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Rasti Boroojeni F, Mashayekhan S, Abbaszadeh HA, Ansarizadeh M, Khoramgah MS, Rahimi Movaghar V. Int J Nanomedicine. 2020;15:3903–3920. Page 3908, left column, Isolation and Characterization of BMSCs section, the text “Afterward, PBS was used to wash the fixed cells twice and the cells were incubated at 4°C with antibodies specific for the following antigens: CD34, CD45, CD90, CD44, Nestin, NF68, GFAP for 30 mins” should read “Afterward, PBS was used to wash the fixed cells twice and the cells were incubated at 4°C with antibodies specific for the following antigens: CD45, CD29, CD73, CD105, Nestin, NF68, GFAP for 30 mins”. Page 3909, right column, the section heading “Static Analysis” should read “Statistical Analysis”. Figure 2 on page 3910, the scale bar in part E shows “2 ìM” it should read “10 ìm”. The text “(the condition and concentration of PCL nanofibers was exactly the same for all four groups, thus the same SEM image was used to show the PCL nanofibers for all groups)” has also been added to the figure caption. The correct Figure 2 is shown. Page 3911, BMSCs Characterization section, the text “In this analysis, CD44, CD90, and CD 106 markers as mesenchymal stem cell markers and CD45 as hematopoietic stem cells marker were used” should read “In this analysis, CD29, CD73, and CD 105 markers as mesenchymal stem cell markers and CD45 as hematopoietic stem cells marker were used”. Figure 3 on page 3912, the scale bar in part C shows “20 μM” it should read “20 μm”. The correct Figure 3 is shown. Figure 5 on page 3914, the scale bar in part A shows “10 μM” it should read “10 μm”. The text “(the condition and concentration of gelatin nanofibers was exactly the same for PG/PAG 2, PG/PAG 2/1% NP, PG/PAG 2/2% NP, and PG/PAG 2/3% NP %, thus the same SEM image was used to show the gelatin nanofibers for all groups)” has also been added to the figure caption. The correct Figure 5 is shown. The authors have advised there is an error in the caption of Figure 7 on page 3916. The text “scale bar = 20 μM” should read “scale bar = 20 μm”. Figure 8 on page 3917, the scale bars in part B shows “μM” they should read “μm”. The correct Figure 8 is shown. The authors apologize for these errors. Read the original article

Huntington's disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cells in the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities including pharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeutic potential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group, a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuously over a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection within an experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and open field assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level in the treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatory and fibrotic factors in the HD model.

Introduction: Heat stress is one of the environmental causes of damage to the testis, whose effects are less known before puberty. The aim of the present study was to investigate the impact of photobiomodulation (PBM) on the testis of prepubertal mice subjected to hyperthermia. Methods: Twenty-four three-week-old prepubertal male mice were allocated to the following groups: I) control, II) scrotal hyperthermia (Hyp), and III) Hyp+PBM (n=8/each group). In order to induce hyperthermia, the scrotum was placed in water at 43 °C for 20 minutes every other day for a total duration of 10 days. In the Hyp+PBM group, after hyperthermia induction, the testis of the mice was subjected to laser irradiation at a wavelength of 890 nm (0.03 J/cm 2 for 30 seconds) for 35 days. After the mice were sacrificed, the testis and epididymis were removed for testing. Results: Compared with those of the Hyp group, the sperm parameters of the laser irradiation group improved notably. In addition, histological examinations revealed that the final number of testis cells and the volume of tissue in the Hyp+PBM group were dramatically greater than those in the Hyp group. The analysis of molecular data revealed an increase in the expression of mitotic genes and testosterone levels and a decrease in the formation of reactive oxygen species (ROS) and the expression of the apoptotic gene in the testis subjected to PBM. Conclusion: Based on the present findings, laser therapy can reduce complications caused by scrotal hyperthermia during prepuberty and ameliorate spermatogenesis during puberty., Competing Interests: All the writers confirm that they have no personal concerns or biases that could affect the findings of this study., (Copyright © 2024 J Lasers Med Sci.)

Introduction: Unhealthy lifestyle choices such as alcohol, chemicals, and heat stress can worsen male infertility. Heat stress can cause damage to the essential structure known as the blood-testis barrier (BTB). Photobiomodulation therapy (PBMT) has been employed in various studies to enhance sperm quality in individuals with genital inflammatory conditions in recent times. The current research sought to study how laser therapy affects spermatogenesis and the structure of the BTB in a mouse model of scrotal heat exposure. Methods: Thirty adult male NMRI mice, 8 weeks old, were divided into three groups: Control, Hyperthermia, and Hyperthermia+Laser 0.03 J/cm 2 . The animals in the hyperthermia group had their testicles exposed to water at 43 °C for 20 minutes five times every other day. Then, the testicles were exposed to laser radiation every other day for 35 days, lasting 3 minutes each time, with an energy density of 0.03 J/cm 2 . Animals were sacrificed, and sperm parameters, reactive oxygen species (ROS) and glutathione (GSH) levels, stereological parameters, and gene expression were assessed in the end. Results: The study showed that PBMT can significantly enhance sperm quality, quantity of spermatogenic cells, testicular volume, levels of ROS and GSH, and gene expression related to the blood-testis barrier. Conclusion: Currently, PBMT is a novel approach for addressing male infertility by preserving the integrity of the BTB in Sertoli cells, which in turn supports the growth and specialization of germ cells., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024 J Lasers Med Sci.)

Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Diabetes is associated with several debilitating complications, including the development of diabetic foot ulcers (DFUs), which can have serious consequences. This study emphasizes a multidisciplinary approach, providing a thorough overview of DFU pathogenesis and available treatments. Methods: An extensive literature review, covering studies published between 2000 and 2023, was conducted to gather data on DFU pathophysiology and treatments, including wound dressings, photobiomodulation, off-loading devices, adjunct medicines, and stem cell therapy. Results: DFUs are complicated due to infection, ischemia, and neuropathy. Sufficient wound dressings maintain a moist environment, promoting autolytic debridement and facilitating the healing process. Through cellular mechanisms, photobiomodulation therapy (PBM) was observed to expedite the healing process. Additionally, off-loading devices were invented to reduce ulcer pressure and promote healing. Adjunct therapies such as negative pressure wound therapy and hyperbaric oxygen therapy were identified as valuable tools for enhancing healing outcomes. Furthermore, autologous and allogeneic stem cell treatments exhibited the potential for promoting tissue regeneration and expediting the healing process. Conclusion: The complex pathophysiology of DFUs necessitates a multimodal treatment approach. Essential components include PBM, wound dressings, off-loading devices, adjunct treatments, and stem cell therapy., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2024 J Lasers Med Sci.)

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Scrotal hyperthermia poses a significant threat to spermatogenesis and fertility in mammalian species. This study investigated the effects of vitamin B12 and vitamin C on spermatogenesis in adult male mice subjected to long-term scrotal hyperthermia. The rationale is based on the sensitivity of germ cells and epididymal sperm to increased scrotal temperatures. While various factors, both internal and external, can raise the testicular temperature, this study focused on the potential therapeutic roles of vitamins B12 and C., Methods: After inducing scrotal hyperthermia in mice, vitamin B12 and vitamin C were administered for 35 days. We assessed sperm parameters, serum testosterone levels, stereological parameters, the percentage of apoptotic cells, reactive oxygen species (ROS) levels, and glutathione (GSH) levels. Additionally, real-time polymerase chain reaction was used to analyze the expression of the c-kit, stimulated by retinoic acid gene 8 (Stra8), and proliferating cell nuclear antigen (Pcna) genes., Results: Vitamin C was more effective than vitamin B12 in improving sperm parameters and enhancing stereological parameters. The study showed a significant decrease in apoptotic cells and a beneficial modulation of ROS and GSH levels following vitamin administration. Moreover, both vitamins positively affected the expression levels of the c-kit, Stra8, and Pcna genes., Conclusion: This research deepens our understanding of the combined impact of vitamins B12 and C in mitigating the effects of scrotal hyperthermia, providing insights into potential therapeutic strategies for heat stress-related infertility. The findings highlight the importance of considering vitamin supplementation as a practical approach to counter the detrimental effects of elevated scrotal temperatures on male reproductive health.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI., Methods: Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24 + renal progenitor cells and evaluate their functional activity in alleviating AKI., Results: The obtained results show that hESCs-derived CD133+CD24 + RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis., Conclusion: The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Introduction: Polycystic ovary syndrome (PCOS) is a complex condition that can have various symptoms and complications, one of which is infertility. Dysregulation of miRNA has been associated with the pathogenesis of numerous illnesses such as PCOS. In this study, we evaluated the effect of photobiomodulation therapy (PBMT) and exosome therapy (EXO) on the regulation of miRNA and nucleus acetylation in a PCOS oocyte. Methods: In this research, 36 oocytes divided into three groups: control, EXO, and PBM (Wavelength of 640 nm). Subsequently, in-vitro maturation (IVM) was evaluated. Real-time PCR was used to evaluate miRNA-21,16,19,24,30,106,155 and GAPDH . Afterward, oocyte glutathione (GSH) and nucleus acetylation were measured by H4K12. Results: The expression of the miR-16, miRNA-19, miRNA-24, miRNA-106 and miRNA-155 genes in the EXO and PBMT groups was significantly down-regulated in comparison to the control group, but the expression of miRNA-21 and miR-30 significantly increased in the EXO and PBMT groups in comparison to the control group. The EXO and PBMT significantly increased GSH and nucleus acetylation ( P <0.0001). Conclusion: The results of this study showed that the use of EXO and PBMT can improve GSH and nucleus acetylation in the PCOS oocyte and also change the expression of miRNAs., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 J Lasers Med Sci.)

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor ( CREB/BDNF ) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3 , and tumor necrosis factor-α [ TNF-α ]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1 , and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3 , and TNF-α . Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

Introduction: In men, several factors cause infertility, among which we can mention damage to sperm due to high temperature. So far, various treatments have been proposed for it, but they have not been highly effective. The current study aimed to evaluate the effect of exosome therapy (EXO) and photobiomodulation therapy (PBMT) on spermatogenesis arrest in male mice after scrotum hyperthermia. Methods: In this experimental study, the animals were divided into four groups: control, scrotal hyperthermia, scrotal hyperthermia+EXO (100 μL/d) (mice were treated for 30 days), scrotal hyperthermia+PBMT (laser of 0.03 J/cm2 for 30 seconds/for 30 days). Hyperthermia was induced by exposure to the temperature of 43 °C for 20 minute every day for 5 times. After 6 weeks, the animals were sacrificed. Results: The treated groups showed a significant increase in sperm parameters, as compared to the hyperthermic groups. Moreover, these favorable effects were observed in relation to the volume of testicular tissue, the number of germ cells, Leydig cells and Sertoli cells, and the level of testosterone. Research on antioxidants showed a significant reduction in oxidized glutathione (GSSG) and reactive oxygen species (ROS) in the treatment groups in comparison to the hyperthermia group ( P <0.001). Also, there has been a significant increase in the amount of hydrogen peroxide enzyme observed in the hyperthermia group as opposed to the treatment group ( P <0.001). Conclusion: These findings show that EXO and PBMT can improve spermatogenesis caused by hyperthermia, reduce ROS and GSSG, and increase glutathione (GSH) and sperm quality., Competing Interests: The authors declare that they have no conflicts of interest related to this study., (Copyright © 2024 J Lasers Med Sci.)

Purpose: Regenerative medicine offers new techniques for osteoarthritis (OA) disorders, especially while considering simultaneous chondral and subchondral regenerations., Methods: Chitosan and hyaluronan were chemically bound as the chondral phase and the osteogenic layer was prepared with alginate and nano-hydroxyapatite (nHAP). These scaffolds were fixed by fibrin glue as a biphasic scaffold and then examined., Results: Scanning electron microscopy (SEM) confirmed the porosity of 61.45±4.51 and 44.145±2.81 % for the subchondral and chondral layers, respectively. The composition analysis by energy dispersive X-ray (EDAX) indicated the various elements of both hydrogels. Also, their mechanical properties indicated that the highest modulus and resistance values corresponded to the biphasic hydrogel as 108.33±5.56 and 721.135±8.21 kPa, despite the same strain value as other groups. Their individual examinations demonstrated the proteoglycan synthesis of the chondral layer and also, the alkaline phosphatase (ALP) activity of the subchondral layer as 13.3±2.2 ng. After 21 days, the cells showed a mineralized surface and a polygonal phenotype, confirming their commitment to bone and cartilage tissues, respectively. Immunostaining of collagen I and II represented greater extracellular matrix (ECM) secretion in the biphasic composite group due to the paracrine effect of the two cell types on each other., Conclusion: For the first time, the ability of this biphasic scaffold to regenerate both tissue types was evaluated and the results showed satisfactory cellular commitment to bone and cartilage tissues. Thus, this scaffold can be considered a new strategy for the preparation of implants for OA., Competing Interests: There is no known conflict of interests between the authors that could impact on the results of the corresponding study., (©2024 The Authors.)

Background: An increase in the temperature of the testis is associated with damage to the epithelium of seminiferous tubules and disruption of sperm production., Objective: The current study aimed to investigate the effect of the Sertoli cell-conditioned medium (SCCM) on the blood-testis-barrier associated genes and spermatogenesis process following scrotal hyperthermia., Materials and Methods: In this experimental study, 40 adult NMRI mice (8 wk, 25-30 gr) were allocated into 4 groups: I) control, II) DMEM (10 μl Dulbecco's Modified Eagle Medium), III) scrotal hyperthermia, and IV) scrotal hyperthermia+SCCM (10 μl SCCM). Hyperthermia was induced by placing the mice scrotum in water at 43 C for 20 min every other day for 10 days. Mice were treated every other day for 5 wk. Then the animals were euthanized, and the tails of epididymis were removed to analyze sperm parameters, testis were taken for stereological assessment, reactive oxygen spices and glutathione levels, and the expression of Ocln , Gja1 , Cdh2 , and Itgb1 ., Results: The results of sperm analysis indicated that SCCM-treated mice significantly increased sperm count and motility and reduced DNA fragmentation. In addition, histological and molecular findings showed that the volume of testicular tissue, the number of germ cells, the glutathione level, and the expression of Ocln , Gja1 , Cdh2 , and Itgb1 genes were significantly increased in the SCCM-treated mice., Conclusion: Findings suggest that growth factors of SCCM stimulate the proliferation and differentiation of germ cells through paracrine effects and upregulate the blood-testis-barrier-associated genes in mice subjected to scrotal hyperthermia., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Aghajanpour et al.)

The mammalian renal organ represents a pinnacle of complexity, housing functional filtering units known as nephrons. During embryogenesis, the depletion of niches containing renal progenitor cells (RPCs) and the subsequent incapacity of adult kidneys to generate new nephrons have prompted the formulation of protocols aimed at isolating residual RPCs from mature kidneys and inducing their generation from diverse cell sources, notably pluripotent stem cells. Recent strides in the realm of regenerative medicine and the repair of tissues using stem cells have unveiled critical signaling pathways essential for the maintenance and generation of human RPCs in vitro. These findings have ushered in a new era for exploring novel strategies for renal protection. The present investigation delves into potential transcription factors and signaling cascades implicated in the realm of renal progenitor cells, focusing on their protection and differentiation. The discourse herein elucidates contemporary research endeavors dedicated to the acquisition of progenitor cells, offering crucial insights into the developmental mechanisms of these cells within the renal milieu and paving the way for the formulation of innovative treatment modalities., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Exosomes are extracellular vesicles (EVs) that originate from endocytic membranes. The transfer of biomolecules and biological compounds such as enzymes, proteins, RNA, lipids, and cellular waste disposal through exosomes plays an essential function in cell-cell communication and regulation of pathological and physiological processes in skin disease. The skin is one of the vital organs that makes up about 8% of the total body mass. This organ consists of three layers, epidermis, dermis, and hypodermis that cover the outer surface of the body. Heterogeneity and endogeneity of exosomes is an advantage that distinguishes them from nanoparticles and liposomes and leads to their widespread usage in the remedy of dermal diseases. The biocompatible nature of these extracellular vesicles has attracted the attention of many health researchers. In this review article, we will first discuss the biogenesis of exosomes, their contents, separation methods, and the advantages and disadvantages of exosomes. Then we will highlight recent developments related to the therapeutic applications of exosomes in the treatment of common skin disorders like atopic dermatitis, alopecia, epidermolysis bullosa, keloid, melanoma, psoriasis, and systemic sclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Methamphetamine (METH) is a highly addictive psychostimulant known for its profound impact on the nervous system. Chronic METH use leads to neurotoxicity characterized by various molecular and structural alterations in the brain. This review article primarily aims to elucidate the mechanisms underlying METH‑induced neurotoxicity. METH's mechanism of action involves the inhibition of dopamine, serotonin, and norepinephrine reuptake, resulting in altered synaptic function. Prolonged METH exposure triggers oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, impaired axonal transport, autophagy, and programmed cell death, ultimately contributing to neurotoxicity. These neurotoxic effects manifest as increased neuronal firing rate, disruptions in intracellular ion balance (Ca2+ and Na+), energy production imbalances, and excessive reactive oxygen species production. The blood‑brain barrier is compromised, leading to structural, functional, and neurochemical alterations, particularly in the fronto‑striatal circuit. While our comprehensive review addresses these intricate molecular and structural changes induced by METH, we also examined the latest therapeutic strategies designed to mitigate neurotoxicity. Our investigation sheds light on the critical need to comprehend the complex pathways underlying METH‑induced neurotoxicity and develop effective treatment approaches.

Introduction: Biophoton emission, the spontaneous release of photons from living cells, has emerged as an attractive field of research in the study of biological systems. Scientists have recently discovered that changes in biophoton emission could serve as potential indicators of pathological conditions. This intriguing phenomenon suggests that cells might communicate and interact with each other through the exchange of these faint but significant light signals. Therefore, the present study introduces intercellular relationships with biophoton release to detect normal and abnormal cell functions to further achieve cellular interactions by focusing on cell and cell arrangement in disease conditions. Methods: Twenty male mice were assigned to control and busulfan groups. Five weeks after the injection of busulfan, the testis was removed, and then the stereological techniques and TUNEL assay were applied to estimate the histopathology of the testis tissue sections. Results: The findings revealed that the ultra-weak biophoton emission in the control group was significantly lower than in the busulfan group. The oligospermia mice model showed that it significantly changed the spatial arrangement of testicular cells and notably decreased the testis volume, length of seminiferous tubules, and the number of testicular cells. The results of the TUNEL assay showed that the percentage of apoptotic cells significantly increased in the busulfan group. Conclusion: The ultra-weak biophoton emission from testis tissue was reduced in oligospermia mice. As a result, the decline of ultra-weak biophoton can indicate a change in cell arrangement, a decrease in intercellular interaction, and eventually disease., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 J Lasers Med Sci.)

Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Introduction: Diabetes poses a global health challenge, giving rise to various complications, including diabetic foot ulcers (DFUs). DFUs, marked by ischemic ulcers susceptible to infection and amputation, underscore the urgency for innovative treatments. This study investigated the impact of photobiomodulation therapy (PBT) and autologous platelet gel (APG) on DFUs recovery. Methods: We systematically searched Web of Science, EMBASE, MEDLINE, Cochrane Library, Scopus, and Google Scholar (2015-2023) by using pertinent terms like "photobiomodulation therapy," "low level light therapy," and "platelet gel." After meticulous data extraction and review, 57 articles were chosen and categorized. Among these, three randomized controlled trials involving 186 participants were selected for APG analysis. Results: Findings demonstrate that APG application carries minimal risk and offers promising improvements in healing time, grade, pain reduction, and granulation tissue formation. Similarly, diverse PBT modalities involving distinct probes and wavelengths exhibit the potential to enhance tissue perfusion, expedite healing, and impede wound progression, reducing the need for invasive interventions. Conclusion: PBT and APG emerge as valuable tools to augment wound healing, mitigate inflammation, and avert amputation, representing compelling therapeutic options for DFUs., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2023 J Lasers Med Sci.)

Acetyl-11-keto-beta-boswellic acid (AKBA), a potent anti-inflammatory compound purified from Boswellia species, was investigated in a preclinical study for its potential in preventing and treating non-alcoholic fatty liver disease (NAFLD), the most common chronic inflammatory liver disorder. The study involved thirty-six male Wistar rats, equally divided into prevention and treatment groups. In the prevention group, rats were given a high fructose diet (HFrD) and treated with AKBA for 6 weeks, while in the treatment group, rats were fed HFrD for 6 weeks and then given a normal diet with AKBA for 2 weeks. At the end of the study, various parameters were analyzed including liver tissues and serum levels of insulin, leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β), interferon gamma (INF-ϒ), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Additionally, the expression levels of genes related to the inflammasome complex and peroxisome proliferator-activated receptor gamma (PPAR-ϒ), as well as the levels of phosphorylated and non-phosphorylated AMP-activated protein kinase alpha-1 (AMPK-α1) protein, were measured. The results showed that AKBA improved NAFLD-related serum parameters and inflammatory markers and suppressed PPAR-ϒ and inflammasome complex-related genes involved in hepatic steatosis in both groups. Additionally, AKBA prevented the reduction of the active and inactive forms of AMPK-α1 in the prevention group, which is a cellular energy regulator that helps suppress NAFLD progression. In conclusion, AKBA has a beneficial effect on preventing and avoiding the progression of NAFLD by preserving lipid metabolism, improving hepatic steatosis, and suppressing liver inflammation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Polycystic ovary syndrome (PCOS) is the communal endocrine illness in women and the most common cause of infertility due to lack of ovulation. The exact cause of PCOS is still unknown. Affected women may have difficulty getting pregnant due to ovulation problems. Various methods have not been effective in the treatment of PCOS due to the positive role of photobiomodulation therapy (PBMT) and extracellular vesicles (ECV) obtained from cord blood plasma in the treatment of various diseases. The aim of this study was to study the role of ECV and PBMT in maturation and improvement of infertility in women with PCOS. Methods: In this research, a number of oocytes were obtained after ovarian stimulation from women who had been referred to the hospital for infertility treatment after obtaining personal consent, and they were divided into three groups: control, ECV and PBMT. Subsequently, in vitro maturation (IVM) was assessed, then some oocytes were cultured with a routine medium and others were treated with ECV and PBMT. Real-time PCR was used to evaluate BCL-2, BAX, caspase-3, and autophagy gene (ATG5, LC3, Beclin 1). Oocyte glutathione (GSH), oxidised gluathione (GSSG), and reactive oxygen species (ROS) were measured. Results: The metaphase II (MII) oocyte ratio formation significantly increased in the ECV and PBMT groups ( P <0.05). The expression of the BCL-2 gene was significantly up-regulated in the ECV and PBMT groups, but the expression of BAX and caspase-3 significantly decreased ( P <0.05). The expression of the ATG5, LC3, BECLIN-2 genes significantly decreased in the ECV and PBMT groups ( P <0.05). ROS, GSSG decreased in ECV and PBMT groups but GSH increased ( P <0.05). Conclusion: The use of ECV and PBMT can increase the rate of fertilization and maturation of an oocyte and cause a decrease in apoptosis, autophagy, and ROS in a PCOS oocyte., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2023 J Lasers Med Sci.)

Despite significant advancements in tissue engineering and regenerative medicine during the last two decades, the fabrication of proper scaffolds with appropriate cells can still be considered a critical achievement in this field. Hypoxia is a major stumbling block to chronic wound healing, which restrains tissue engineering plans because a lack of oxygen may cause cell death. This study evaluated the cocultured human keratinocytes and human adipose-derived mesenchymal stem cells (AMSCs) on a multilayer oxygen-releasing electrospun scaffold based on PU/PCL.Sodium percarbonate (SPC)-gelatin/PU. The scaffold was characterized using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) methods. Flow cytometry confirmed mesenchymal stem cells, and then the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and DAPI staining were used to assess the in vitro biocompatibility of the scaffold. The experimental results showed that the multilayer electrospun scaffold containing 2.5% SPC could efficiently produce oxygen. Furthermore, according to cell viability results, this structure makes a suitable substrate for the coculture of keratinocytes and AMSCs. Gene expression analysis of various markers such as Involucrin, Cytokeratin 10, and Cytokeratin 14 after 14 days confirmed that keratinocytes and AMSCs coculture on PU/PCL.SPC-gelatin/PU electrospun scaffold promotes dermal differentiation and epithelial proliferation compared to keratinocytes single-cell culture. Therefore, our study supports using oxygen-releasing scaffolds as a potential strategy to hasten skin tissue regeneration. Based on the results, this structure is suggested as a promising candidate for cell-based skin tissue engineering. Given that the developed oxygen-generating polymeric electrospun scaffolds could be used as part of a future strategy for skin tissue engineering, the PU/PCL.SPC-gelatin/PU hybrid electrospun multilayer scaffold in combination with keratinocyte/AMSC coculture is proposed as an effective substrate for skin tissue engineering and regenerative medicine platforms., (© 2023 John Wiley & Sons Ltd.)

Testicular heat stress leads to impairment of spermatogenesis in mammals. Involved mechanism in this vulnerability to heat-induced injury remains unclear, and research is being conducted to find an approach to reverse spermatogenesis arrest caused by hyperthermia. Recently, different studies have utilized photobiomodulation therapy (PBMT) therapy for the improvement of sperm criteria and fertility. This study aimed at evaluating the effect of PBMT on the improvement of spermatogenesis in mouse models of hyperthermia-induced azoospermia. A total of 32 male NMRI mice were equally divided into four groups consisting of control, hyperthermia, hyperthermia + Laser 0.03 J/cm 2 , and hyperthermia + Laser 0.2 J/cm 2 . To induce scrotal hyperthermia, mice were anesthetized and placed in a hot water bath at 43 °C for 20 min for 5 weeks. Then, PBMT was operated for 21 days using 0.03 J/cm 2 and 0.2 J/cm 2 laser energy densities in the Laser 0.03 and Laser 0.2 groups, respectively. Results revealed that PBMT with lower intensity (0.03 J/cm 2 ) increased succinate dehydrogenase (SDH) activity and glutathione (GSH)/oxidized glutathione (GSSG) ratio in hyperthermia-induced azoospermia mice. At the same time, low-level PBMT reduced reactive oxygen species (ROS), mitochondrial membrane potential, and lipid peroxidation levels in the azoospermia model. These alterations accompanied the restoration of spermatogenesis manifested by the elevated number of testicular cells, increased volume and length of seminiferous tubules, and production of mature spermatozoa. After conducting experiments and analyzing the results, it has been revealed that the use of PBMT at a dosage of 0.03 J/cm 2 has shown remarkable healing effects in the heat-induced azoospermia mouse model., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Variation during practice is widely accepted to be advantageous for motor learning and is, therefore, a valuable strategy to effectively reduce high-risk landing mechanics and prevent primary anterior cruciate ligament (ACL) injury. Few attempts have examined the specific effects of variable training in athletes who have undergone ACL reconstruction. Thereby, it is still unclear to what extent the variations in different sensor areas lead to different effects. Accordingly, we compared the effects of versatile movement variations (DL) with variations of movements with emphasis on disrupting visual information (VMT) in athletes who had undergone ACL reconstruction. Forty-five interceptive sports athletes after ACL reconstruction were randomly allocated to a DL group (n = 15), VT group (n = 15), or control group (n = 15). The primary outcome was functional performance (Triple Hop Test). The secondary outcomes included dynamic balance (Star Excursion Balance Test (SEBT)), biomechanics during single-leg drop-landing task hip flexion (HF), knee flexion (KF), ankle dorsiflexion (AD), knee valgus (KV), and vertical ground reaction force (VGRF), and kinesiophobia (Tampa Scale of Kinesiophobia (TSK)) assessed before and after the 8 weeks of interventions. Data were analyzed by means of 3 × 2 repeated measures ANOVA followed by post hoc comparison (Bonferroni) at the significance level of p ≤ 0.05. Significant group × time interaction effects, main effect of time, and main effect of group were found for the triple hop test and all eight directions, SEBT, HF, KF, AD, KV, VGRF, and TSK. There was no significant main effect of group in the HF and triple hop test. Additionally, significant differences in the triple hop test and the seven directions of SEBT, HF, KF, KV, VGRF, and TSK were found between the control group and the DL and VMT groups. Between group differences in AD and the medial direction of SEBT were not significant. Additionally, there were no significant differences between VMT and the control group in the triple hop test and HF variables. Both motor learning (DL and VMT) programs improved outcomes in patients after ACL reconstruction. The findings suggest that DL and VMT training programs lead to comparable improvements in rehabilitation.

Introduction: Chronic and progressive damage to the kidney by inflammatory processes, may lead to an increase in the extracellular matrix production, a condition known as renal fibrosis. The current study aims to evaluate if the extracellular vesicles (EVs) derived from autophagic adipose-derived mesenchymal stem cells (ADMSCs) can reduce the inflammation and extracellular matrix accumulation in damaged kidney tissue., Methods: Autophagy was induced in ADMSCs using 2µM concentration curcumin and was confirmed by evaluating LC3B, ATG7, and Beclin1 using real-time polymerase chain reaction (PCR) and Western blot. An in vitro renal fibrotic model was established in HEK-293 cells exposed to H2O2 (0.8mM) for 24 and 72 hours. The fibrotic model was confirmed through evaluation of collagen I, transforming growth factor-beta 1 (TGF-β1), E-cadherin, and vimentin genes expression using real-time PCR, collagen I protein by ELISA. After induction of fibrosis for 24 and 72 hours, the HEK cells were treated with NEVs (non-autophagy EVs) (50µM) or AEVs (autophagy EVs) (50µM) at 48, 96, and 124 hours, and then the samples were collected at 72 and 148 hours. Expression of collagen I, TGF-β1, E-cadherin, and vimentin Genes was evaluated via RT-PCR, and protein levels of IL1, TNF-α, IL4, IL10 using ELISA., Results: Induction of autophagy using curcumin (2µM) for 24 hours significantly increased LC3B, Beclin1, and ATG7 in the ADMSCs. Upregulation in anti-fibrotic (E-cadherin) and anti-inflammatory (IL4, IL10) gene expression was significantly different in the fibrotic model treated by AEVs compared to NEVs. Also, the downregulation of fibrotic (TGF-β1, vimentin, collagen I) and pro-inflammatory (IL1, TNFα) gene expression was significantly different in AEVs compared with those treated by NEVs., Conclusion: Our findings suggest that AEVs can be considered as a therapeutic modality for renal fibrosis in the future., Competing Interests: The authors declare that there is no conflict of interests., (© 2023 The Author(s).)

Introduction: Treatment of critical-sized bone defects is challenging. Tissue engineering as a state-of-the-art method has been concerned with treating these non-self-healing bone defects. Here, we studied the potentials of new three-dimensional nanofibrous scaffolds (3DNS) with and without human adipose mesenchymal stem cells (ADSCs) for reconstructing rat critical-sized calvarial defects (CSCD). Methods: Scaffolds were made from 1- polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA) (PTFE/ PVA group), and 2- PTFE, PVA, and graphene oxide (GO) nanoparticle (PTFE/ PVA/GO group) and seeded by ADSCs and incubated in osteogenic media (OM). The expression of key osteogenic proteins including Runt-related transcription factor 2 (Runx2), collagen type Iα (COL Iα), osteocalcin (OCN), and osteonectin (ON) at days 14 and 21 of culture were evaluated by western blot and immunocytochemistry methods. Next, 40 selected rats were assigned to five groups (n=8) to create CSCD which will be filled by scaffolds or cell-containing scaffolds. The groups were denominated as the following order: Control (empty defects), PTFE/PVA (PTFE/PVA scaffolds implant), PTFE/PVA/GO (PTFE/PVA/GO scaffolds implant), PTFE/PVA/Cell group (PTFE/PVA scaffolds containing ADSCs implant), and PTFE/PVA/GO/Cell group (PTFE/PVA/GO scaffolds containing ADSCs implant). Six and 12 weeks after implantation, the animals were sacrificed and bone regeneration was evaluated using computerized tomography (CT), and hematoxylin-eosin (H&E) staining. Results: Based on the in-vitro study, expression of bone-related proteins in ADSCs seeded on PTFE/PVA/GO scaffolds were significantly higher than PTFE/PVA scaffolds and TCPS ( P <0.05). Based on the in-vivo study, bone regeneration in CSCD were filled with PTFE/PVA/GO scaffolds containing ADSCs were significantly higher than PTFE/PVA scaffolds containing ADSCs ( P <0.05). CSCD filled with cell-seeded scaffolds showed higher bone regeneration in comparison with CSCD filled with scaffolds only ( P <0.05). Conclusion: The data provided evidence showing new freeze-dried nanofibrous scaffolds formed from hydrophobic (PTFE) and hydrophilic (PVA) polymers with and without GO provide a suitable environment for ADSCs due to the expression of bone-related proteins. ADSCs and GO in the implanted scaffolds had a distinct effect on the bone regeneration process in this in-vivo study., (© 2023 The Author(s).)

A gradual degeneration of the striatum and loss of nigral dopamine cells are characteristic of Parkinson's disease. Nowadays, combination therapy for neurodegenerative disease is considered. This study aimed to investigate the effects of melatonin and dopaminergic neurons derived from adipose tissue stem cells (ADSCs) in a rat model of Parkinson's disease. Parkinson's disease was induced in rats using neurotoxin 6-Hydroxydopamine. The treatment was performed using melatonin and dopaminergic neurons transplantation. Subsequently, behavioral tests, western blot analysis for Caspase-3 expression, GSH (Glutathione) content and stereology analysis for the volume and cell number of substantia nigra and striatum were performed. Treatment with melatonin and dopaminergic neuron transplantation increased the number of neurons in substantia nigra and striatum while the number of glial cell and the volume of substantia nigra and striatum did not show significant change between groups. Western blot analysis for caspase 3 indicated the significant differences between groups. The results also indicated the increased level of glutathione (GSH) content in treatment groups. this study showed that combination therapy with melatonin and dopaminergic neurons could greatly protect the neurons, reduce oxidative stress and improve the symptoms of PD., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Recent investigations of COVID-19 have largely focused on the effects of this novel virus on the vital organs in order to efficiently assist individuals who have recovered from the disease. In the present study we used hippocampal tissue samples extracted from people who died after COVID-19. Utilizing histological techniques to analyze glial and neuronal cells we illuminated a massive degeneration of neuronal cells and changes in glial cells morphology in hippocampal samples. The results showed that in hippocampus of the studied brains there were morphological changes in pyramidal cells, an increase in apoptosis, a drop in neurogenesis, and change in spatial distribution of neurons in the pyramidal and granular layer. It was also demonstrated that COVID-19 alter the morphological characteristics and distribution of astrocyte and microglia cells. While the exact mechanism(s) by which the virus causes neuronal loss and morphology in the central nervous system (CNS) remains to be determined, it is necessary to monitor the effect of SARS-CoV-2 infection on CNS compartments like the hippocampus in future investigations. As a result of what happened in the hippocampus secondary to COVID-19, memory impairment may be a long-term neurological complication which can be a predisposing factor for neurodegenerative disorders through neuroinflammation and oxidative stress mechanisms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Many systemic and ocular diseases cause macular edema (ME). Macular edema is seen in two primary forms; the first is diffuse thickening of the macula, and the other is a macula with a distinct petaloid (cloverleaf) appearance called cystoid macular edema. Macular edema has a known role in the reduction of visual equity, and many options have been proposed for the reversal of this condition. Methods: Articles on the effects of macular laser grid photocoagulation on diabetic macular edema (DME) or cystoid macular edema published between 2000 and 2022 were collected from PubMed, Google Scholar, and Web of Science. The following keywords were used for the search: "macular laser photocoagulation", "macular edema", "cystoid macular edema", "intravitreal pharmacotherapies", and "antivascular endothelial growth factor". Two hundred nineteen articles were found in google scholar and 165 articles in PubMed, and a total of 58 articles were included in the study after applying the exclusion criteria. Results: We investigated the effects of various lasers photocoagulation such as Focal and/or grid macular laser, subthreshold micropulse laser (SMPL), as well as intravitreal pharmacotherapies with triamcinolone acetonide, and fluocinolone, and extended released intraocular implants such as Ozurdex, Retisert, Iluvien, and anti-vascular endothelial growth factors such as bevacizumab (Avastin), Eyela, and Lucentis. Corticosteroids were more effective than lasers, although some researchers have found that lasers and combined lasers and corticosteroids are more effective. In addition, some studies have shown that the frequency and concentrations of intravitreal pharmacotherapies are effective in increasing visual outcomes. Conclusion: The results of the studies showed that the combined intravitreal corticosteroids are much more effective in improving visual acuity (VA) than a single corticosteroid, and the low concentration of the drug is safer. Still, corticosteroids have side effects such as increased intraocular pressure and glaucoma. Therefore, combining the medication with a laser is much more reasonable than each alone. Also, the subthreshold photocoagulation laser (670 nm) is better at reducing the central macular thickness (CMT) and improving VA than the micro pulse yellow laser and pan-retinal photocoagulation (PRP)., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 J Lasers Med Sci.)

The current study aimed to compare the possible effects of differential learning strategy, self-controlled feedback, and external focus of attention on kinetic and kinematic risk factors of anterior cruciate ligament (ACL) injury in athletes. Forty-eight male athletes from three sports of handball, volleyball and basketball were selected for this study and were randomly divided into four groups: differential learning ( n = 12), self-control feedback ( n = 12), external focus ( n = 12), and control ( n = 12) group. All groups followed the intervention for eight weeks with three sessions per week. Data were analyzed by means of 4 × 2 repeated measures ANOVA followed by post hoc comparison (Bonferroni) at the significance level of p ≤ 0.05. A significant group × time interaction and the main effect of time was found for most kinetic and kinematic variables. The main effect of the group was significant only at the knee abduction angle. Differential learning and external focus of attention methods positively reduced the kinetic and kinematic variables that are considered risk factors for ACL injury. However, the effect sizes (Cohen's d) for the changes in most of the variables were larger for the differential learning group. Tailoring the boundary conditions that are based on the manipulations created in the exercise through variability and variety of movements associated with differential learning methods rather than repeating movements could reduce the risk of ACL injury.

Introduction: Multiple sclerosis (MS) is one of the autoimmune and chronic diseases of the central nervous system; this disease occurs more frequently in young people and women and leads to neurological symptoms. Oxidative stress, inflammatory processes, and oligodendrocyte dysfunction have a pivotal role in the pathophysiology of this disease. Nowadays it is reported that photobiomodulation (PBM) as a non-invasive treatment has neuroprotective potential, but the exact mechanisms are not understood. Methods: In this study, we reviewed the effects of PBM on MS. In this regard, we used the keywords "Photobiomodulation", "Laser therapy", and "Low-level laser therapy" on MS to find related studies on this subject in PubMed, Google scholar, Elsevier, Medline, and Scopus databases. Results: PBM has positive effects on MS by regulating the inflammatory process, controlling immune cell activity and mitochondrial functions, as well as inhibiting free radicals production which finally leads to a reduction in neurological defects and an improvement in the functional status of patients. Conclusion: Overall, researchers have suggested the use of laser therapy in neurodegenerative diseases due to its numerous therapeutic effects., Competing Interests: The authors declare that they have no conflict of interest, (Copyright © 2022 J Lasers Med Sci.)

Hearing is mainly dependent on the function of hair cells (HCs) and spiral ganglion neurons (SGNs) which damage or loss of them leads to irreversible hearing loss. Olfactory ensheathing cells (OECs) are specialized glia that forms the fascicles of the olfactory nerve by surrounding the olfactory sensory axons. The OECs, as a regenerating part of the nervous system, play a supporting function in axonal regeneration and express a wide range of growth factors. In addition, retinoic acid (RA) enhances the proliferation and differentiation of these cells into the nerve. In the present study, we co-cultured human OECs (hOECs) with cochlear SGNs in order to determine whether hOECs and RA co-treatment can protect the repair process in gentamycin-induced SGNs damage in vitro. For this purpose, cochlear cultures were prepared from P4 Wistar rats, which were randomly appointed to four groups: normal cultivated SGNs (Control), gentamicin-lesioned SGNs culture (Gent), gentamicin-lesioned SGNs culture treated with OECs (Gent + OECs) and gentamicin-lesioned SGNs culture co-treated with OECs and RA (Gent + OEC& RA). The expression of a specific protein in SGNs was examined using immunohistochemical and Western blotting technique. TUNEl staining was used to detect cell apoptosis. Here, we revealed that combined treatment of OECs and RA protect synapsin and Tuj-1 expression in the lesioned SGNs and attenuate cell apoptosis. These findings suggest that RA co-treatment can enhance efficiency of OECs in repair of SGNs damage induced by ototoxic drug., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Parkinson's disease (PD) is a progressive and severe neurodegenerative disorder of the central nervous system (CNS). The most prominent features of this disease are cell reduction in the substantia nigra and accumulation of α-synuclein, especially in the brainstem, spinal cord, and cortical areas. In addition to drug-based treatment, other therapies such as surgery, cell therapy, and laser therapy can be considered. In this study, articles on cell therapy and laser therapy for PD have been collected to evaluate the improvement of motor function, cell differentiation, and dopaminergic cell proliferation. Methods: Articles were collected from four electronic databases: PubMed, Scopus, Google Scholar, and Web of Science from 2010 to 2022. The keywords were "photobiomodulation", "low-level light therapy", "Low-level laser therapy", "near-infrared light", "Parkinson's disease", "Parkinsonism", and "stem cell therapy". About 100 related articles were included in the study. Results: The results of the studies showed that cell therapy and laser therapy are useful in the treatment of PD, and despite their limitations, they can be useful in improving PD. Conclusion: Concomitant use of cell therapy and photobiomodulation therapy can improve the symptoms of PD., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 J Lasers Med Sci.)

Abstract: Ghanati, HA, Letafatkar, A, Almonroeder, TG, and Rabiei, P. Examining the influence of attentional focus on the effects of a neuromuscular training program in male athletes. J Strength Cond Res 36(6): 1568-1575, 2022-Neuromuscular training programs that incorporate lower extremity strengthening, plyometric exercises, balance training, and movement retraining are recommended for anterior cruciate ligament injury prevention; however, there is a need to improve their effectiveness. The purpose of this study was to examine how athletes' attentional focus during training influences the effects of an 8-week neuromuscular training program on hip strength, single-leg landing mechanics, and hop performance. Sixty-six male athletes were randomly allocated to a group that trained with an internal focus, a group that trained with an external focus, or a control group. All athletes completed testing before (baseline) and after (posttesting) the 8-week period. Isokinetic hip strength, hip and knee kinematics and ground reaction forces during landing, and hop distance were examined as part of this study. Analysis of covariance was used to compare posttesting outcomes among the groups while accounting for group differences in baseline performance. The neuromuscular training program resulted in improved hip abduction strength, reduced hip adduction and internal rotation motion during landing, and increased hop distance for athletes who trained with an external focus. However, the program did not seem to influence hip strength, landing kinematics, or hop performance for athletes who trained with an internal focus. Our findings indicate that male athletes may benefit from completing a neuromuscular training program with an external focus vs. an internal focus. Trainers, coaches, and clinicians should consider using instructions that promote an external focus when implementing neuromuscular training programs with male athletes., (Copyright © 2020 National Strength and Conditioning Association.)

Busulfan (BSU) is a chemotherapeutic drug that can cause subfertility or sterility in males. We investigated the effects of adipose tissue-derived mesenchymal stem cells (AT-MSC) conditioned medium (CM) (AT-MSC-CM) on histopathological and molecular characteristics of mouse testes exposed to BSU using stereology. We used adult male mice divided randomly into five groups: control, Dulbecco's modified Eagle's medium (DMEM), dimethyl sulfoxide (DMSO), BSU, and BSU + CM. Thirty-five days following BSU injection, sperm and testis tissues were harvested for stereological and molecular studies. The BSU group exhibited significantly reduced testis volume, interstitium and tubules compared to the other groups, although the volume of the testis remained unchanged for BSU and CM groups. The number of testis cells was reduced in the BSU group compared to the other groups. The CM group exhibited a significantly increased number of testis cells compared to the BSU group. Sperm count and motility, and length density of seminiferous tubules were increased in CM group compared to the BSU group. AT-MSC-CM exhibited ameliorative effects on histopathologic changes of mouse testes exposed to BSU.

Background: Using neural stem cells (NSCs) in cell therapy and regenerative medicine is a growing knowledge. In this study, the protective role of carnosic acid and trehalose against H2O2-induced oxidative stress in autophagy induction and apoptosis inhibition in NSCs was investigated., Material and Methods: The bone marrow stromal cells (BMSCs) were isolated from the femur of the rat and differentiated into NSCs using basic fibroblast and epidermal growth factors (bFGF and EGF), and B27 serum free media. To evaluate the autophagy, the P62 protein was assessed by immunocytochemistry and LC3II / LC3I ratio by Western blotting. Further, we used 3-Methyladenine (3-MA), a widely used autophagy inhibitor to study whether combined treatment of 3-MA with carnosic acid and trehalose modulates autophagy in NSCs. For studying apoptosis, the cleaved caspase-3 protein was evaluated. Carnosic acid and trehalose increased the survival of the NSCs., Results: The H2O2 decreased the autophagy and induced apoptosis with increasing time during 24 hours, however, a pre-treatment with 2 μM carnosic acid and trehalose 3 % induced the autophagy proteins (while increasing the LC3II / LC3I ratio and decreasing the P62) and decreased the apoptosis (while decreasing the expression of the cleaved caspase-3). The results showed that the carnosic acid and trehalose increased the survival of NSCs against the oxidative stress caused by H2O2, decreased apoptosis, and induced autophagy., Conclusion: Due to the carnosic acid and trehalose unique properties and its low toxicity, it can be used as an agent in cellular transplantation for reducing oxidative stress and inducing autophagy (Fig. 4, Ref. 37).

Following severe Spinal Cord Injury (SCI), regeneration is inadequate, and functional recovery is incomplete. The occurrence of oxidative stress and the spread of inflammation play a crucial role in the failure to regenerate the injury site. In this way, we explored the neuroprotective effects of PhotoBioModulation (PBM), as the main factor in controlling these two destructive factors, on SCI. fifty-four female adult Wistar rats divided into three groups: sham group (just eliminate vertebra lamina, n = 18), SCI group (n = 18), and SCI-PBM group which exposed to PBM (150 MW, 50 min/day, 14 days, n = 18). After SCI induction at the endpoint of the study (the end of 8 week), we took tissue samples from the spinal cord for evaluating the biochemical profiles that include Catalase (CAT), Malondialdehyde (MDA), Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-PX) levels, immunohistochemistry for Caspase-3, gene expressions of Interleukin-1β (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), and Interleukin (IL-10). Also, stereological assessments evaluated the spinal cord, central cavity volumes, and numerical density of the glial and neural cells in the traumatic area. The open-field test, rotarod test, Narrow Beam Test (NBT), Electromyography recording (EMG) test and the Basso-Beattie-Bresnehan (BBB) evaluated the neurological functions. Our results showed that the stereological parameters, biochemical profiles (except MDA), and neurological functions were markedly greater in the SCI-PBM group in comparison with SCI group. The transcript for the IL-10 gene was seriously upregulated in the SCI-PBM group compared to the SCI group. This is while gene expression of TNF-α and IL-1β, also density of apoptosis cells in Caspase-3 evaluation decreased significantly more in the SCI-PBM group compared to the SCI group. Overall, using PBM treatment immediately after SCI has neuroprotective effects by controlling oxidative stress and inflammation and preventing the spread of damage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nowadays, mesenchymal stem cells (MSCs) are the most widely used cell sources for bone regenerative medicine. Electrospun polyacrylonitrile (PAN)-based scaffolds play an important role in bone tissue engineering due to their good mechanical properties, which could be enhanced by the presence of nanoparticles such as nanoclay. This study evaluated the in-vitro effect of different concentrations of nanoclay in surface characteristic properties of PAN-based electrospun nanofiber scaffolds and the osteogenic differentiation ability of adipose-derived mesenchymal stem cells (AD-MSCs). After electrospinning nanofibers, their structure were assessed through some characterization tests. Then AD-MSCs isolation and characterization were done, and the cell attachment and the biocompatibility were determined. Finally, osteogenic differentiation-related markers, genes, and proteins were studied. Clay-PAN25% electrospun nanofiber scaffold could support attachment, proliferation, and osteogenic differentiation of AD-MSCs better than other groups. Also, nanoclay could enhance the properties of PAN-based scaffolds, such as fiber diameter, topography, surface charge, hydrophilicity, roughness, and degradation, as well as osteogenic differentiation of cells. As a result, Clay-PAN25% with the highest concentration of nanoclay was found as a promising biodegradable and cost-effective scaffold for osteogenic differentiation of AD-MSCs.

To evaluate the incidence of apoptosis within the testes of patients who died from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications, testis tissue was collected from autopsies of COVID-19 positive (n = 6) and negative men (n = 6). They were then taken for histopathological experiments, and RNA extraction, to examine the expression of angiotensin-converting enzyme 2 (ACE2), transmembrane protease, serine 2 (TMPRSS2), BAX, BCL2 and Caspase3 genes. Reactive oxygen species (ROS) production and glutathione disulfide (GSH) activity were also thoroughly examined. Autopsied testicular specimens of COVID-19 showed that COVID-19 infection significantly decreased the seminiferous tubule length, interstitial tissue and seminiferous tubule volume, as well as the number of testicular cells. An analysis of the results showed that the Johnsen expressed a reduction in the COVID-19 group when compared to the control group. Our data showed that the expression of ACE2, BAX and Caspase3 were remarkably increased as well as a decrease in the expression of BCL2 in COVID-19 cases. Although, no significant difference was found for TMPRSS2. Furthermore, the results signified an increase in the formation of ROS and suppression of the GSH activity as oxidative stress biomarkers. The results of immunohistochemistry and TUNEL assay showed that the expression of ACE2 and the number of apoptotic cells significantly increased in the COVID-19 group. Overall, this study suggests that COVID-19 infection causes spermatogenesis disruption, probably through the oxidative stress pathway and subsequently induces apoptosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Methamphetamine (Meth) is a neuro-stimulator substrate which might lead to neural cell death and the activation of several interconnected cellular pathways as well. However, the precise molecular mechanisms underlying Meth-induced neural cell death remained unclear yet. The current study aimed to assess the specific relationship between long-term Meth exposure and several endoplasmic reticulum stress, autophagy, and apoptosis associated markers including C/EBP homologous protein (CHOP), Tribbles homolog 3(Trib3), Nuclear protein 1(NUPR1), and Beclin-1 expression in postmortem human striatum. Therefore, the effects of long-term Meth exposure on autophagy and apoptosis in the striatum of postmortem users were evaluated and molecular, immunehistochemical, and histological examinations were performed on 10 control and 10 Meth-addicted brains. The level of CHOP, Trib3, NUPR1, and Beclin-1, Microtubule-associated proteins 1A/1B light chain 3B(LC3), Caspase 3, and Autophagy protein 5 (ATG5) were measured by using qPCR and immunohistochemistry. Stereological neural cell counting, Hematoxylin and Eosin, Nissl and Tunel staining were also performed. Based on our findings, the expression level of CHOP, Trib3, NUPR1, and Beclin-1 in the striatum of Meth group were significantly higher than the control group. Besides, the neuronal cell death was substantially increased in the striatum based on data obtained from the Tunel assay and the stereological analysis. Long-term presence of Meth in the brain can induce ER stress and overexpression of NUPR1 which is associated with the upregulation of CHOP, a pro-apoptotic transcription factor. Moreover, an increase in Trib3 expression is implicated in CHOP-dependent autophagic cell death during Meth-induced ER stress accompanied by an increase in neuronal cell death in the striatum of the postmortem human brains. Beclin 1 expression was also upregulated which may due to the activation of autophagic mechanisms upon prolonged Meth exposure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Noise-induced hearing loss (NIHL) is the second most common cause of acquired hearing loss. Acoustic trauma can cause oxidative damage in the cochlear hair cells (HCs) through apoptotic pathways. Apelin is a newly discovered neuropeptide with neuroprotective effects against the oxidative stress in neurodegenerative disorder. We investigated the preventive effects of apelin-13 on the cochlear HCs and spiral ganglion neurons (SGNs) against acoustic trauma via Sirtuin-1 (Sirt-1) regulation in rats. Animals were assigned to control, control + apelin-13 (50 or 100 μg/kg, ip), and noise exposure groups without any treatment or were administered apelin-13 (50 or 100 μg/kg, ip) and EX-527 (an inhibitor of Sirt-1) prior to each noise session. In the noise groups, 110 dB white noise was applied for 6 h per 5 days. Pre- and post-exposure distortion product otoacoustic emissions (DPOAE) and cochlear superoxide dismutase (SOD) activity were assessed. Western blot evaluated the cochlear protein expressions of Sirt-1, cleaved-caspase-3, Bax, and Bcl-2. Cell apoptosis was detected through TUNEL staining. Immunofluorescence was used to examine expression of HCs and SGNs specific protein. DPOAE level were significantly improved in the noise exposure group receiving 100 μg/kg apelin-13. At high doses, apelin augmented SOD levels in the rat cochlea subjected to noise. Apelin 100 markedly increased Sirt-1, and decreased cleaved- caspase-3 expression as well as Bax/Bcl-2 ratio in the cochlea tissue of noise-exposed rats. These findings suggest the promising therapeutic potential of apelin-13 for the prevention of noise-induced injury to cochlea and hearing loss., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The recent coronavirus disease of 2019 (COVID-19) pandemic has adversely affected people worldwide. A growing body of literature suggests the neurological complications and manifestations in response to COVID-19 infection. Herein, we explored the inflammatory and immune responses in the post-mortem cerebral cortex of patients with severe COVID-19. The participants comprised three patients diagnosed with severe COVID-19 from March 26, 2020, to April 17, 2020, and three control patients. Our findings demonstrated a surge in the number of reactive astrocytes and activated microglia, as well as low levels of glutathione along with the upregulation of inflammation- and immune-related genes IL1B, IL6, IFITM, MX1, and OAS2 in the COVID-19 group. Overall, the data imply that oxidative stress may invoke a glial-mediated neuroinflammation, which ultimately leads to neuronal cell death in the cerebral cortex of COVID-19 patients.

Objective: In vitro maturation (IVM) of human oocytes is used to induce meiosis progression in immature retrieved oocytes. Calcium (Ca 2+ ) has a central role in oocyte physiology. Passage through meiosis phase to another phase is controlled by increasing intracellular Ca 2+ . Therefore, the current research was conducted to evaluate the role of calcium ionophore (CI) on human oocyte IVM., Materials and Methods: In this clinical trial study, immature human oocytes were obtained from 216 intracytoplasmic sperm injection (ICSI) cycles. After ovarian stimulation, germinal vesicle (GV) stage oocytes were collected and categorized into two groups: with and without 10 μM CI treatment. Next, oocyte nuclear maturation was assessed after 24-28 hours of culture. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess the transcript profile of several oocyte maturation-related genes ( MAPK3, CCNB1, CDK1, and cyclin D1 [CCND1] ) and apoptotic-related genes ( BCL-2, BAX , and Caspase-3 ). Oocyte glutathione (GSH) and reactive oxygen species (ROS) levels were assessed using Cell Tracker Blue and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent dye staining. Oocyte spindle configuration and chromosome alignment were analysed by immunocytochemistry., Results: The metaphase II (MII) oocyte rate was higher in CI-treated oocytes (73.53%) compared to the control (67.43%) group, but this difference was not statistically significant (P=0.13). The mRNA expression profile of oocyte maturation-related genes ( MAPK3, CCNB1, CDK1, and CCND1 ) (P<0.05) and the anti-apoptotic BCL-2 gene was remarkably up-regulated after treatment with CI (P=0.001). The pro-apoptotic BAX and Caspase-3 relative expression levels did not change significantly. The CI-treated oocyte cytoplasm had significantly higher GSH and lower ROS (P<0.05). There was no statistically significant difference in meiotic spindle assembly and chromosome alignment between CI treatment and the control group oocytes., Conclusion: The finding of the current study supports the role of CI in meiosis resumption of human oocytes. (Registration Number: IRCT20140707018381N4)., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Spinal cord injury (SCI) can cause various symptoms, including pain, complete or incomplete loss of autonomic, sensory, motor and functions inferior to the site of the damage. Despite wondrous advances in medicine, treating spinal cord injuries remains a thorny issue yet. Recently, the control of inflammatory processes after damage to the nervous system has been noticed as a promising therapeutic target. The goal of the present experiment was to identify the effects of apelin-13 on the histological outcome, inflammatory factors, and functional recovery in the animal contusion model of SCI were analyzed. 40 Female Wistar rats were randomly but equally assigned in laminectomy, contusion, PBS (1 mL PBS, i.p), control group which received apelin-13 (control + apelin, 100 μg/kg, i.p), and apelin-13 treatment groups. In the treatment group, apelin-13 (100 μg/kg) was injected intraperitoneally 30 min after injury. The weight-dropping contusion model was used for inducing SCI. The Basso, Beattie, and Bresnahan scale (BBB), narrow beam test (NBT), rotarod test, and the open-field test was applied to evaluate locomotor and behavioral activity. Real-time polymerase chain reaction (PCR) and ELISA technique was accomplished eight weeks after inducing SCI to measure the level of fibroblast growth factor FGF-1, FGFR1 and the inflammatory factors including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, and IL-10. Furthermore, histological change was estimated by H&E staining. Our results showed that apelin-13 treatment after SCI led to a significant increase in functional recovery and behavioral tests. Stereological estimation illustrated that apelin-13 could reduce significantly central cavity volume and number of glial cells, and also increase significantly spinal cord volume and number of neural cells. PCR and ELISA evaluation shows a significant increase in IL-10 level and decrease in levels of FGF-1, FGF-R1, and pro-inflammatory cytokines (PIC). This study suggested that apelin-13 has neuroprotective effects by regulating the inflammatory process after SCI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Spermatogenesis process is sensitive to heat stress because the testicular temperature is 2 to 4 °C lower than the core body temperature. The current study aimed to investigate the effects of iron oxide nanoparticles containing curcumin on spermatogenesis in mice induced by long-term scrotal hyperthermia. In this experimental study, 18 mice were equally divided into the following three groups: control, scrotal hyperthermia, and scrotal hyperthermia + curcumin-loaded iron particles (NPs) (240 μL) (mice were treated for 20 days). Hyperthermia was induced by exposure to the temperature of 43 °C for 20 min every other day for 5 weeks. Afterward, the animals were euthanized; sperm samples were collected for sperm parameters analysis, and testis samples were taken for histopathology experiments, evaluation of serum testosterone level, and RNA extraction in order to examine the expression of c-kit, STRA8 and PCNA genes. Our study showed that curcumin-loaded iron particles could notably increase the volume of testis, length of seminiferous tubules, sperm parameters, and stereological parameters (i.e., spermatogonia, primary spermatocyte, round spermatid, and Leydig cells) thereby increasing serum testosterone level; in addition, TUNEL-positive cells showed a significant decrease in curcumin-loaded iron particle group. Thus, based on the obtained results, the expression of c-kit, STRA8, and PCNA genes was significantly increased in treatment groups by curcumin-loaded iron particles compared with scrotal hyperthermia-induced mice. In conclusion, curcumin-loaded iron particles can be considered an alternative treatment for improving the spermatogenesis process in scrotal hyperthermia-induced mice.

Objectives: The present study was aimed to investigate the therapeutic effect of mesenchymal Stem Cell Therapy in the left ventricular ejection fraction (LVEF), left ventricular enddiastolic volume (LVEDV), and  left ventricular endsystolic volume (LVESV) after myocardial infarction (MI)., Background: Previous investigations propose that stem cell therapy may help treat myocardial infarction (MI). However, there are controversial data from different studies., Methods: We studied the relevant scientific literature available up to 2020. Comprehensive Meta-Analysis Software (CMAS) Version 2.0 were used for statistical analyses. Fixed or random-effect model was used to identify the weighted mean difference (WMD) with 95% confidence intervals (CI). The statistically significant level used for interpreting publication bias was less than 0.05., Results: We identified 30 studies that met the inclusion criteria. In the overall pooled estimate, cell therapy had an effect on the LVEF change from baseline to follow-up (WMD: 2.98 mL, 95% CI: 1.66 to 4.29). The pooled WMD was found to be -4.16 (95% CI: -7.91 to -0.40) and -5.62 (95% CI: -9.20 to -2.00), for LVEDV, and LVESV, respectively. Thus, reduction in LVEDV and LVESV were significant in the treatment group participants., Conclusions: The present systematic review indicated that cell therapy in patients, who have MI could be effective and applicable clinically (Tab. 3, Fig. 7, Ref. 48). Text in PDF www.elis.sk Keywords: myocardial infarction, stem cell, systematic review, randomized clinical trials.

Background: ADHD is the most common developmental disorder affecting approximately three to seven percent of school-aged children and 2.5 percent of adults worldwide. The drug of choice for the pharmacotherapy of ADHD is Methylphenidate (MPH). However, there is growing concerns about side effects resulting from its potential interference with brain anatomical and behavioral development., Aim: This article focuses on the adverse effects of MPH on the rat's hippocampus., Methods: The animals received an oral dose of 5 mg/kg MPH or normal saline, as the vehicle, on a daily basis for 30 days. Y-maze test, passive avoidance, Barnes maze and field potential recording were conducted. Western blot for detecting the neurotrophic factor of GDNF and immunohistochemistry of astrogliosis were performed., Results: Our results revealed that MPH treatment suppressed the willingness of rats to explore new environments. Also, it had no effect on improving long-term potentiation, long-term memory and spatial memory in the MPH group as opposed to the control group. There was also a significant increase of astrogliosis in the treated rats' hippocampi. On the other hand, there was not a significant relationship between MPH administration and the decrement of the GDNF level., Conclusion: We encourage the need to conduct more research on the adverse effects of MPH on the brain., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)