en jalali 1401 6 1 gregorian 2022 9 1 26 3 online 1 fulltext

en Zataria multiflora Boiss L. (Z. multiflora) is belonged to the Lamiaceae family, formerly used for culinary and medicinal purposes. Various pharmacological effects of Z. multiflora such as bronchodilation, effect on lung inflammation, cold and gynecology disorders have been reported. A literature search was performed in the following databases: Science Direct, PubMed, Scopus and Google Scholar. The keywords including “Zataria multiflora Boiss.”, “carvacrol”, “thymol”, “linalool”, “smooth muscle” and “relaxant effects” were searched. The relaxant effects of Z. multiflora and its ingredients on different smooth muscles including trachea, vascular, gastrointestinal and urogenital smooth muscle were demonstrated. The relaxant effect of Z. multiflora on smooth muscles could be of therapeutic importance, such as bronchodilation in obstructive respiratory disorders, vasodilation in hypertension and reliving digestive or urogenital disorders. The possible mechanisms of the relaxant effect of Z. multiflora and its components, mainly carvacrol on smooth muscle such as inhibitory effect on histamine (H1) and muscarinic receptors, calcium channel blocking effects and stimulatory effect on the beta adrenergic receptor were shown. Smooth muscle, Relaxant effect, Zataria multiflora Boiss L, Carvacrol, Thymol, Linalool 213 225 http://ppj.phypha.ir/browse.php?a_code=A-11-828-1&slc_lang=en&sid=1 2020/11/19 1399/8/29 2021/04/26 1400/2/6 Mohammad Reza Khazdair Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran M.khazdair@yahoo.com 00319475328460031273 00319475328460031273 No Zahra Gholamnezhad Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 00319475328460031274 00319475328460031274 No Saeideh Saadat Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran 00319475328460031275 00319475328460031275 No Mohammad Hossein Boskabady Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran boskabadymh@mums.ac.ir 00319475328460031276 00319475328460031276 Yes

en The endoplasmic reticulum (ER) is an important organelle responsible for protein folding, calcium homeostasis and lipid biosynthesis. Accumulation of unfolded or misfolded proteins by hypoxia, loss of Ca2+ homeostasis and nutrient deprivation leads to endoplasmic reticulum stress (ERS) and then the unfolded protein response (UPR) is activated as a defense mechanism to restore endoplasmic reticulum homeostasis. It is now known that the ERS and the UPR are implicated in a variety of diseases such as diabetes, inflammatory diseases, neurodegenerative diseases and osteoporosis. Steroid hormones such as 17-βestradiol have been extensively reported to possess beneficial effects in different diseases. In this article, the concept of ERS, the underlying molecular mechanisms, and their relationship to several pathological conditions and finally, the role of 17-βestradiol and its receptors in moderating ERS and UPR are discussed to provide theoretical basis for in-depth study. Endoplasmic reticulum, 17 β-estradiol, Endoplasmic reticulum stress, Estrogen 226 238 http://ppj.phypha.ir/browse.php?a_code=A-11-1602-1&slc_lang=en&sid=1 2020/11/192021/06/28 1400/4/7 2021/04/262021/08/30 1400/6/8 Zeinab Farhadi Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031277 00319475328460031277 No Mansour Esmailidehaj Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031278 00319475328460031278 No Mohammad Ebrahim Rezvani Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031279 00319475328460031279 No Mohammad Shahbazian Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031280 00319475328460031280 No Faezeh Jafary-nezhad Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031281 00319475328460031281 No Mohammad Amin Ghafari Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031282 00319475328460031282 No Jalil Alizadehghalenoei Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 00319475328460031283 00319475328460031283 No Hossein Azizian Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran H.Azizian@ssu.ac.ir 00319475328460031284 00319475328460031284 Yes

en Introduction: Insulin resistance and low adropin level are two risk factors for comorbidity in overweight individuals. The aim of this study was to investigate whether eight weeks of endurance (ET) and resistance training (RT) could affect adropin and insulin resistance among overweight men. Methods: In this clinical trial, 27 overweight university students (20-28 years of age; 25 29.9) were recruited and randomly allocated into three groups: control (n=9), RT (n=9) and ET (n=9). The RT consisted of eight moves (3 sessions/ week) performed in two sets of 6 repetitions with 30% of 1 repetition maximum (RM) during week 1, and gradually increased to four sets of 6 repetitions with 70% of 1RM by the 8th week. The ET program included treadmill running (3 days/ week) performed during 15-40min for eight weeks with an intensity of 50-80% of the maximum heart rate. Results: The results showed that the levels of adropin in the ET group significantly increased more than that of RT and control group. Moreover, fasting blood insulin and homeostasis model assessment of insulin resistance significantly decreased in both groups, while fasting blood glucose and quantitative insulin-sensitivity check index did not significantly change. Conclusion: It is concluded from the results of this study that eight weeks of ET and RT could help improve the metabolic profile among overweight youngsters. It is also possible that ET is more beneficial in this matter than RT. : Resistance training, Endurance training, Insulin resistance, Adropin, overweight. 239 247 http://ppj.phypha.ir/browse.php?a_code=A-10-1567-1&slc_lang=en&sid=1 2020/11/192021/06/282021/04/7 1400/1/18 2021/04/262021/08/302021/06/19 1400/3/29 Elaheh Akhavan Rasoolzadeh Department of Exercise Physiology, Faculty of Sports Sciences, Alzahra University, Tehran, Iran 00319475328460031285 00319475328460031285 No Parvaneh Nazarali Department of Exercise Physiology, Faculty of Sports Sciences, Alzahra University, Tehran, Iran 00319475328460031286 00319475328460031286 No Rostam Alizadeh Department of Sports Science, School of Literature and Humanities, Ilam University, Ilam, Iran r.alizadeh@ilam.ac.ir 00319475328460031287 00319475328460031287 Yes

en Introduction: Each undergraduate medical student embarks upon a unique learning journey. A few students achieve their targets smoothly but some land in the group labeled low achievers. We aimed to identify the low achievers, determine their problems, identify their learning preferences and then address these using appropriate remedial measures, thus creating a customized student inventory. Methods: Low achievers were categorized into study and control groups. The study group students’ learning problems were categorized into cognitive, affective, interpersonal and structural domains based on their responses to a questionnaire and were allotted to a faculty in-charge, who identified their learning preferences based on the VARK questionnaire. Customized remedial measures were administered to the study group. Academic performances of both study group and control group students were compared. Results: The majority of students of the study group had affective problems, inability to understand the subject with their method of learning, mismanagement of time, problems in interacting with students and teachers. The study group preferred a multimodal approach to learning. Following the implementation of the inventory among study group students, there was a significant improvement in their academic performance when compared with their previous examination results. The academic performance significantly improved with a large effect size in study group when compared to the control group. Conclusion: Understanding the problems of each medical undergraduate low achiever student, applying customized student inventory with targeted remedial measures directed at their learning problems and preferred mode of learning enabled a smooth transition of low achievers to advanced learners. Academic performance, Learning, Medical Students, Teaching 248 258 http://ppj.phypha.ir/browse.php?a_code=A-10-1524-1&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/16 1399/10/27 2021/04/262021/08/302021/06/192021/06/28 1400/4/7 Grrishma Balakrishnan Department of Physiology, Yenepoya Medical College, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India 00319475328460031288 00319475328460031288 No Aswini Dutt R Department of Physiology, Yenepoya Medical College, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India drdutt23@yenepoya.edu.in 00319475328460031289 00319475328460031289 Yes Shobith Bangera Department of Physiology, Yenepoya Medical College, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India 00319475328460031290 00319475328460031290 No Padmini Thalenjeri Department of Physiology, Yenepoya Medical College, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India 00319475328460031291 00319475328460031291 No Kalpana Balasubramaniyam Department of Physiology, Yenepoya Medical College, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India 00319475328460031292 00319475328460031292 No Ahrsia Valavoor Fathima Department of Physiology, Yenepoya Medical College, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India 00319475328460031293 00319475328460031293 No

en Introduction: People mainly have a major interest in eating some palatable foods such as chocolate and sweet foods that influence brain functions. This study investigated the effects of acute, sub-chronic and chronic chocolate consumption with different percent of cocoa/sugar on learning, memory, memory consolidation and electroencephalogram (EEG) waves in rats. Methods: Thirty-five male Wistar rats were allocated to five main groups containing control and sucrose as well as dark, milk and white chocolate groups. All groups were freely fed with chow, different kinds of chocolate and sucrose separately for 1,7 and 14 days as acute, sub-chronic and chronic food consumption. Also, memory and memory consolidation were evaluated using a passive avoidance test on days 1,7 and 14. In addition, brain electrical activity was evaluated by EEG. Results: Acute and sub-chronic dark and milk chocolate consumption significantly improved latency after day 1 and particularly day 7. In addition, only the chronic dark chocolate diet showed a significant enhancement in latency after 14 days. White chocolate and sucrose diets did not have significant effects on three latencies. The milk and dark chocolate diets changed nearly all brain waves of EEG, while the sucrose diet did not affect any of them. Conclusion: Unlike sucrose and white chocolate, dark chocolate (acute, sub-chronic and chronic consumption) and milk chocolates (acute and sub-chronic consumption) had beneficial effects on memory and nearly all electrical brain activity probably due to high levels of cocoa and perhaps its antioxidant effect. Hence, these types of diets modified brain homeostasis and increased conscious state and relaxation reduction. Chocolate, Memory, EEG, Sugar, Rats. 259 271 http://ppj.phypha.ir/browse.php?a_code=A-10-895-9&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/12 1400/1/23 2021/04/262021/08/302021/06/192021/06/282021/06/21 1400/3/31 Ghazaleh Hadian Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 00319475328460031294 00319475328460031294 No Maryam Radahmadi Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 00319475328460031295 00319475328460031295 Yes Hojjatallah Alaei Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 00319475328460031296 00319475328460031296 No Parham Reisi Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 00319475328460031297 00319475328460031297 No

en Introduction: Alzheimer’s disease (AD) is a progressive and chronic neurodegenerative disorder in which amyloid-β (Aβ) and hyperphosphorylated-tau (P-tau) are well-established pathological hallmarks. Carbamylated erythropoietin (CEPO-Fc) is one of the erythropoietin derivatives with neuroprotective properties against neurodegenerative disorders. However, the underlying molecular mechanism of CEPO-Fc has not been fully elucidated. Therefore, we investigated the therapeutic effects of CEPO-Fc on Aβ-induced neurotoxicity in the in-vivo rat model. Methods: Adult male Wistar rats were cannulated in the dorsal hippocampus and Aβ25-35 was microinjected for four consecutive days. CEPO-Fc was administered intranasally during the next six consecutive days. Learning and memory performance were examined (days 10-13) using the Morris water maze test. Furthermore, the hippocampal levels of critical proteins involved in apoptosis (Bax, Bcl-2 and caspase-3), necroptosis (phosphorylatedreceptor-interacting serine/threonine-protein kinase 3) and autophagy (p-Beclinbeclin-1 and phosphorylated- 1A/1B-light chain 3) were assessed using immunoblotting. Results: Behavioral analysis showed that CEPO-Fc treatment significantly improved Aβ-induced learning and memory impairment. Furthermore, the hippocampus’s molecular analysis showed that CEPO-Fc induced up-regulation of the autophagic proteins, p-Beclin-1 and p-LC3-II, while decreased caspase-3, Bax/Bcl2 ratio as well as the necroptosis factor p-RIP3. Conclusion: Our results indicate that the neuroprotective properties of CEPO-Fc in animal model of AD could be mediated by autophagy activation and inhibition of apoptosis and necroptosis processes. This study introduces CEPO-Fc as a potential protective compound against AD and other neurodegenerative disorders. Alzheimer's disease, CEPO-Fc, Apoptosis, Autophagy, Necroptosis 272 287 http://ppj.phypha.ir/browse.php?a_code=A-10-1604-1&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/122021/06/30 1400/4/9 2021/04/262021/08/302021/06/192021/06/282021/06/212021/08/7 1400/5/16 Amirhossein Maghsoudi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 00319475328460031298 00319475328460031298 No Jalal Zaringhalam Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran jzaringhalam@sbmu.ac.ir 00319475328460031299 00319475328460031299 Yes Maryam Moosavi Nanomedicine and Nanobiology Research Centre, Shiraz University of Medical sciences, Shiraz, Iran 00319475328460031300 00319475328460031300 No Akram Eidi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 00319475328460031301 00319475328460031301 No

en Introduction: Methamphetamine (METH) addiction is an epidemic-growing problem globally. Studies confirmed a solid linkage between the prefrontal cortex (PFC) and drug seeking. The present study aimed to investigate PFC neural activity changes after injection of METH following METH-induced conditioned place preference (CPP) in the rats. Methods: After the development of CPP (0.5mg/kg METH for three days, SC), in vivo single-unit recordings were carried out the day after the post-test (post-conditioning day). On recording day, after stabilization and baseline recording (a 10-min period), the injection of METH (0.5mg/kg, SC) was performed and then, PFC neural activity was recorded for a 30-min period. Results: The results revealed that the injection of METH on the post-conditioning test significantly increases PFC neurons’ firing rate in animals that received METH during the CPP paradigm. Conclusion: It seems that maybe, PFC neurons appear to be implicated in the associated METH reward pathway and repeated exposure to METH affected the sensitivity of neurons in this area. Reward system, Prefrontal cortex, Methamphetamine, Neuronal activity, Conditioned place preference 288 298 http://ppj.phypha.ir/browse.php?a_code=A-10-1513-2&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/122021/06/302021/02/21 1399/12/3 2021/04/262021/08/302021/06/192021/06/282021/06/212021/08/72021/07/26 1400/5/4 Zahra Taslimi Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 00319475328460032679 00319475328460032679 No Abdolrahman Sarihi Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran 00319475328460032680 00319475328460032680 No Sara Karimi Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 00319475328460032681 00319475328460032681 No Abbass Haghparast Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Haghparast@yahoo.com 00319475328460032682 00319475328460032682 Yes

en Introduction: Phenylhydrazine (PHZ)-induced anaemia is associated with oxidative damage to erythrocytes and impaired renal function. Fresh palm oil (FPO) is a rich source of antioxidants and preserves renal function. This study investigated the possible reno-protective effects of FPO in PHZ-induced anaemic Wistar rats. Methods: Eighteen male Wistar rats were randomly assigned into normal control (NC), anaemic control (AC; 60mg/kg of PHZ) and anaemic treated (A+FPO; 60mg/kg of PHZ + 15% FPO diet) groups. PHZ was administered twice consecutively at 48h interval while FPO diet was given throughout the study period (14 days). Results: Erythrocyte count, haemoglobin concentration and haematocrit were increased in A+FPO compared with AC. FPO improved imbalances in the levels of glucose and electrolytes (Na+, Cl-, K+, HCO3-) in serum and urine of the anaemic rats. Urea and creatinine concentrations were decreased in serum and increased in urine in the A+FPO relative to AC. Proteinuria was decreased in A+FPO compared with AC. The levels of malondialdehyde, proinflammatory cytokines and caspase-3 were down-regulated in A+FPO compared with AC while interleukin-10 concentration, enzymatic antioxidants activities and total antioxidant capacity were up-regulated in A+FPO compared with AC. Conclusion: FPO demonstrated anti-anaemic effect and improved the impaired renal function associated with PHZ-induced anaemia. Anaemia, Fresh palm oil, Haemolysis, Phenylhydrazine, Renal function 299 312 http://ppj.phypha.ir/browse.php?a_code=A-10-1447-1&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/122021/06/302021/02/212020/09/17 1399/6/27 2021/04/262021/08/302021/06/192021/06/282021/06/212021/08/72021/07/262021/07/26 1400/5/4 Ernest Atelhe Amama Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031306 00319475328460031306 No Augustine Lishilinimye Udefa Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria augustineudefa@unical.edu.ng 00319475328460031307 00319475328460031307 Yes Favour Nyoh Beshel Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031308 00319475328460031308 No Efiok Aniekan Archibong Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031309 00319475328460031309 No Sunday Okpa Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031310 00319475328460031310 No Justina Nwandimma Nwangwa Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031311 00319475328460031311 No Ndianabasi Isidore Felix Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031312 00319475328460031312 No Godwin Akronyi Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria 00319475328460031313 00319475328460031313 No

en Introduction: Acrylamide (ACR) is a toxic substance that has renal toxicity. We aim to investigate the therapeutic activity of ellagic acid (EA) on renal injury induced by ACR in Wistar rats. Methods: Thirty-five male Wistar rats were assigned into 5 groups: the control group (5ml/kg normal saline), the ACR group (20mg/kg ACR), the ACR+EA10 group (ACR and 10mg/kg EA), the ACR+EA30 group (ACR and 30mg/kg EA) and the EA30 group (30mg/kg EA). ACR and EA were daily administered by gavage for 30 days. Renal function was assessed by measuring the sera levels of creatinine (Cr) and blood urea nitrogen (BUN). Renal oxidative and inflammatory markers including malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). hematoxylin and eosin staining was employed to assess pathological alternations of the kidney. Results: EA (more potentially 30mg/kg) administration alleviated the ACR-induced alterations in Cr and BUN levels. Moreover, EA treatment reduced the elevated levels of MDA, NO and PC as well as TNF-α and IL-1β content in renal tissue. Furthermore, reduced activity of SOD and CAT as well as GSH content in the kidney was increased by EA treatment. EA attenuated the ACR- induced pathological alterations in kidney. Conclusion: These findings suggested that EA could mitigate ACR-induced kidney injury due to its potent antioxidant and anti-inflammatory effects. Acrylamide, Oxidative stress, Inflammation, Nephrotoxicity, Ellagic acid 313 321 http://ppj.phypha.ir/browse.php?a_code=A-10-873-3&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/122021/06/302021/02/212020/09/172021/02/24 1399/12/6 2021/04/262021/08/302021/06/192021/06/282021/06/212021/08/72021/07/262021/07/262021/08/30 1400/6/8 Saeed Mehrzadi Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran 00319475328460031314 00319475328460031314 No Mohammad Amin Mombeini Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 00319475328460031315 00319475328460031315 No Iman Fatemi Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran 00319475328460031316 00319475328460031316 No Heibatullah Kalantari Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 00319475328460031317 00319475328460031317 No Mojtaba Kalantar Shoushtar Faculty of Medical Sciences, Shoushtar, Iran 00319475328460031318 00319475328460031318 No Mehdi Goudarzi Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Goudarzi-M@ajums.ac.ir 00319475328460031319 00319475328460031319 Yes

en Introduction: Pain is an unpleasant and annoying sensation caused by tissue damage and inflammatory stimuli. Due to the side effects of the conventional drugs, the present study was conducted to investigate the antinociceptive effects of Onosma platyphyllum (OP) and its antioxidant activity. Methods: The OP hydroethanolic extract was evaluated by gas chromatography–mass spectrometry (GC-MS) analysis. The phenolic and flavonoid content respectively were determined by Folin-Ciocalteu and aluminum chloride assays. The antioxidant activity of the extract was evaluated by FRAP and DPPH methods. Formalin test was also used to evaluate the herbal antinociceptive effects on various doses (50, 100, 150 and 200mg/kg). Results: The content of β-phenylethyl butyrate, 2-pentanone,4-hydroxy-4-methyl, 3’-acetyllycopsamine and indolizine analysed by GC-MS were 25.9%, 8.86%, 8.5% and 5.52% of the extract respectively. The phenolic and flavonoid content of the extract were 45.20±2.75 µgGAE/mg and 184.40±26.23 µgQE/mg. The monovalent reducing activity was 382.35±34.83 μMFe2+. The radical scavenging activity of the extract in the dose of 500µg/mL was also 13.71±3.67. The acute and chronic pain score was significantly reduced in treatment with OP extract. The chronic antinociceptive effects of the extract were higher than acute effects. The highest antinociceptive effect was related to 200mg/kg concentration of the extract. Conclusion: OP is effective in pain relieving, especially in the chronic phase probably by improving the oxidative stress. It’s side effects and hepatotoxicity should be evaluated. Pain, Nociceptive, Antioxidants, Plant extracts, Onosma platyphyllum. 322 332 http://ppj.phypha.ir/browse.php?a_code=A-10-1548-1&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/122021/06/302021/02/212020/09/172021/02/242021/02/20 1399/12/2 2021/04/262021/08/302021/06/192021/06/282021/06/212021/08/72021/07/262021/07/262021/08/302021/09/25 1400/7/3 Kamran Ranjbar Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran 00319475328460031331 00319475328460031331 No Alireza Moulazadeh Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran a.moulazadeh@fums.ac.ir 00319475328460031332 00319475328460031332 No Amin Dakhili Ardestani Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran 00319475328460031333 00319475328460031333 No Mohammad Soleimanian Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran 00319475328460031334 00319475328460031334 No Zakaria Meshkibaf DIPSAR, Delhi Pharmaceutical Sciences and Research University, New Delhi, India 00319475328460031335 00319475328460031335 No Mohammad Hassan Meshkibaf Department of Clinical Biochemistry, Fasa University of Medical Sciences, Fasa, Iran meshkibaf.m@fums.ac.ir 00319475328460031336 00319475328460031336 Yes

en Introduction: Breast cancer is one of the important causes of mortality among women. Many studies have focused on the development of natural health products for prevention and treatment of breast cancer. This study investigated the effects of Bifidobacterium bifidum and its microvesicles (MVs) on 4T1-induced breast cancer in BALB/c mice. Methods: Sixty female BALB/c mice were divided into 5 groups: (1) negative control, (2) positive control, (3) doxorubicin, (4) probiotic and (5) MVs (isolated from B. bifidum). The mice in groups 4 and 5 were pretreated with B. bifidum and MVs for 4 weeks, respectively. Tumor was induced by subcutaneous administration of 4T1 cell culture. After tumor development, mice in group 3 were treated with doxorubicin while other groups were treated as before. The mice were sacrificed after 3 weeks, breast tumors were removed and histologically examined. Also, P53 and Ki67 protein were evaluated by immunohistochemistry staining, and P53 gene expression was assessed by RT-PCR. Results: Pretreatment with MVs and probiotic reduced mortality and tumor growth rate. MVs and Probiotic prevented the weight loss and suppressed tumor cell proliferation which was indicated by Ki-67 and p53. The expression of p53 confirmed these results. Despite the malignancy in the breast tissue, necrosis of cancer cells occurred in the mice treated with MVs. Conclusion: MVs of B. bifidum effectively inhibited breast cancer development in mice and suppressed tumor cell proliferation. Probiotic microorganisms and their metabolites can be used as a functional food to prevent breast cancer. Triple negative breast cancer, Probiotic, Bifidobacterium bifidum, Microvesicles, Ki67, p53 333 344 http://ppj.phypha.ir/browse.php?a_code=A-10-1421-1&slc_lang=en&sid=1 2020/11/192021/06/282021/04/72021/01/162021/04/122021/06/302021/02/212020/09/172021/02/242021/02/202020/07/30 1399/5/9 2021/04/262021/08/302021/06/192021/06/282021/06/212021/08/72021/07/262021/07/262021/08/302021/09/252021/06/19 1400/3/29 Farzanrh Nazari Microbiology Department, Science Faculty, Islamic Azad University , Arak Branch, Arak, Iran 00319475328460031326 00319475328460031326 No Parvaneh Jafari Microbiology Department, Science Faculty, Islamic Azad University , Arak Branch, Arak, Iran p-jafari@iau-arak.ac.ir 00319475328460031327 00319475328460031327 Yes Bizhan Nomanpour School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran 00319475328460031328 00319475328460031328 No Kamibiz Varmira Research Center of Oils and Fats, Kermanshah University of Medical sciences, Kermanshah, Iran 00319475328460031329 00319475328460031329 No Farshid Reissi School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran 00319475328460031330 00319475328460031330 No