To explore further the role of substance P (SP) in wound healing and scar formation, SP concentrations in wounds of scalded rats were assayed. Expressions of apoptosis-associated genes in fibroblasts cultured with SP were detected. SP concentrations in superficial wounds increased earlier than those in deep wounds. SP was associated with an increased proliferation and a decreased apoptosis of fibroblasts. It had a greater influence on keloid fibroblasts than on hypertrophic scar fibroblasts by elevating the expression of proliferating cell nuclear antigen and BCL-2 in fibroblasts. Spantide completely suppressed the effects of SP on hypertrophic scar fibroblasts, and partly inhibited its effects on keloid scar fibroblasts. SP may play an important role in wound healing by promoting wound fibroblast proliferation and inhibiting apoptosis. It may also participate in pathological scar formation by modulating the expression of apoptosis-associated genes. SP is postulated to play a dual role in wound repair.
The Lando dermal scaffold is a newly developed, tissue-engineered dermal scaffold material. This study sought to observe its vascularization in an acute full-thickness skin-defect porcine model. There were eight Tibetan pigs in this research. Six 5 × 5 cm full-thickness skin-defect wounds were prepared on the dorsal area of each pig, which were divided into two groups. The experimental group wounds were covered by Lando dermal scaffolds, while the other received Vaseline gauzes as blank control. At day 3, 7, 14 and 21 after injury, the general condition of wounds was observed, and wound specimens were obtained for HE staining, Masson staining and the expression of CD31, α-SMA and VEGF, which were examined by immunohistochemistry. The results showed the wounds in the experimental group (Lando) were drier with a lower incidence of infection, and the granulation tissues grew better and smoother than the control group. In the experimental group, the hyperemia, edema and inflammatory reactions were milder, the fibroblasts ingrew earlier, the capillaries grew mostly parallel to the wound surface which resembled normal skin, and the collagen fibers were thicker with more regular arrangement than in the control group. The CD31 + microvessel count, α-SMA + microvessel count and VEGF expression of the experimental group were significantly higher than the control group at day 7 and 14 after injury (p < .05). In conclusion, the Lando dermal scaffold showed good vascularization at day 14 post grafting in an acute full-thickness skin-defect porcine model, which may be associated with increased expression of VEGF.
Objective: The aim of this study was to investigate whether progranulin (PGRN) levels in cerebrospinal fluid (CSF) were associated with postoperative delirium (POD) in geriatric patients undergoing knee replacement.Method: A total of 600 Han Chinese patients aged 65–90 years and who underwent unilateral total knee arthroplasty were included in the Perioperative Neurocognitive Disorder And Biomarker LifestylE (PNDABLE) study from June 2020 to November 2020. All participants were assessed using the Confusion Assessment Method and the Memorial Delirium Assessment Scale on postoperative days 1–7 (or before discharge) by an anesthesiologist. CSF PGRN and CSF biomarkers of POD were measured by ELISA. We analyzed the risk and protective factors of POD using the multivariate logistic regression, and the associations between CSF PGRN and CSF biomarkers of POD using multiple linear regression. We also explored whether the influence of CSF PGRN on POD was mediated by POD core pathology in linear regression models.Results: Postoperative delirium incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN between patients with POD and non-POD (NPOD). As for CSF biomarkers, CSF Aβ40, T-tau, and P-tau were risk factors for POD, while CSF PGRN, Aβ42, and Aβ42/Aβ40 were protective factors for POD, as shown by the multivariate logistic regression analysis. CSF PGRN was positively associated with CSF Aβ42 and was negatively associated with CSF Aβ40, T-tau, and P-tau in patients with POD. We found that the AUC was 0.795 (95% CI = 0.706, 0.867) for PGRN between POD and NPOD groups. We found the influence of CSF PGRN on POD was mediated by POD core pathology. The effect was considered partial mediation with the proportion of mediation varying from 44.92 to 62.07%.Conclusion: Cerebrospinal fluid PGRN may be a reasonably good prognostic factor for POD development. Overall, amyloid pathology and tau protein might partially mediate the influence of PGRN on POD.Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2000033439.
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