Background Large area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originating from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel ...promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing. Methods hADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis. Results Compared with hADSCs-Exos or PF-127 only, PF-127/hADSCs-Exos complexes enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, alpha-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), up-regulated expression of skin barrier proteins (KRT1, AQP3), and reduced inflammation (IL-6, TNF-alpha, CD68, CD206). By using PF-127/hADSCs-Exos complexes, hADSCs-Exos can be administrated at lower doses frequency while maintaining the same therapeutic effects. Conclusion Administration of hADSCs-Exos in PF-127 improves the efficiency of exosome delivery, maintains the bioactivity of hADSCs-Exos, and optimizes the performance of hADSCs-Exos. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds. Keywords: Wound healing, Adipose-derived mesenchymal stem cells, Exosomes, PF-127 hydrogel
Cutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived ...mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing.
hADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis.
Combined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha.
Our findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.
The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in ...fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose‐dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p < 0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein‐rich foods that are subsequently fried.
Summary
The aim of the study was to evaluate the effect of Chinese quince proanthocyanidins (PAs) on the deterioration and heterocyclic aromatic amine (HAA) formation in soybean oil when used for ...deep‐fat frying, one tea polyphenol (Tea‐PP) and two PAs (PA‐100 and PA‐140) (200 mg/kg) were added to soybean oils. While all three retarded the accumulation of oil degradation products and enhanced performance of frying oil, as well as reduced the formation of HAAs, both PA‐100 and PA‐140 performed better than Tea‐PP. Adding PA‐100 and PA‐140 not only decreased the increase in oxidation indices and lossy of tocopherols but also inhibited HAA formation by 14.82%–30.64% and 19.52%–54.24%, respectively. Multivariate analysis revealed that PA‐140 always had a stronger effect than PA‐100 in concurrently enhancing frying performance and suppressing the generation of HAAs. This study provides evidence for using PAs from Chinese quince as the stabilisers of frying oils and inhibitors of HAA formation in these oils in the food industry.
Chinese quince proanthocyanidins enhance frying performance and suppress heterocyclic aromatic amine formation in soybean oil.
Aberrant microRNA expression is involved in the regulation of various cellular processes, such as proliferation and metastasis in multiple diseases including cancers. MicroRNA‐30e‐5p (miR‐30e) was ...previously reported as an oncogenic or tumour suppressing miRNA in some malignancies, but its function in lung adenocarcinoma (LAC) remains largely undefined. In this study, we found that the expression of miR‐30e was increased in LAC tissues and cell lines, associated with tumour size and represented an independent prognostic factor for overall survival and recurrence of LAC patients. Further functional experiments showed that knockdown of miR‐30e suppressed cell growth while its overexpression promoted growth of LAC cells and xenografts in vitro and in vivo. Mechanistically, PTPN13 was identified as the direct target of miR‐30e in LAC, in which PTPN13 expression was down‐regulated in LAC tissues and showed the inverse correlation with miR‐30e expression. Overexpression of PTPN13 inhibited cell growth and rescued the proliferation‐promoting effect of miR‐30e through inhibition of the EGFR signalling. Altogether, our findings suggest that miR‐30e could function as an oncogene in LAC via targeting PTPN13 and act as a potential therapeutic target for treating LAC.
Summary
Proanthocyanidins with different polymerisation degrees were extracted from Chinese quince fruits by subcritical ethanol/water into four fractions (F1‐F4), which were then analysed using ...UPLC‐MS/MS, GPC and thiolysis combined with RP‐HPLC MS and MALDI‐TOF MS (matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry). The inhibitory effects of these proanthocyanidins on the formation of heterocyclic aromatic amines (HCAs), such as norharman, harman and PhIP, in chemical model systems were determined. The results reflected that the mean degree of polymerisation (DP) of proanthocyanidins in fractions F1, F2, F3 and F4 were 8.0, 12.7, 27.5 and 64.9, respectively. All four fractions prominently and dose‐dependently reduced the formation of HCAs at concentrations of 0.5, 1 and 2 mg mL−1 in chemical models. F1, the fraction richest in oligomers, had the most effective inhibition of harman, norharman and PhIP, with the levels reduced by 65.71%, 37.15% and 72.99%, respectively, when used at a concentration of 2 mg mL−1. The mean DP of proanthocyanidins showed negative correlation with the inhibition of HCA formation (R2= −0.697 for norharman, −0.799 for PhIP and −0.758 for harman). These findings suggest that proanthocyanidins from Chinese quince fruit have the potential to be used as additives to reduce the levels of heterocyclic amines in foods.
Proanthocyanidins with different polymerization degrees, which were extracted from Chinese quince fruits, can effectively prevent the formation of heterocyclic aromatic amines in chemical model systems.
The aim of this study was to investigate the correlations between serum calcium and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). In this retrospective study, serum calcium ...levels, hormone levels and clinical laboratory parameters on admission were recorded. The clinical outcome variables were also recorded. From February 10 to February 28, 2020, 241 patients were enrolled. Of these patients, 180 (74.7%) had hypocalcemia on admission. The median serum calcium levels were 2.12 (IQR, 2.04-2.20) mmol/L, median parathyroid hormone (PTH) levels were 55.27 (IQR, 42.73-73.15) pg/mL, and median 25-hydroxy-vitamin D (VD) levels were 10.20 (IQR, 8.20-12.65) ng/mL. The serum calcium levels were significantly positively correlated with VD levels (
=0.004) but negatively correlated with PTH levels (
=0.048). Patients with lower serum calcium levels (especially ≤2.0 mmol/L) had worse clinical parameters, higher incidences of organ injury and septic shock, and higher 28-day mortality. The areas under the receiver operating characteristic curves of multiple organ dysfunction syndrome, septic shock, and 28-day mortality were 0.923 (
<0.001), 0.905 (
=0.001), and 0.929 (
<0.001), respectively. In conclusion, serum calcium was associated with the clinical severity and prognosis of patients with COVID-19. Hypocalcemia may be associated with imbalanced VD and PTH levels.
Objective: Meta-analysis to evaluate complications in the use of autogenous bone and bone substitutes and to compare bone substitutes, specifically HA, polyetheretherketone (PEEK) and titanium ...materials.
Methods: Search of PubMed, Cochrane, Embase and Google scholar to identify all citations from 2010 to 2019 reporting complications regarding materials used in cranioplasty.
Results: 20 of 2266 articles met the inclusion criteria, including a total of 2913 patients. The odds of overall complication were significantly higher in the autogenous bone group (n = 214/644 procedures, 33.2%) than the bone substitute groups (n = 116/436 procedures, 26.7%, CI 1.29-2.35, p < 0.05). In bone substitutes groups, there was no significant difference in overall complication rate between HA and Ti (OR, 1.2; 95% CI, 0.47-3.14, p = 0.69). PEEK has lower overall complication rates (OR, 0.51; 95% CI, 0.30-0.87, p = 0.01) and lower implant exposure rates (OR, 0.17; 95% CI, 0.06-0.53, p = 0.002) than Ti, but there was no significant difference in infection rates and postoperative hematoma rates.
Conclusions: Cranioplasty is associated with high overall complication rates with the use of autologous bone grafts compared with bone substitutes. PEEK has a relatively low overall complication rates in substitutes groups, but still high infection rates and postoperative hematoma rates. Thus, autologous bone grafts should only be used selectively, and prospective long-term studies are needed to further refine a better material in cranioplasty.
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In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed ...that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications.
Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.
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