Autophagy-induced mesenchymal stem cell-derived extracellular vesicles ameliorated renal fibrosis in an in vitro model.

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-ß1), 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-ß1, 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-ß1, 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.

Repairing rat calvarial defects by adipose mesenchymal stem cells and novel freeze-dried three-dimensional nanofibrous scaffolds.

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.

Photobiomodulation Therapy and Cell Therapy Improved Parkinson's Diseases by Neuro-regeneration and Tremor Inhibition.

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.

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).

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, 632.8nm, 3mW, 1.2J/ cm2 , 378s) 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.

Stem cell transplantation and functional recovery after spinal cord injury: a systematic review and meta-analysis.

Spinal cord injury is a significant cause of motor dysfunctions. There is no definite cure for it, and most of the therapeutic modalities are only symptomatic treatment. In this systematic review and meta-analysis, the effectiveness of stem cell therapy in the treatment of the spinal cord injuries in animal models was studied and evaluated. A systematic search through medical databases by using appropriate keywords was conducted. The relevant reports were reviewed in order to find out cases in which inclusion and exclusion criteria had been fulfilled. Finally, 89 articles have been considered, from which 28 had sufficient data for performing statistical analyses. The findings showed a significant improvement in motor functions after cell therapy. The outcome was strongly related to the number of transplanted cells, site of injury, chronicity of the injury, type of the damage, and the induction of immune-suppression. According to our data, improvements in functional recovery after stem cell therapy in the treatment of spinal cord injury in animal models was noticeable, but its outcome is strongly related to the site of injury, number of transplanted cells, and type of transplanted cells.

Endoscopic Transnasal Approach for Cholesterol Granuloma of the Petrous Apex.

Cholesterol granulomas are rare round or ovoid cysts. They contain cholesterol crystals surrounded by foreign bodies of giant cells and are characterized by chronic inflammation. Large cholesterol granuloma can compress surrounding tissue especially cranial nerves. There are several types of surgery for the resection of cholesterol granuloma. We describe 4 cases of cholesterol granuloma operated on via transnasal endoscopic approach. In this report, we describe radiologic and pathologic features of this lesion and explain the advantages and disadvantages of transsphenoidal endoscopic approach for these rare lesions.

Neuro-otologic manifestations of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) has numerous neurologic signs and symptoms, including hearing impairment. The reports concerning the type and severity of hearing loss in MS patients vary and little is known about an association of the disease characteristics with changes in hearing status. OBJECTIVE: To find the otologic and neuro-otologic manifestations of MS with the use of routine hearing assessment tools. METHODS: The presence of neuro-otologic signs and symptoms were studied in 30 patients diagnosed with MS. Patients underwent pure tone audiometry, speech audiometry and acoustic brain stem response (ABR) tests. The results were compared with 30 healthy age and sex matched controls. RESULTS: The most common finding was sensory-neural hearing loss followed by dizziness and nystagmus. The shape of the audiogram and severity of hearing loss was associated with both chronicity and disease activity. There were abnormal latencies in ABR waves which were more significant with high velocity stimulus. CONCLUSION: Hearing status deserves careful attention in MS patients. It may be used as a diagnostic means or an indicator for evaluating the characteristics of the underlying disease.