Exosomes derived from human placental mesenchymal stem cells in combination with hyperbaric oxygen synergically alleviates spinal cord ischemia-reperfusion injury.

Spinal cord ischemia-reperfusion injury (IR) is a terrible non-traumatic injury that occurs after abdominal aortic occlusion and causes serious damage to neurological function. Several treatment strategies have been suggested for IR, but they were not unable to effectively improve these conditions. Herein we investigated whether exosomes derived from human placental mesenchymal stem cells (hpMSCs-Exos) in combination with hyperbaric oxygen (HBO) could alleviate injury and promote recovery in IR rats. Eighty male Sprague-Dawley rats were randomly allocated into five equal groups. In addition to the control group that only underwent laparotomy, IR animals were planned into four groups as follows: IR group; IR-Exos group; IR-HBO group; and IR-Exos + HBO group. Neurological function evaluated before, 6 h, 12 h, 24 h, and 48 h after injury. After the last neurological evaluation, tissue samples were obtained for stereological, biochemical, and molecular assessments. Our results indicated that the neurological function scores (MDI), the numerical density of neurons, the levels of antioxidative factors (GSH, SOD, and CAT), and anti-inflammatory cytokine (IL-10) were considerably greater in treatment groups than in the IR group, and these changes were more obvious in the IR-Exos + HBO ones. This is while the numerical density of glial cells, the levels of an oxidative factor (MDA) and inflammatory cytokines (IL-1ß, TNF-α, and IL-18), as well as the expression of an apoptotic protein (caspase-3) were meaningfully decreased in treatment groups, especially IR-Exos + HBO group, compared to the IR group. Generally, it was found that co-administration of hpMSCs-Exos and HBO has synergistic neuroprotective effects in the rats undergoing IR.

Exosomes derived from human adipose mesenchymal stem cells loaded bioengineered three-dimensional amniotic membrane-scaffold-accelerated diabetic wound healing.

The occurrence of wounds and defects in the healing process is one of the main challenges in diabetic patients. Herein, we investigated whether adipose-derived stem cells (ADSCs)-derived exosomes loaded bioengineered micro-porous three-dimensional amniotic membrane-scaffold (AMS) could promote healing in diabetic rats. Sixty diabetic rats were randomly allocated into the control group, exosome group, AMS group, and AMS + Exo group. On days 7, 14, and 21, five rats from each group were sampled for stereological, immunohistochemical, molecular, and tensiometrical assessments. Our results indicated that the wound closure rate, the total volumes of newly formed epidermis and dermis, the numerical densities of fibroblasts and proliferating cells, the length density blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably greater in the treated groups than in the control group, and these changes were more obvious in the AMS + Exo ones. Furthermore, the expression of TGF-ß, bFGF, and VEGF genes was meaningfully upregulated in all treated groups compared to the control group and were greater in the AMS + Exo group. This is while expression of TNF-α and IL-1ß, as well as cell numerical densities of neutrophils, M1 macrophages, and mast cells decreased more considerably in the AMS + Exo group in comparison with the other groups. Generally, it was found that using both AMS transplantation and ADSCs-derived exosomes has more effect on diabetic wound healing.

Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a critical medical condition during which sensorimotor function is lost. Current treatments are still unable to effectively improve these conditions, so it is important to pay attention to other effective approaches. Currently, we investigated the combined effects of human placenta mesenchymal stem cells (hPMSCs)-derived exosomes along with hyperbaric oxygen (HBO) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley (SD) rats were allocated into five equal groups, including; sham group, SCI group, Exo group (underwent SCI and received hPMSCs-derived exosomes), HBO group (underwent SCI and received HBO), and Exo+HBO group (underwent SCI and received hPMSCs-derived exosomes plus HBO). Tissue samples at the lesion site were obtained for the evaluation of stereological, immunohistochemical, biochemical, molecular, and behavioral characteristics. Findings showed a significant increase in stereological parameters, biochemical factors (GSH, SOD, and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in treatment groups, especially Exo+HBO group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells and gliosis, as well as expression of inflammatory genes (TNF-α and IL-1ß) were considerably reduced in treatment groups, especially Exo+HBO group, compared to SCI group. We conclude that co-administration of hPMSCs-derived exosomes and HBO has synergistic neuroprotective effects in animals undergoing SCI.

Preclinical and Clinical Applications of Photobiomodulation Therapy in Sperm Motility: A Narrative Review.

About 50% of infertility problems are related to male factors and reduced sperm motility. The important factor that affects the structure and function of sperm is reactive oxygen species (ROS), and over-concentration of ROS reduces the quality and motility of sperm. Photobiomodulation therapy (PBMT) using red to near-infrared (NIR) light is useful in oxidative stress restoration. It plays a therapeutic role in disorders such as asthenospermia, oligospermia cases, and cryopreserved sperm. It also enhances the metabolic capacity of sperm and increases the low-level and non-harmful intracellular content of Ca2+, nitric oxide (NO), and ROS in the stressed cells. Likewise, it modulates survival intracellular pathways and maintains the motility, viability, DNA, and acrosome integrity of sperm. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of semen PBMT.

Effects of chronic hypoxia on the expression of seladin-1/Tuj1 and the number of dark neurons of hippocampus.

BACKGROUND: There are evidences showing the relation between chronic hypoxia and Alzheimer's disease (AD) as a metabolic neurodegenerative disease. This study was designed to evaluate the effects of chronic hypoxia on factors which characterized in AD to introduce a new model of AD-dementia. METHODS AND MATERIALS: Twenty-four male rats were randomly divided in three groups: Control group (Co), Sham group (Sh), Hypoxia induction group (Hx, exposed to hypoxic chamber [oxygen 8% and nitrogen 92%] for 30 days, 4 h/day). Spatial learning and memory were analyzed using the Morris water maze task. At day 30 after hypoxia period, animals were sacrificed and serum was gathered for pro-inflammatory cytokines (interleukin-1ß and tumor necrosis factor) measurements and brains were used for molecular and histopathological investigations. RESULTS: According to behavioral studies, a significant impairment was seen in Hx group (P < 0.05). TNF-α and IL-1ß showed a significant enhanced in Hx group comparing with Co group and Sh group (P < 0.05). As well, the gene expression of seladin-1, Tuj1 and the number of seladin-1+, Tuj1+neurons significantly decreased and also the mean number of dark neurons significantly increased in CA1 and CA3 regions of hippocampus. CONCLUSIONS: In this study, a new model of AD was developed which showed the underlying mechanisms of AD and its relations with chronic hypoxia. Hypoxia for 30 days decreased seladin-1, Tuj1 expression, increased the number of dark neurons, and also induced memory impairment. These results indicated that chronic hypoxia mediated the dementia underlying AD and AD-related pathogenesis in rat.

Flaxseed Can Reduce Hypoxia-Induced Damages in Rat Testes.

BACHGROUND: Hypoxia causes detrimental effects on the structure and function of tissues through increased production of reactive oxygen species that are generated during the re-oxygenation phase of intermittent and continuous hypobaric hypoxia. This study was carried out to evaluate the effects of flaxseed (Fx) in reducing the incidence of hypoxia in rat testes. MATERIALS AND METHODS: In this experimental study, 24 adult Wistar rats were randomly divided into four groups: i. Control group (Co) that received normal levels of oxygen and food, ii. Sham group (Sh) that were placed in hypoxia chamber but received normal oxygen and food, iii. Hypoxia induction group (Hx) that were placed in hypoxia chamber and treated with normal food, iv. Hypoxia induction group (Hx+Fx) that were placed in hypoxia chamber and treated with 10% flaxseed food. Both the Hx and Hx+Fx groups were kept in a hypoxic chamber for 30 days; during this period rats were exposed to reduced pressure (oxygen 8% and nitrogen 92%) for 4 hours/day. Then, all animal were sacrificed and their testes were removed. Malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were evaluated in the testis tissue. Tubular damages were examined using histological studies. Blood samples and sperm were collected to assess IL-18 level and measure sperms parameters, respectively. All data were analyzed using SPPSS-22 software. One way-ANOVA or Kruskal-Wallis tests were performed for statistical analysis. RESULTS: A significant difference was recorded in the testicular mass/body weight ratio in Hx and Hx+Fx groups in comparison to the control (P=0.003 and 0.027, respectively) and Sh (P=0.001 and 0.009, respectively) groups. The sperm count and motility in Hx+Fx group were significantly different from those of the Hx group (P=0.0001 and 0.028, respectively) .Also sperm viability (P=0.0001) and abnormality (P=0.0001) in Hx+Fx group were significantly different from Hx group. CONCLUSION: This study therefore suggests that the oral administration of flaxseed can be useful for prevention from the detrimental effects of hypoxia on rat testes structure and sperm parameters.

Lipid Peroxidation and Its Role in the Expression of NLRP1a and NLRP3 Genes in Testicular Tissue of Male Rats: a Model of Spinal Cord Injury

BAckground: The majority of male patients with spinal cord injury (SCI) suffer from infertility. Nucleotide-binding oligomerization domain-like receptors NOD-like receptors (NLRs) are a kind of receptors that corporate in the inflammasome complex. Recent studies have introduced the inflammasome as the responsible agent for secreting cytokines in semen. Reactive oxygen species (ROS) is one of the elements that trigger inflammasome activation. Genital infections in SCI can lead to ROS generation. We investigated the relation between lipid peroxidation and inflammasome complex activity in testicular tissue of SCI rats. Methods: Adult male rats (n=20), weighting 200-250 g, were included and divided into four groups: three experimental groups, including SCI1, SCI3, and SCI7, i.e. the rats were subjected to SCI procedure and sacrificed after one, three, and seven days, respectively and a control group. We performed a moderate, midline spinal contusion injury at thoracic level 10. The animals were anesthetized, and testes were collected for measurement of gene expression by real-time PCR. Caudal parts of epididymis were collected for malondialdehyde (MDA) measurement. Results: No NLRP1a mRNA over expression was seen in the testes of control and SCI groups. After seven days from SCI surgery, NLRP3 mRNA expression was significantly increased in SCI7 animals (P≤0.05). There was a significant difference in MDA level in SCI7 versus control group, as well as SCI1 and SCI3 animals (P≤0.05). Conclusion: NLRP3 overexpression occurs due to the increased ROS production in testicular tissue of SCI rats.