physiol Regul Integr Comp Physiol 2009; 296: R233-42. https://doi.org/10.1152/ajpregu.90671.2008##Han D, Kim S, Cho B. mRNA expression on neuropeptide Y (NPY) to exercise intensity and recovery time. J Phys The Sci 2011; 23: 781-4. https://doi.org/10.1589/jpts.23.781##Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282: 1568-75. https://doi.org/10.1001/jama.282.16.1568##Hill JW, Elmquist JK, Elias CF. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab 2008; 294: E827-32. https://doi.org/10.1152/ajpendo.00670.2007##Holliday A, Blannin A. Appetite, food intake and gut hormone responses to intense aerobic exercise of different duration. J Endocrinol 2017; 235: 193-205. https://doi.org/10.1530/JOE-16-0570##Jiaxu C, Weiyi Y. Influence of acute and chronic treadmill exercise on rat brain POMC gene expression. Med Sci Sports Exerc 2000; 32: 954-7. https://doi.org/10.1097/00005768-200005000-00012##Khajehnasiri N, Dehkordi MB, Amini-Khoei H, Mohammadabadi MSM, Sadeghian R. Effect of exercise intensity and duration on the levels of stress hormones and hypothalamic-pituitary-gonadal axis in adult male rats: an experimental study. Hormones (Athens) 2021; 20: 483-90. https://doi.org/10.1007/s42000-021-00303-4##Khajehnasiri N, Khazali H, Sheikhzadeh F. Various responses of male pituitary-gonadal axis to different intensities of long-term exercise: Role of expression of KNDYrelated genes. J Biosci 2018; 43: 569-574. https://doi.org/10.1007/s12038-018-9782-1##Khajehnasiri N, Khazali H, Sheikhzadeh F, Ghowsi M. One-month of high-intensity exercise did not change the food intake and the hypothalamic arcuate nucleus proopiomelanocortin and neuropeptide Y expression levels in male Wistar rats. Endocr Regul 2019; 53: 8-13. https://doi.org/10.2478/enr-2019-0002##Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 2007; 8: 21-34. https://doi.org/10.1111/j.1467-789X.2006.00270.x##Laing BT, Do K, Matsubara T, Wert DW, Avery MJ, Langdon EM, et al. Voluntary exercise improves hypothalamic and metabolic function in obese mice. J Endocrinol 2016; 229: 109-22. https://doi.org/10.1530/JOE-15-0510##Lauterio TJ, Davies MJ, DeAngelo M, Peyser M, Lee J. Neuropeptide Y expression and endogenous leptin concentrations in a dietary model of obesity. Obes Res 1999; 7: 498-505. https://doi.org/10.1002/j.1550-8528.1999.tb00439.x##Owyang C, Heldsinger A. Vagal control of satiety and hormonal regulation of appetite. J Neurogastroenterol Motil 2011; 17: 338-48. https://doi.org/10.5056/jnm.2011.17.4.338##Pomerleau M, Imbeault P, Parker T, Doucet E. Effects of exercise intensity on food intake and appetite in women. Am J Clin Nutr 2004; 80: 1230-6. https://doi.org/10.1093/ajcn/80.5.1230##Sadeghian R, Shahidi S, Komaki A, Habibi P, Ahmadiasl N, Yousefi H, et al. Synergism effect of swimming exercise and genistein on the inflammation, oxidative stress, and VEGF expression in the retina of diabetic-ovariectomized rats. Life Sci 2021; 284: 119931. https://doi.org/10.1016/j.lfs.2021.119931##Salehi M S, Namavar MR, Shirazi MRJ, Rahmanifar F, Tamadon A. A simple method for isolation of the anteroventral periventricular and arcuate nuclei of the rat hypothalamus. Anatomy 2012; 7. https://doi.org/10.2399/ana.11.212##Sartin JL, Daniel JA, Whitlock BK, Wilborn RR. Selected hormonal and neurotransmitter mechanisms regulating feed intake in sheep. Animal 2010; 4: 1781-9. https://doi.org/10.1017/S1751731110001497##Sohn JW. Network of hypothalamic neurons that control appetite. BMB Rep 2015; 48: 229-33. https://doi.org/10.5483/BMBRep.2015.48.4.272##Stubbs R, Sepp A, Hughes D, Johnstone A, King N, Horgan G, et al. The effect of graded levels of exercise on energy intake and balance in free-living women. Int J Obes 2002; 26: 866-9. https://doi.org/10.1038/sj.ijo.0801874##Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Rep 2012; 13: 1079-86. https://doi.org/10.1038/embor.2012.174##Wardlaw SL. Clinical review 127: Obesity as a neuroendocrine disease: lessons to be learned from proopiomelanocortin and melanocortin receptor mutations in mice and men. J Clin Endocrinol Metab 2001; 86: 1442-6. https://doi.org/10.1210/jcem.86.4.7388## ##

Investigating the effects of Lactobacillus acidophilus and Lactobacillus paracasei supernatant on cervical cancer cells 2 2 Introduction: Lactic acid bacteria, recognized as probiotics, have garnered significant attention as potential adjuvants in chemotherapy for various cancer types, including cervical cancer. In this study, we investigated the anti-cancer properties of two indigenous Iranian strains, Lactobacillus acidophilus and Lactobacillus paracasei, individually and in combination, targeting human cervical cancer cell lines compared to normal control cells. Methods: The cytotoxic effect of Lactobacillus acidophilus and Lactobacillus paracasei supernatants, as well as their 1:1 mixture, on CaSki and HNCF PI 52 cell lines, was evaluated using the MTT assay. The apoptotic and anti-metastatic effects of these supernatants were assessed by analyzing the gene expression of BAX/BCL2 ratio, Caspase-3, and MMP2/ MMP9 using Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Results: Significant cytotoxicity was observed in Ca Ski cells attributed to the low pH of the supernatants. The increase in the BAX/BCL2 ratio, leading to an up-regulation of Caspase-3, indicated the induction of apoptosis (P<0.001). In addition, the expression of MMP9 significantly deceased in Ca Ski cells treated with Lactobacillus acidophilus (P<0.001) and Lactobacillus paracasei (P<0.05), while no significant difference in MMP2 expression was observed in all samples compared to the control groups. Conclusion: while further validation is needed, the heightened expression of apoptotic genes suggests a potential induction of apoptosis in cancer cells in response to Lactobacillus toxicity. The significant down-regulation of the MMP9 gene emphasizes the need for comparative analyses across different cervical cancer cell lines to establish the anti-metastatic potential of these local probiotic supernatants. 426 434 2022/06/132022/08/252022/02/232022/07/232022/07/92022/06/262022/05/162022/01/31 1400/11/11 2023/01/92023/02/202022/12/172023/01/212022/12/312023/01/112023/01/92023/02/20 1401/12/1 Iman Samiei Mosleh Iman Samiei Mosleh Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran imansamiemosleh@gmail.com Fatemeh Karami Fatemeh Karami Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran Fatemeh.karami@srbiau.ac.ir Iman Salahshourifar Iman Salahshourifar Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran isalahshouri@gmail.com Maryam Tajabadi Ebrahimi Maryam Tajabadi Ebrahimi Department of Biology Central Tehran Branch Islamic Azad University Tehran Iran Iran ebrahimi_mt@yahoo.com Mohsen Marvibaigi Mohsen Marvibaigi 4 Department Biology, Kavian Institute of higher education, Mashhad, Iran Iran Cervical cancer Lactobacillus acidophilus Lactobacillus paracasei Probiotics Aminaei M, Karami F, Marvibaigi M, Sotoodehnejadnematalahi F, Tajabadi Ebrahimi M. Primary evidence on the potential of Lactobacillus paracasei in treatment of hepatocellular carcinoma. Food and Health 2018; 3: 27-9.##Badgeley A, Anwar H, Modi K, Murphy P, Lakshmikuttyamma A. Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives. Biochim Biophys Acta Rev Cancer 2021; 1875: 188494. https://doi.org/10.1016/j.bbcan.2020.188494##Chao X, Song X, Wu H, You Y, Wu M, Li L. Selection of treatment regimens for recurrent cervical cancer. Front Oncol 2021; 11: 618485. https://doi.org/10.3389/fonc.2021.618485##Chee WJY, Chew SY, Than LTL. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact 2020; 19: 203. https://doi.org/10.1186/s12934-020-01464-4##Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer. Carcinogenesis 2005; 26: 263-70. https://doi.org/10.1093/carcin/bgh283##Górska A, Przystupski D, Niemczura M J, Kulbacka J. Probiotic bacteria: A promising tool in cancer prevention and therapy. Curr Microbiol 2019; 76: 939-949. https://doi.org/10.1007/s00284-019-01679-8##Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med 2011; 17: 860-6. https://doi.org/10.1038/nm.2385##Isazadeh A, Hajazimian S, Shadman B, Safaei S, Babazadeh Bedoustani A, Chavoshi R, et al. Anti-cancer effects of probiotic lactobacillus acidophilus for colorectal cancer cell line Caco-2 through apoptosis induction. Pharm Sci 2021; 27: 262-7. https://doi.org/10.34172/PS.2020.52##Kim SN, Lee WM, Park KS, Kim JB, Han DJ, Bae J. The effect of Lactobacillus casei extract on cervical cancer cell lines. Contemp Oncol (Pozn) 2015; 19: 306-12. https://doi.org/10.5114/wo.2014.45292##Li X, Wang H, Du X, Yu W, Jiang J, Geng Y, et al. Lactobacilli inhibit cervical cancer cell migration in vitro and reduce tumor burden in vivo through upregulation of E-cadherin. Oncol Rep 2017; 38: 1561-8. https://doi.org/10.3892/or.2017.5791##Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 2017; 9. https://doi.org/10.3390/nu9091021##Mirzayi C, Renson A, Zohra F, Elsafoury S, Geistlinger L, Kasselman LJ, et al. Reporting guidelines for human microbiome research: the STORMS checklist. Nat Med 2021; 27: 1885-92. https://doi.org/10.1038/s41591-021-01552-x##Motevaseli E, Azam R, Akrami SM, Mazlomy M, Saffari M, Modarressi M H, et al. The effect of lactobacillus crispatus and lactobacillus rhamnosus culture supernatants on expression of autophagy genes and HPV E6 and E7 oncogenes in the HeLa cell line. Cell J 2016; 17: 601-7.##Motevaseli E, Shirzad M, Akrami SM, Mousavi AS, Mirsalehian A, Modarressi M H. Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate. J Med Microbiol 2013; 62: 1065-72. https://doi.org/10.1099/jmm.0.057521-0##Nouri Z, Karami F, Neyazi N, Modarressi MH, Karimi R, Khorramizadeh MR, et al. Dual anti-metastatic and anti-proliferative activity assessment of two probiotics on HeLa and HT-29 cell lines. Cell J 2016; 18: 127-34.##Riaz Rajoka MS, Zhao H, Lu Y, Lian Z, Li N, Hussain N, et al. Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct 2018; 9: 2705-15. https://doi.org/10.1039/C8FO00547H##Ryoo HD, Bergmann A. The role of apoptosis-induced proliferation for regeneration and cancer. Cold Spring Harb Perspect Biol 2012; 4: a008797. https://doi.org/10.1101/cshperspect.a008797##Sadeghi-Aliabadi H, Mohammadi F, Fazeli H, Mirlohi M. Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain. Iran J Basic Med Sci 2014; 17: 815-9.##Schröpfer A, Kammerer U, Kapp M, Dietl J, Feix S, Anacker J. Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines. BMC Cancer 2010; 10: 553. https://doi.org/10.1186/1471-2407-10-553##Sharma V, Kaur R, Bhatnagar A, Kaur J. Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling. Cell Stress Chaperones 2015; 20: 431-40. https://doi.org/10.1007/s12192-014-0568-6##Sung H, Ferlay J, Siegel R L, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-49. https://doi.org/10.3322/caac.21660##Tsakmaklis A, Vehreschild M, Farowski F, Trommer M, Kohler C, Herter J, et al. Changes in the cervical microbiota of cervical cancer patients after primary radio-chemotherapy. Int J Gynecol Cancer 2020; 30: 1326-30. https://doi.org/10.1136/ijgc-2019-000801##Wang KD, Xu DJ, Wang BY, Yan DH, Lv Z, Su JR. Inhibitory effect of vaginal lactobacillus supernatants on cervical cancer cells. Probiotics Antimicrob Proteins 2018; 10: 236-42. https://doi.org/10.1007/s12602-017-9339-x##Wen H, Guo Q-H, Zhou X-L, Wu X-H, Li J. Genomic profiling of chinese cervical cancer patients reveals prevalence of DNA damage repair gene alterations and related hypoxia feature. Front Oncol 2022; 11: 792003. https://doi.org/10.3389/fonc.2021.792003## ##

Wound Healing Effects of Frankincense and Myrrha on Adult Human Dermal Fibroblasts (HDFa) 2 2 Introduction: Oleogum resins extracted from Boswellia sacra (Frankincense) and Commiphora myrrha (Myrrha) have been traditionally used to facilitate wound healing and address skin injuries. Moreover, they have anti-inflammatory, antioxidant, and antimicrobial effects. Therefore, we hypothesized that their combination can be effective in wound healing. In this study, we evaluated the effects of methanol extracts from two oleogum resins, Boswellia sacra (Frankincense) and Commiphora myrrha (Myrrha), as well as their combination on cell migration promotion and wound healing in human dermal fibroblast cells (HDFa). Methods: The methanol extracts of B. sacra (BS) and C. myrrha (CM) and their combination were tested to determine their optimum cytoprotective concentrations using the AlamarBlue assay. The level of reactive oxygen species (ROS) was also evaluated using a DCFDA detector. To assess cell migration promotion and wound healing properties of the extracts, a scratch wound closure assay was performed in HDFa cells and the images were analyzed using ImageJ software. Western blot analysis was employed to detect the activation of fibroblast migration associated protein extracellular signal-regulated kinase (ERK). Results: Using the viability assay, the optimum non-cytotoxic concentrations of the extracts (10 and 20 µg/ml) were chosen to evaluate their wound healing effects on HDFa cells. BS, CM and BC at 10 and 20 µg/ml significantly reduced H2 O2 -induced ROS levels compared to the control. In the scratch assay, BS and BC, both at 10 µg/ml, could significantly reduce the average wound width compared to the control. Western blot analysis showed that CM significantly increased the pERK/ERK ratio compared to the control. Conclusion: These findings suggest the beneficial effects of both frankincense and myrrh, as well as their combination, in improving proliferation, migration, and thecwound healing process in HDFa. 435 444 2022/06/132022/08/252022/02/232022/07/232022/07/92022/06/262022/05/162022/01/312022/02/13 1400/11/24 2023/01/92023/02/202022/12/172023/01/212022/12/312023/01/112023/01/92023/02/202023/01/1 1401/10/11 Atefeh Kavousi Atefeh Kavousi Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical, Mashhad, Iran Iran Ati.kvc92@gmail.com Elham Nikkhah Elham Nikkhah Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Iran NikkhahE1@mums.ac.ir Zahra Tayarani-Najaran Zahra Tayarani-Najaran Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences Iran Tayaraninz@mums.ac.ir Behjat Javadi Behjat Javadi Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical, Mashhad, Iran Iran javadib@mums.ac.ir Frankincense Myrrh Wound Healing Persian Medicine Western blotting Almeida-da-Silva CLC, Sivakumar N, Asadi H, et al. Effects of Frankincense Compounds on Infection, Inflammation, and Oral Health. Molecules 2022; 27: 4174. https://doi.org/10.3390/molecules27134174##Alvarez-Suarez JM, Giampieri F, Cordero M, et al. Activation of AMPK/Nrf2 signalling by Manuka honey protects human dermal fibroblasts against oxidative damage by improving antioxidant response and mitochondrial function promoting wound healing. J Funct Foods 2016; 25: 38-49. https://doi.org/10.1016/j.jff.2016.05.008##Basil D, Kadhim H, Jasim G and Latif Q. Antibacterial activity of commiphora molmol extracts on some bacterial species in iraq. SAJP 2016: 406-12.##Budovsky A, Yarmolinsky L and Ben-Shabat S. Effect of medicinal plants on wound healing. Wound Repair Regen 2015; 23: 171-183. https://doi.org/10.1111/wrr.12274##Cañedo-Dorantes L and Cañedo-Ayala M. Skin acute wound healing: a comprehensive review. Int J Inflam 2019; 2019. https://doi.org/10.1155/2019/3706315##Crow D. Frankincense and Myrrh: The botany, culture, and therapeutic uses of the world’s two most important resins.##Di Stefano V, Schillaci D, Cusimano MG, Rishan M and Rashan L. In vitro antimicrobial activity of frankincense oils from Boswellia sacra grown in different locations of the Dhofar region (Oman). Antibiotics 2020; 9: 195. https://doi.org/10.3390/antibiotics9040195##Fahimi S, Hajimehdipoor H, Abdollahi M and Mortazavi SA. Burn healing plants in Iranian traditional medicine. Res j pharmacogn 2015; 2: 53-68.##Faraji A, Aghdaki M, Hessami K, et al. 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