The Effect of Low-Level Laser therapy and Curcumin on the Expression of LC3, ATG10 and BAX/BCL2 Ratio in PC12 Cells Induced by 6-Hydroxide Dopamine

Introduction: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. The neuroinflammation in the brain of PD patients is one of the critical processes in the immune pathogenesis of PD leading to the neural loss in the substantia nigra. Due to the anti-inflammatory effects of curcumin (CU) and low-level laser therapy (LLLT), we examined the protective effect of CU and LLLT on PC12 cells treated with 6-hydroxydopamine (6-OHDA) as a Parkinson model.Methods: PC12 cells were pretreated using various concentrations of 6-OHDA for 24 hours to induce oxidative and cellular damages. PC12-6-OHDA cells were co-treated with CU and LLLT. The effects of CU and LLLT on Bax/Bcl2 and LC3/ATG10 expression were analyzed by real-time PCR and cell viability was assessed by MTT assay. Cell A Software was used to calculate the length of the Neurite and cell body areas.Results: The results of this study show that the combination of CU dose-dependently and LLLT has a significant neuroprotective effect on cells and cellular death significantly decreases by increasing CU concentration. CU+LLLT decreases Bax/Bcl2 ratio which is an indicator of apoptosis and it also rescued a decrease in LC3 and ATG10 expression in comparison with 6-OHDA group.Conclusion: This study shows that the combination of 5 μM CU and LLLT has the best neuroprotective effect on PC12 cells against 6-OHDA by decreasing the BAX/BCL2 ratio

Cell Therapy and Tissue Engineering in Bone Defect Reconstruction; A Review

Background: Extensive research on bone tissue engineering as a novel therapeutic approach to design and fabricate suitable scaffolds is in progress to overcome the limitations of conventional bone repair techniques. In recent years, tissue engineering and remedial medicine have come up with the strategy of designing, fabricating, and optimizing synthetic and natural scaffolds containing cells and growth factors to facilitate the direct and indirect mechanisms of bone tissue repair in the body. Based on many studies, cellular source, cell medium condition, and biological scaffolds are critical factors in bone defect repair in the field of tissue engineering.Aim: In this review, we focus on the combination of mesenchymal cells derived from the human adipose tissue, stem cell-to-bone differentiation medium, and biocompatible polyvinyl alcohol-graphene oxide scaffolds in bone lesion repair to gain a better understanding of each factor. This would, in turn, help us design and develop optimal therapeutic approaches for bone repair and regeneration. Conclusion: The combination of mesenchymal cells and biocompatible scaffolds proved promising in the process of bone lesion repair

Neuroprotective Effects of Curcumin on the Proliferation and Viability of Neural Stem Cells against H2O2

Background: Oxidative stress and neuroinflammation have found to be implicated in several neurodegenerative disorders (ND). Neuroprotection against oxidative agents has been proposed as a therapy on the basis that it might prevent neuroinflammation. Curcumin is an anti-oxidant with anti-inflammatory properties which has been proposed to be used as a therapeutic agent in ND.Aim: In this study, we examined the neuroprotective effect of curcumin on neural stem cells (NSCs) exposed to H2O2 as an oxidative injury model.Methods: After culturing NSCs, they were co-treated with curcumin and H2O2, after which their effects were tested on cell viability using MTT assay.Results: Our results indicated that the high concentration of H2O2 significantly promoted cell death. Specifically, after using 250 µM of H2O2, the mortality increased dramatically in comparison with the control groups. On the other hand, the presence of curcumin encouraged cell survival of NSCs treated with H2O2.Conclusion: Our result showed that curcumin has a protective effect on NSCs against H2O2 and it may ameliorate the mortality rate induced by H2O2

Exosome Therapy in Spinal Cord Injury: A Review

Background: Injuries to the spinal cord (SCI) are one of the most detrimental central nervous system (CNS) injuries in developing countries. Today, treatment is one of the major issues facing the medical profession, and to date, there is no known promising treatment capable of fully healing injuries. There are various methods to repair and improve SCI, including the use of stem cells particularly mesenchymal stem cells (MSCs). Various studies have been performed on applying these cells in the treatment of SCI, whose results have confirmed the efficacy of using these cells specifically due to the paracrine secretion of these cells including growth factors, chemokines, cytokines, and small extracellular vesicles. Interestingly, among these paracrine molecules, exosomes may have the maximum therapeutic value and as such is widely investigated by researchers.Aim: to fully focus on the usage of stem cell-derived extracellular vesicles on the healing of SCI in animal models.Conclusion: Taken together, the extracellular nanovesicles have promising therapeutic potentials and their use in the treatment of SCI has been rapidly growing. In this review, we elucidated the effect of exosomes derived from bone marrow MSCs in SCI

Cell Therapy in Hearing Loss Treatment: A Review of Recent Advances

Background: The mammal's inner ear is responsible for hearing and balance. To perform these tasks, it requires the vestibular and cochlear system. Sensor neural hearing loss (SNHL) is the most common type of hearing loss resulting in degeneration of internal sensory hair cell, where cochlear nerve in cochlear stem cell and gene-based strategies provide the opportunity for replacement for these cells.Aim: In this review, we evaluated the efficiency of stem cell therapy in inner ear.Methods: In this study we examined different articles in different databases such as Google Scholar, PubMed, and Elsevier.Results: The stem cells have offered desired results in the delivery of gene and tissue engineering programs. Evidence suggests that stem cells are considered as a promising tool in medical applications thanks to their high plasticity and trophic characteristics.Conclusion: In this review, Stem cell transplantation is widely used in clinical practice, and the source is highly desirable, since the patient's bone marrow cells can be potentially transplanted without any safety problems

The Combined Effects of Mesenchymal Stem Cell Conditioned Media and Low-Level Laser on Stereological and Biomechanical Parameter in Hypothyroidism Rat Model

Introduction: Many studies have shown the positive effect of laser radiation and application of the mesenchymal stem cells (MSCs) and their secretion in stimulating bone regeneration. The aim of this study was determining effects of MSC conditioned media (CM) and low-level laser (LLL) on healing bone defects in the hypothyroid male rat.Methods: We assigned 30 male Wistar rats randomly to 3 groups: control, hypothyroidism, CM+LLL. Four weeks after surgery, the right tibia was removed. Biomechanical examination and histological examinations were performed immediately.Results: Our results showed significant increase in bending stiffness (116.09 ± 18.49), maximum force (65.41 ± 8.16), stress high load (23.30 ± 7.14), energy absorption (34.57 ± 4.10), trabecular bone volume (1.34 ± 0.38) and the number of osteocyte, osteoblast, and osteoclast (12.77 ± 0.54, 6.19 ± 0.80, 1.12 ± 0.16 respectively) in osteotomy site in the LLL + CM group compared to the hypothyroidism group (P < 0.05).Conclusion: The results indicated that using the LLL + CM may improve fracture regeneration and it may hasten bone healing in the hypothyroid rat

Cell Therapy; A New and Safe Strategy for the Treatment of Spinal Cord Injury: A Review

Background: Spinal cord injury is a progressive process that initially causes abnormal nerve connections. Following spinal cord injury, the spinal cord is impaired after which cell death and apoptosis occurs. Primary damage happens in the spinal cord due to the demyelization of the large axons. Cell therapy is among the new strategies that have been considered for the treatment of neural injuries in recent years.Aim: In this narrative review article, we discuss "Cell Therapy" as a new and safe strategy for the treatment of spinal cord injury. we are going to explain the epidemiological and pathophysiological aspects of spinal cord injuries (SCI) as well as SCI experimental and clinical stem cell strategies.Conclusion: There are several promising advancements and findings in the field of stem cell biology and cell reprogramming, with the aim of treating patients with SCI via stem cell therapy. We reviewed critical issues for clinical translation and we also provided a commentary on recent developments such as termination of the first human embryonic stem cell transplantation trial in human SCI

Protective effect of Photobiomodulation Therapy and Bone Marrow Stromal Stem Cells Conditioned Media on Pheochromocytoma Cell Line 12 Against Oxidative Stress Induced by Hydrogen Peroxide

Introduction: Bone marrow stromal stem cells (BMSCs), a type of adult stem cells, secrete bioactive molecules such as trophic factors, growth factors, chemokine and cytokines that may be effective against oxidative stress in neurodegenerative diseases.In this study, we examined the protective effect of BMSCs conditioned media CM) and photobiomodulation therapy (PBMT) on PC12 cells exposed to H2O2 as an oxidative injury model.Methods: BMSCs were cultured and confirmed by flow cytometry analysis and underwent osteogenic and adipogenic differentiation. Then, PC12-H2O2 cells were co-treated with BMSCs-CM and PBMT. The effect of BMSCs-CM and PBMT (He-Ne laser, 632.8 nm, 3 mW, 1.2 J/cm2, 378 s) on Bax/Bcl2 expression, cell viability, was assessed by real-time PCR and MTT assay. The length of the Neurite and cell body areas were assessed by Cell A software.Results: Flowcytometry analysis, as well as osteogenic and adipogenic staining, confirmed the BMSCs. The length of the Neurite was the highest in the group which received CM+PBMT and cell body areas were significant in CM+PBMT compared to other groups. Based on our results, elevating H2O2 concentration increased cell death significantly and using concentrations of 250 μM resulted in a dramatic increase in the mortality compared to the other groups.Conclusion: Our result demonstrated that the combination of CM +PBMT has a protective effect on PC12 cells against oxidative stress

LC3 and ATG5 overexpression and neuronal cell death in the prefrontal cortex of postmortem chronic methamphetamine users

Methamphetamine (METH) abuse is accompanied by oxidative stress, METH-induced neurotoxicity, and apoptosis. Oxidative stress has devastating effects on the structure of proteins and cells. Autophagy is an evolutionarily conserved intracellular regulated mechanism for orderly degradation of dysfunctional proteins or removing damaged organelles. The precise role of autophagy in oxidative stress-induced apoptosis of dopaminergic neuronal cells caused by METH has not clarified completely. In this study, we sought to evaluate the effects of METH abuse on autophagy in the prefrontal cortex of postmortem users, mainly focusing on the ATG5 and LC3 during neuroinflammation. Postmortem molecular and histological examination was done for two groups containing 12 non-addicted and 14 METH addicted cases. ATG5 and LC3 expression were analyzed by real-time PCR and immunohistochemistry (IHC) methods. Histopathological analysis was performed by stereological cell counting of neuronal cells using Hematoxylin and Eosin (H & E) staining technique. In order to detect DNA damage in the prefrontal lobe, Tunnel staining was performed. Real-time PCR and IHC assay showed overexpression of ATG5 and LC3 protein in the prefrontal cortex of Meth users. The cell death and neuronal degeneration were increased significantly based on Tunel assay and the stereological analysis in the Prefrontal cortex. Chronic METH exposure probably induces ATG5 and LC3 overexpression and neuronal cell death in the Prefrontal cortex of the postmortem cases

Unveiling the Nexus of Cellular Quality Control: Exploring the Interplay Between Ribosome-Associated Protein Quality Control and Mitochondrial Quality Control Pathways

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles. Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors. While the exact mechanisms governing these communications within cellular quality control systems remain unclear, unraveling the complex network connecting organelles is essential for understanding the fundamentals of biological systems and uncovering the causes of their breakdown in various pathological conditions. Despite ongoing research endeavors, fully grasping all the pathways involved in the communication networks of cellular quality control systems remains a work in progress. In this study, utilizing models of Drosophila melanogaster and mammalian cells has revealed a previously unrecognized nexus between two fundamental cellular quality control pathways: the ribosome-associated protein quality control (RQC) and the mitochondrial quality control (MQC). We demonstrated that two key proteins in the ribosomal 40S subunit recycling pathway—USP10/Usp10 and G3BP1/rin, which are components of RQC—play a crucial role not only in ribosomal 40S subunit recycling but also in broader cellular processes beyond the ribosomal context. We demonstrated their role in modulating mitochondrial dynamics and positively tuning the MQC pathway in both Drosophila and mammalian cells. The ribosomal 40S subunit recycling factors bind to the fission-fusion machinery at the dynamic hotspots on mitochondria, regulating the assembly and function of the Endoplasmic reticulum (ER)–mitochondria contact sites (ERMCSs). The overexpression of USP10 and G3BP1 induces changes in the mTOR pathways, central players in cellular metabolic control, suggesting a potential interplay between RQC and broader cellular stress response mechanisms. Intriguingly, our genetic screens in Drosophila uncovered modifiers, such as dZnf598 (a ribosomal collision sensor) and Fmr1 (associated with Fragile X syndrome), adding layers of complexity to the interconnected regulation of RQC and MQC. Furthermore, our exploration extends to the ERMCSs, revealing genetic, physical, and functional interactions with components of the 40S ribosomal recycling complex, including IP3R, VDAC, and MCU. These findings position RQC and MQC on a continuum within the broader cellular quality control network. The 40S ribosomal subunit recycling complex emerges as a dynamic hub, orchestrating communication with other signaling pathways to swiftly respond to changes occurring near the ERMCSs junctions. Such adaptability is essential for cellular responses to proteostasis stress associated with aging and various environmental stressors. This study deepens our understanding of the multifaceted roles played by the 40S ribosomal subunit recycling complex and its associated proteins, USP10/Usp10 and G3BP1/rin, in the intricate web of cellular quality control. It shed light on the molecular underpinnings of RQC regulation highlighting its significance beyond ensuring translation fidelity. Notably, RQC emerges as an integral component of broader cellular stress responses, offering potential insights into the pathogenesis of human diseases marked by proteostasis failure and mitochondrial dysfunction