Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Strategies for Stem Cell-Based Therapy for Inner Ear Cochlear Regeneration 331 344 EN ali asghar Peyvandi Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Hojjat-Allah Abbaszadeh Department of Anatomical Sciences and Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Shahrokh Khoshsirat Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Alireza Zali Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran,Iran somayeh niknazar 1.Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 The therapeutic effects of erythropoietin and carbamylated erythropoietin derivatives in neurological and other disorders 345 356 EN Amirhossein Maghsoudi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Jalal Zaringhalam Faculty member of Physiology Department, School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran Maryam Moosavi Nanomedicine and Nanobiology Research Centre, Shiraz University of Medical sciences, Shiraz, Iran Akram Eidi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Herbal treatment options for female fertility disorders: a systematic review of clinical trials 357 386 EN Izuchukwu Azuka Okafor Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, PMB 5001, Nnewi, Nigeria Ndubuisi Paris Obi Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, PMB 5001, Nnewi, Nigeria Kingsley Chinemerem Ibeabuchi College of Nursing Sciences, Our Lady of Lourdes Hospital Complex, Ihiala, Anambra State, Nigeria 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 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 387 391 EN Brajesh Sharma MPMSU JABALPUR, India Sanjeev Kumar Shrivastava mpmsu jabalpur, India Nandini Shukla MPMSU Jabalpur, India Rashmi Dave MPMSU JABALPUR MADHYA PRADESH, India Asha Shrivastava MPMSU Jabalpur, India 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Neuroprotective effect of Acorus calamus Linn. extract on a rat model of chronic constriction injury of median nerve-induced peripheral neuropathy 392 402 EN Shubhechha Bansod Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune Likhit Akotkar Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune, India Subhash Bodhankar Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune, India Urmila Aswar Associate Professor, Bharati Vidyapeeth (Deemed to be University) Poona College of Pharmacy, Pune, India 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Safranal Ameliorates Ischemic/Reperfusion Injury Induced by Testicular Torsion in Rat 403 416 EN Marzieh Ebrahimi Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran Seyed-Hosein Abtahi-Evari Department of Biochemistry, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Balal Brazvan Department of anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Majid Shokoohi Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Malihe Soltani Department of anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Morteza Rostamian English department, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Masoumeh Fani Department of anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran Maryam Moghimian Department of Physiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Diverse long-term exercise intensity effects on appetite and body weight regulation: Arcuate Neuropeptide -Y and Proopiomelanocortin gene function 417 425 EN Nazli Khajehnasiri Assistant Professor in Animal Physiology, Higher Education Institute of Rab-Rashid, Tabriz, Iran mostafa hosseini Department of Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran Parivash Piraki Dareh Shahr Branch, Islamic Azad University, Dareh Shahr, Iran Mahnaz Ghowsi Department of biology, Faculty of Sciences, Razi University, Kermanshah, Iran Leila Rahbarnia Tabriz University of Medical Sciences, Tabriz, Iran Parisa Habibi Assistant Professor of Physiology, Hamadan University of Medical Sciences, Hamadan, Iran Reihaneh Sadeghian Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Investigating the effects of Lactobacillus acidophilus and Lactobacillus paracasei supernatant on cervical cancer cells 426 434 EN Iman Samiei Mosleh Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Fatemeh Karami Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran Iman Salahshourifar Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Maryam Tajabadi Ebrahimi Department of Biology Central Tehran Branch Islamic Azad University Tehran Iran Mohsen Marvibaigi 4 Department Biology, Kavian Institute of higher education, Mashhad, Iran 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.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 27 4 2023 12 1 Wound Healing Effects of Frankincense and Myrrha on Adult Human Dermal Fibroblasts (HDFa) 435 444 EN Atefeh Kavousi Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical, Mashhad, Iran Elham Nikkhah Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Zahra Tayarani-Najaran Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences Behjat Javadi Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical, Mashhad, Iran 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.