Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound.

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2-5 than in group 1, we found better results in groups 3-5 than in group 2 (p < 0.05). M1 macrophages in groups 2-5 were lower than in group 1, while groups 3-5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2-5 were greater than in group 1, and groups 3-5 were greater than in group 2. (p ≤ 0.001). Groups 2-5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF- 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.

The Efficacy of Vitamin D Supplement in the Expression and Protein Levels of Endometrial Decidualization Factors in Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a challenging situation for infertility specialists, and its treatment is introduced as a difficult case in the field of assisted reproductive technology (ART). Vitamin D (VD) is one of the supplements that have been suggested to improve the implantation process. In the present study, the effect of VD on the expression and protein levels of VD receptor (VDR), progesterone receptor (PR), prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP-1), and homeobox protein A10 (HOXA10) in the endometrial cells of unknown RIF women with and without VD deficiency were assessed by qRT-PCR and immunohistochemistry. Twelve women with unknown RIF and VD deficiency (≤ 20 ng/ml) and twelve women with unknown RIF without VD deficiency (≥ 30 ng/ml) from 2021 to 2022 were identified. Endometrial specimens were collected in the mid-luteal stage before treatment or pregnancy. In the group with VD deficiency, oral medication of VD 50,000 units was prescribed for 2 to 3 months and their serum levels of VD were re-measured, then an endometrial biopsy at the same stage of the menstrual cycle was performed. The expression and protein levels of VDR, PR, PRL, IGFBP1, and HOXA10 in RIF patients with VD deficiency were lower than the RIF patients without VD deficiency (P value < 0.05). Our findings suggest that VD can play a key role in the pregnancy process, especially during embryo implantation and decidualization of the endometrial cells.IRCT registration number: IRCT20220528055006N1, Registration date: 2022-10-15, Registration timing: retrospective.

Application of combined photobiomodulation and curcumin-loaded iron oxide nanoparticles considerably enhanced repair in an infected, delayed-repair wound model in diabetic rats compared to either treatment alone.

Herein, we attempted to evaluate the therapeutic potential of photobiomodulation (PBM) and curcumin-loaded iron nanoparticles (CUR), alone and in combination, on wound closure rate (WCR), microbial flora by measuring colony-forming units (CFUs), the stereological and biomechanical properties of repairing wounds in the maturation stage of the wound healing course in an ischemic infected delayed healing wound model (IIDHWM) of type I diabetic (TIDM) rats. There were four groups: group 1 was the control, group 2 received CUR, rats in group 3 were exposed to PBM (80 Hz, 890 nm, and 0.2 J/cm2), and rats in group 4 received both PBM and CUR (PBM + CUR). We found CFU was decreased in groups 2, 3, and 4 compared to group 1 (p = 0.000 for all). Groups 2, 3, and 4 showed a considerable escalation in WCR compared to group 1 (p = 0.000 for all). In terms of wound strength parameters, substantial increases in bending stiffness and high-stress load were observed in groups 2, 3, and 4 compared to group 1 (p = 0.000 for all). Stereological examinations revealed decreases in neutrophil and macrophage counts and increases in fibroblast counts in groups 2, 3, and 4compared  to group 1 (p = 0.000 for all). Blood vessel counts were more dominant in the PBM and PBM + CUR groups over group 1 (p = 0.000 for all). CFU and wound strength as well as macrophage, neutrophil, and fibroblast counts were found to be improved in the PBM + CUR and PBM groups compared to the CUR group (ranging from p = 0.000 to p < 0.05). Better results were achieved in the PBM + CUR  treatment  over the PBM therapy. We determined therapy with PBM + CUR, PBM alone, and CUR alone substantially accelerated diabetic wound healing in an IIDHWM of TIDM rats compared to control  group. Concomitantly, the PBM + CUR and PBM groups attained significantly enhanced results for WCR, stereological parameters, and wound strength than the CUR group, with the PBM + CUR results being superior to those of the PBM group.

Alpha lipoic acid ameliorates detrimental effects of maternal lipopolysaccharides exposure on prefrontal white matter in adult male offspring rats.

BACKGROUND: Activation of the maternal immune system by lipopolysaccharide (LPS) increases the production of proinflammatory cytokines, free radicals, and reactive oxygen species (ROS), all of which play a significant role in the pathogenesis of many offspring neurodevelopmental disorders. Alpha Lipoic Acid (ALA) is a natural compound that has anti-inflammatory and antioxidant properties. This study was performed to assess the effect of prenatal exposure to LPS on the prefrontal white matter of rat offspring and evaluate the potential protective effects of ALA co-administration during pregnancy. METHODS: Pregnant Wistar rats were randomly divided into six groups (n = 6 each group): (1) control, (2) received LPS (100 µg/kg, intraperitoneally (IP) on gestational day 9.5 (GD 9.5), (3) received ALA (20 mg/kg) from GD1 to GD11, (4) LPS+ALA received LPS on GD9.5 and ALA from GD1 to GD11, (5 and 6) received LPS and ALA vehicle respectively. In each group, 21-day old male offspring (2 male pups from each mother) was harvested, and then their prefrontal white matter was separated and prepared for the ultrastructural, stereological, and molecular assays. RESULTS: In utero exposure to LPS led to a significant decrease in nerve cell counts, ultrastructural alterations in myelinated axons, and abnormal changes in genes expression of Sox10,Olig1,yrf,Wnt in the prefrontal of the rat offspring. Co-administration of ALA resulted in amelioration of those abnormal changes in the LPS rat offspring. CONCLUSION: The findings of our preclinical study, explore that prenatal ALA treatment efficiently protects the nervous system against LPS induced abnormal changes in the offspring.

Peripubertal stress following maternal immune activation sex-dependently alters depression-like behaviors in offspring.

There is an increasing evidence that maternal immune activation can render the offspring more vulnerable to the impacts of peripubertal stress on behavioral abnormalities in adulthood. The aim of this study was to investigate the combined effects of maternal immune activation and peripubertal stress on depression-related behaviors in male and female offspring. Pregnant mice were treated with lipopolysaccharides (LPS) or vehicle, and then offspring were subjected to stressful conditions or left unstressed during peripubertal period. Four behavioral tests including novelty-suppressed feeding test, sucrose preference test, tail suspension test, and forced swim test were used to measure depression-related behaviors in offspring. The activity of hypothalamic-pituitary-adrenal (HPA) or - gonadal (HPG) axes were also evaluated by measuring basal and stress-induced corticosterone, testosterone and estradiol levels in the serum of offspring. Our findings revealed that mild maternal immune activation and peripubertal stress interacted synergistically to induce depression-related symptoms and HPA axis hyperactivity in male offspring, whereas no significant changes were observed in female offspring. We also found that this combination of environmental factors significantly decreased serum testosterone and estradiol levels in adult male and female offspring respectively. There were also significant correlations between behavioral parameters and hormones. Taken together, these findings show that the combination of two environmental risk factors can predispose the male offspring to increased depression-related symptoms in adulthood as compared to the females. This study suggests that the combination of maternal immune activation and peripubertal stress can alter depression-related behaviors and HPA axis function in a sex-dependent manner.

Sciatic nerve injury alters the spatial arrangement of neurons and glial cells in the anterior horn of the spinal cord.

The spatial arrangement of the cell is important and considered as underlying mechanism for mathematical modeling of cell to cell interaction. The ability of cells to take on the characteristics of other cells in an organism, it is important to understand the dynamical behavior of the cells. This method implements experimental parameters of the cell-cell interaction into the mathematical simulation of cell arrangement. The purpose of this research was to explore the three-dimensional spatial distribution of anterior horn cells in the rat spinal cord to examine differences after sciatic nerve injury. Sixteen Sprague-Dawley male rats were assigned to control and axotomy groups. Twelve weeks after surgery, the anterior horn was removed for first- and second-order stereological studies. Second-order stereological techniques were applied to estimate the pair correlation and cross-correlation functions using a dipole probe superimposed onto the spinal cord sections. The findings revealed 7% and 36% reductions in the mean volume and total number of motoneurons, respectively, and a 25% increase in the neuroglial cell number in the axotomized rats compared to the control rats. In contrast, the anterior horn volume remained unchanged. The results also indicated a broader gap in the pair correlation curve for the motoneurons and neuroglial cells in the axotomized rats compared to the control rats. This finding shows a negative correlation for the distribution of motoneurons and neuroglial cells in the axotomized rats. The cross-correlation curve shows a negative correlation between the motoneurons and neuroglial cells in the axotomized rats. These findings suggest that cellular structural and functional changes after sciatic nerve injury lead to the alterations in the spatial arrangement of motoneurons and neuroglial cells, finally affecting the normal function of the central nervous system. The experimental protocol was reviewed and approved by the Animal Ethics Committee of Shahid Beheshti University of Medical Sciences (approval No. IR.SBMU.MSP.REC1395.375) on October 17, 2016.