Dexmedetomidine, an alpha-2 adrenoceptors agonist, provides a neuroprotective effect for dopaminergic neurons in the substantia nigra and attenuates glucose imbalance in the 6-hydroxydopamine animal model of Parkinson's disease.

INTRODUCTION: Studies have shown that dexmedetomidine (DEX, an a2-adrenoceptors agonist) provides a neuroprotective effect and influences blood glucose levels. Here, we evaluated the effect of prolonged treatment with low doses of DEX on the survival rate of dopaminergic (DAergic) neurons in the substantia nigra and also serum glucose levels in 6-hydroxydopamine (6-OHDA) - induced Parkinson's disease (PD) in the rat. MATERIAL AND METHODS: The neurotoxin of 6-OHDA was injected into the medial forebrain bundle by stereotaxic surgery. DEX (25 and 50 µg/kg, i.p) and yohimbine, an a2-adrenoceptor antagonist (1 mg/kg, i.p) were administered before the surgery to the 13 weeks afterward. Apomorphine-induced rotational tests and blood sampling were carried out before the surgery and multiple weeks after that. Thirteen weeks after the surgery, the rats' brain was transcardially perfused to assess the survival rate of DAergic neurons using the tyrosine hydroxylase (TH) immunohistochemistry. RESULTS: DEX remarkably attenuated the severity of rotational behavior and reversed the progress of the PD. It also increased the number of TH-labeled neurons by up to 60%. The serum glucose levels in 6-OHDA-received rats did not change in the third and seventh weeks after the surgery but decreased significantly in the thirteenth week. Treatment with DEX prevented this decrement in glucose levels. On the other hand, Treatment with yohimbine did not affect PD symptoms and glucose levels. CONCLUSION: Our data indicate that DEX through neuroprotective activity attenuates the severity of 6-OHDA-induced PD in rats. DEX might also prevent hypoglycemia during the progress of the PD.

Therapeutic Effects of Exosome Therapy and Photobiomodulation Therapy on the Spermatogenesis Arrest in Male Mice After Scrotum Hyperthermia.

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.

Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease.

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.

Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure. METHODS: PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama. RESULTS: A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression. CONCLUSION: Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.

All-trans retinoic acid and fibroblast growth factor-2 enhance the fertility rate and embryo development in polycystic ovary syndrome mouse model.

Objectives: Polycystic ovary syndrome (PCOS) causes a developmental arrest of antral follicles and disrupts oocyte maturation. Retinoic acid (RA) and Fibroblast Growth Factor-2 (FGF2) are effective in follicle growth, thus their effects on histopathology and in vitro fertility of oocytes were investigated in PCOS-induced mice. Materials and Methods: Eighty female NMRI mice were randomly divided into 8 groups including 1-Normal mice, 2-PCOS mice without any treatment, 3-Normal mice treated with RA, 4-Normal mice treated with FGF2, 5-PCOS mice treated with RA, 6- PCOS mice treated with FGF2, 7- PCOS mice treated with RA and FGF2, and 8- Normal mice treated with RA and FGF2. Following PCOS induction, the mice were treated with intraperitoneal RA and FGF2 as a treatment. Then ovarian stimulation, for preparing the oocyte and embryo microscopic examinations was performed. After oocyte morphometry, through in vitro fertilization, the embryo formation was assessed. Data was analyzed by one-way ANOVA and Tukey tests. Results: The results showed simultaneous injection of RA and FGF2 into PCOS-induced mice increases antral follicles and corpus luteum, but decreases cystic follicles. Simultaneous injection of these two substances into healthy mice increases the pre-antral follicles and corpus luteum. Simultaneous injection of RA and FGF2 increases the number of embryos in both control and intervention groups. Conclusion: It can be concluded that RA and FGF2 increase the maturity of ovarian follicles, the number of two-celled embryos, and the number of grade-A embryos in mice with PCOS, which is more effective when these two substances are injected simultaneously.

Great potential of renal progenitor cells in kidney: From the development to clinic.

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.

Exploring amygdala structural changes and signaling pathways in postmortem brains: consequences of long-term methamphetamine addiction.

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.

Unveiling Therapeutic Potential: A Systematic Review of Photobiomodulation Therapy and Biological Dressings for Diabetic Foot Ulcers.

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.

Molecular mechanisms and treatment strategies for methamphetamine­induced neurodegeneration, inflammation and neurotoxicity.

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 METH­induced 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 blood­brain barrier is compromised, leading to structural, functional, and neurochemical alterations, particularly in the fronto­striatal 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 METH­induced neurotoxicity and develop effective treatment approaches.

Low-Level Laser and Bovine Amniotic Fluid-derived Cream Accelerating Skin Neck Wound Healing and Reducing Inflammation and Wound Scar in a Rat Animal Model.

Background: Nowadays, wound healing is one of the main problems of patients. Therefore, extensive research is underway to discover mechanisms associated with non-scarring of wounds. Using amniotic fluid and laser may potentially play a key role in wound healing and scar reduction due to its presence in tissue growth and repair agents. Aim: The present study evaluated the effect of bovine amniotic fluid (BAF)-derived cream and low-power laser (LPL) on accelerating skin wound healing and reducing scarring in an animal model. Materials and Methods: Therefore, 72 male Wistar rats were randomly divided into three groups (each group: 24). A wound 6 mm in diameter was then inflicted on the rats' backs. In the first group that was the control group, the wound was only used. Moreover, BAF was implemented for the second group, and in the third group, LPL radiation was utilized. On the 1st, 3rd, 5th, 14th, and 21st days, the healing condition of the wound and scar created were examined. Results: Hence, evaluation of wound healing status on days 5 and 14 showed that the wound healing scale in the BAF group and LPL group was significantly better than that of the control group. On the 21st day, the average Scar Scoring Scale in the BAF and LPL groups was significantly lower than that of the control group. Histological images showed a significant repair in the LPL and BAF groups. Conclusion: To conclude, considering the positive effect of LPL and BAF on wound healing and less scarring, it seems that LPL and BAF can heal wounds faster. Moreover, they can be used to prevent scarring after wound healing.

Trehalose and carnosic acid induced LC3I, LC3II ratio, P62 down-regulation and cleaved caspase 3 expression in neural stem cells.

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).

Silk fibroin and Nettle extract promote wound healing in a rat model: A histological and morphometrical study.

INTRODUCTION: Considering the anti-inflammatory, antimicrobial ability, and antioxidant effects besides stimulating ability of silk fibroin (SF) in cell migration and proliferation of Nettle, the current study aimed to investigate the effect of Nettle leaf extract (NLE) and SF on histology, morphometrical parameters and apoptosis on the wound in the rat model. MATERIALS AND METHODS: Wistar rats are divided into 5 groups, including 1-control (rats with healthy skin and no treatment); 2-wound (without any treatment); 3-SF (administration of silk fibroin solution for 14 consecutive days); 4- Nettle (administration of Nettle ointment for 14 consecutive days), and 5- Eucerin group (administration of Eucerin substance for 14 consecutive days) and then assessed wound area by photography, angiogenesis, inflammation, and thickness of epidermis using hematoxylin and eosin (H&E) staining, collagen deposition, and structure of dermis layers evaluated by Masson's trichrome staining and the apoptosis index determined by tunnel assay on days 7, 14 and 21. RESULTS: photographic illustrations showed that the wound surface environment on the seventh day in group 4 was significantly different from group 2 (p < 0.002). The rate of wound healing on the fourteenth day was higher in groups 3 and 4 than in group 2 (p < 0.001). Also, at this time, group 4 was significantly different from group 3 and group 5 (p = 0.003 and p = 0.000, respectively). There was a significant difference in epidermal thickness between the wound group and other experimental groups (p < 0.05). The number of apoptotic cells at the wound edges on the seventh day in both group 3 and group 4 had a significant decrease compared to other groups of wounds (p = 0.000), but there was a significant increase on the fourteenth day. Also, on the 21st day, a significant decrease in apoptotic cells was observed in both group 3 and group 4 compared to other wound groups (p = 0.000). DISCUSSION AND CONCLUSION: Nettle and SF maintain cell homeostasis and accelerate wound closure by reducing cell apoptosis and enhancing cell proliferation on the seventh day, but by increasing the apoptosis of fibroblast cells on the fourteenth day, they lead to remodeling and keratinocytes migration to epidermis formation. Increased apoptosis also seems to be one of the pathophysiological mechanisms to prevent the formation of keloid and hypertrophic scar tissue. SF and Nettle extract, by increasing cell proliferation and migration of different cell types to the site of injury, control the remodeling process by inducing and regulating apoptosis in the first two weeks of wound healing and accelerating the process of collagen deposition and epithelialization.

The Effect of bisphenol A and Photobiomodulation Therapy on Autophagy-Related Genes Induction in Adipose Tissue-Derived Stem Cells.

Introduction: As adipose tissue-derived stem cells (ADSCs) can divide rapidly and be prepared non-invasively, they have extensively been used in regenerative medicine. On the other hand, a new method of therapy, known as photobiomodulation (PHT), has been used to treat many diseases, such as inflammatory conditions, wound healing and pain. Besides, exposure to chemical substances such as bisphenol A (BPA), at low levels, can lead to autophagy. This study investigated the effects of BPA and PHT on the expression of autophagy-related genes, including LC3, NRF2, P62, in rat ADSCs as a model. Methods: ADSCs isolation and purification were confirmed by immunocytochemistry (ICC). The cells were then treated with different concentrations of BPA and also subjected to PHT. Reverse transcription polymerase chain reaction (RT-PCR) was used for the evaluation of LC3, NRF2 and P62 gene expressions. Oil red O staining was used for adipogenic vacuole formation. Result: ICC showed that the isolated cells were CD 49-positive but CD 31 and CD 34-negative. The viability test indicated that the number of live cells after 24 hours in the BPA groups at concentrations of 0, 1, 50, 100 and 200 µM was 100%, 93%, 81%, 72%, and 43% respectively. The difference in cell viability between groups 50, 100 and 200 µM was significant as compared with the control groups (P < 0.05). Moreover, in the group with 1 µM concentration of BPA, the expressions of LC3, NRF2 and P62 genes were upregulated. However, in the treatment group at the concentration of 200 µM of BPA, the LC3 gene was expressed, but NRF2 and P62 genes were downregulated. Conclusion: BPA and PHT induce autophagy and adiposeness in ADSCs in a dose-dependent manner.

Effects of Placenta-Derived Human Amniotic Epithelial Cells on the Wound Healing Process and TGF-ß Induced Scar Formation in Murine Ischemic-Reperfusion Injury Model.

BACKGROUND: Pressure ulcers (PUs), a result of ischemic reperfusion (IR) injuries, are prevalent skin problems which show refractoriness against standard therapeutic approaches. Besides, scar formation is a critical complication of ulcers that affects functionality and the skin's cosmetic aspect. The current study aimed to investigate the effects of placenta-derived human amniotic epithelial cells (hAECs), as important agents of regenerative medicine and stem cell therapy, on accelerating the healing of IR ulcers in mice. We also evaluated the effects of these cells on reducing the TGFß-induced scar formation. METHODS: Male Balb/c mice at the age of 6-8 weeks were subjected to three IR cycles. Afterward, the mice were divided into three experimental groups (n = 6 per group), including the control group, vehicle group, and hAECs treatment group. Mice of the treatment group received 100 µL of fresh hAECs 1 × 106 cell/ml suspension in PBS. Afterward, mice were assessed by histological, stereological, molecular, and western blotting techniques at 3, 7, 14, and 21 days after wounding. RESULTS: The histological and stereological results showed the most diminutive scar formation and better healing in the hAECs treated group compared to control group. Furthermore, our results demonstrated that the expression level of Col1A1 on days 3, 14, and 21 in the hAECs treated group was significantly lower than control. Additionally, injection of hAECs significantly reduced the expression level of Col3A1 on days 3, 7, and 21 while increased Col3A1 on the day 14. Otherwise, in the hAECs treated group, the expression levels of VEGFA on days 7 and 14 were higher, which showed that hAECs could promote angiogenesis and wound healing. Also, cell therapy significantly lowered the protein levels of TGF-ß1 on day 14, while the protein level of TGF-ß3 on day 14 was significantly higher. This data could demonstrate the role of hAECs in scar reduction in IR wounds. CONCLUSION: These results suggest that hAECs can promote re-epithelialization and wound closure in an animal model of PU. They also reduced scar formation during wound healing by reducing the expression of TGF-ß1/ TGF-ß3 ratio.

Severe Acute Respiratory Syndrome Coronavirus 2 Induces Hepatocyte Cell Death, Active Autophagosome Formation and Caspase 3 Up-Regulation in Postmortem Cases: Stereological and Molecular Study.

This research investigated the histopathological changes in the tissue of the lung, heart and liver, hepatocyte cell death, autophagy, and the apoptosis inductions in the postmortem cases. Since December 2019, coronavirus disease 2019 (COVID-19) has become a significant global health concern. In order to clarify the changes in tissues of the lung, heart and liver by COVID-19, samples were taken from five patients who died of COVID-19 and five control cases, and the pathological changes in the lung, liver, and heart tissue were studied by X-ray, computed tomography, histological studies, and stereological analysis. The formation of hyaline membranes, alveolar wall edema, and fibrin exudate was seen on histological analysis of the lungs in the COVID-19 group. Stereological analysis illustrated the number of hepatocytes, volume of the sinusoid, and volume of the liver have been decreased, however the pathological changes in the heart tissue were not observed. Serum levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and angiotensin-converting enzyme significantly increased. Real-time PCR results showed that the Bcl2, Caspase3, ATG5, and LC3 decreased while the Bax increased. COVID-19 causes fibrotic changes in the lung tissue and hepatocyte mortality in the liver tissue. Besides, it elevates the level of apoptosis and autophagy markers.

Therapeutic Effects of Photobiomodulation Therapy on Multiple Sclerosis by Regulating the Inflammatory Process and Controlling Immune Cell Activity: A Novel Promising Treatment Target.

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.

Therapeutic Effects of Combination Therapy and Photobiomodulation Therapy on Retinal Regeneration.

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).

Corrigendum to: Association between ABCC8 Ala1369Ser Polymorphism (rs757110 T/G) and Type 2 Diabetes Risk in an Iranian Population: A Case-Control Study.

Due to oversight on the part of the authors, the names of two of the co-authors have been incorrectly published in the article entitled, "Association between ABCC8 Ala1369Ser Polymorphism (rs757110 T/G) and Type 2 Diabetes Risk in an Iranian Population: A Case-Control Study", 2021, Vol. 21, No. 3, pp. 441-447 [1]. The original article can be found online at: https://doi.org/10.2174/1871530320666200713091827. Original: Amin Bakhtiyari, Karimeh Haghani, Salar Bakhtiyari*, Mohammad A. Zaimy, Nooriali Zahed, Ali Gheysarzadeh, Shahram Darabi, Seidali Nahalkhani, Mansour Amraei and Iraj Alipourfard Corrected: Amin Bakhtiyari, Karimeh Haghani, Salar Bakhtiyari*, Mohammad A. Zaimy, Ali Noori-Zadeh, Ali Gheysarzadeh, Shahram Darabi, Ali Seidkhani-Nahal, Mansour Amraei and Iraj Alipourfard.

Sex and Age Determination by Measurement of Foramen Magnum Dimensions on Computer Tomography Scanning Study in the Iranian Population.

BACKGROUND: Individual distinguishing evidence may be an imperative field of measurable investigation which demonstrates higher correct expectation rates. This process of recognizable Evidence is facilitated by the assurance of sex and age. In circumstances where there are fragmented and mangled skeletal remains, sex assurance is moderately troublesome, and it becomes important to set up the precision of cadaver bones. Therefore, this study aims to evaluate sexual dimorphism and age determination by measuring foramen magnum (FM) dimensions in the Iranian population using digital computed tomography scan. METHODS: The study sample consisted of a modern adult Iranian population of 120 males and 109 females (age range: 15-50 years). Length, width, and area of FM, also FM index were measured on base skull computed tomography scan. RESULT: All of the parameters of FM (length, width, area, and FM index), were larger in men than women. The accuracy of sex determination was up to 50.2. The highest accuracy for sex determination was FM width (67.9). This study also helps craniofacial surgeon for exact reference value of FM, which are authorize neurosurgeons' accessibility to the brain stem approach and FM region with minimum retraction. CONCLUSIONS: It can be concluded from the result, that morphometric analyze of FM is useful for sex determination but cannot be suitable for age determination.

Association between ABCC8 Ala1369Ser Polymorphism (rs757110 T/G) and Type 2 Diabetes Risk in an Iranian Population: A Case-Control Study.

OBJECTIVE: Glucose metabolism increases ATP/ADP ratio within the ß-cells and causes ATP-sensitive K+ (KATP) channel closure and consequently insulin secretion. The enhanced activity of the channel may be a mechanism contributing to the reduced first-phase of insulin secretion observed in T2DM. There is no study to date in the Kurdish ethnic group regarding the relationship between SNP Ala1369Ser (rs757110 T/G) of SUR1 gene and T2DM, and additionally, the results of this association in other populations are inconsistent. Therefore, our aim in this study was to explore the possible association between SNP Ala1369Ser and type 2 diabetes in an Iranian Kurdish ethnic group. METHODS: In this study, we checked out the frequency of alleles and genotypes of SNP Ala1369Ser in T2DM individuals (207 patients; men/women: 106/101) and non-T2DM subjects (201 controls; men/women: 97/104), and their effects on anthropometric, clinical, and biochemical parameters. Genomic DNA was extracted from the leukocytes of blood specimens using a standard method. We amplified the ABCC8 rs757110 polymorphic site (T/G) using a polymerase chain reaction (PCR) method and a designed primer pair. To perform the PCR-RFLP method, the amplicons were subjected to restriction enzymes and the resulting fragments separated by gel electrophoresis. RESULTS: The frequency of the G-allele of Ala1369Ser polymorphism was significantly (0.01) higher in the case group than the control group (19% vs. 9%, respectively). In the dominant model (TT vs. TG+GG), there was a significant relationship between this SNP and an increased risk of T2DM (P = 0.00). T2DM patients with TG+GG genotypes had significantly higher fasting plasma insulin and HOMA-IR than those who had the TT genotype (P = 0.02 and 0.01, respectively). CONCLUSION: Our study is the first study to investigate the association between Ala1369Ser ABCC8 genetic variation and T2DM in the Kurdish population of western Iran. The obtained results clearly show that Ala1369Ser polymorphism of ABCC8 is associated with an increased risk of T2DM in this population.