RESUMO
Exosomes, the naturally secreted nanocarriers of cells, have recently been demonstrated to have therapeutic benefits in a variety of disease models where parent cells are not present. However, the use of exosomes in bone defect regeneration has been unusual, and little is documented about the underlying processes. In recent study we produced and characterized exosomes derived human endometrial mesenchymal stem stromal cells and 58S bioactive glass scaffolds; in following, in this research exosome loaded scaffolds synthetized and release of exosome, porosity and bioactivity of them were assessed. More over the effect of scaffolds on repair of critical-size bone defects in rat's calvaria was evaluated by histological examination and micro computed tomography (µ CT). The findings confirmed that constructed porous scaffolds consistently release exosomes; additionally, in vivo findings including Hematoxilin & Eosin staining, Immunohistochemistry, Masson's trichrome, histomorphometric analysis, and µ CT clarified that our implant has osteogenic properties. We discovered that Exo-treated scaffolds might promote osteogenesis especially compared to pure scaffolds, indicating that produced scaffolds containing exosomes could be a potential replacement in bone tissue engineering.
Assuntos
Exossomos , Vidro , Alicerces Teciduais , Ratos , Humanos , Animais , Alicerces Teciduais/química , Microtomografia por Raio-X , Diferenciação Celular , Regeneração Óssea , Osteogênese , Crânio , PorosidadeRESUMO
OBJECTIVE: The pain-reducing effects of the exercise were exerted through different mechanisms. Knowing more clear mechanisms helps to find more approach that is therapeutic. The objective of the present study is the evaluation of cerebrospinal fluid (CSF) glutamate level alteration in neuropathic pain rats and whether physical activity could modulate it. METHODS: In the present study 104 male Wistar rats weighing 180-220 g were randomly divided into 4 groups (Sham, Sham + Exe, Neuropathy, and Neuropathy + Exe) which in turn each group subdivided into 4 groups according to time points for behavioral testing and CSF sampling (Baseline, 2 weeks, 3 weeks, and 4 weeks). To induction of neuropathy (by chronic constriction injury,), after anesthetizing with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), the animal's right sciatic nerve was exposed and was ligated using four movable catgut chromic suture 4/0. The exercise protocol included 25 min of daily swimming, 5 days a week for 4 weeks. Thermal hyperalgesia and mechanical tactile threshold were detected using the plantar test and Von Frey filaments, respectively. CSF glutamate level was determined using high-performance liquid chromatography. RESULTS: Findings indicated that mechanical and thermal thresholds significantly (p < 0.01, p < 0.05 respectively) decreased in the neuropathy group against that in sham groups. On the other hand, exercise significantly increased mechanical tactile threshold (p < 0.0012) and thermal threshold (p < 0.05) compared to the neuropathy group. Moreover, CSF glutamate level prominently (p < 0.01) was increased in the neuropathy group compared to the sham group, and swimming exercise significantly (p < 0.001) reduced it. IN CONCLUSION: The present findings provide new evidence showing that medium-intensity swimming exercise attenuates pain-like behaviors in neuropathic pain animals, which is possibly due to decreasing CSF glutamate level and its neurotransmission.
Assuntos
Neuralgia , Limiar da Dor , Ratos , Masculino , Animais , Limiar da Dor/fisiologia , Natação , Ratos Sprague-Dawley , Ratos Wistar , Ácido Glutâmico , Hiperalgesia/terapia , Neuralgia/terapiaRESUMO
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.