An ADSC-loaded dermal regeneration template promotes full-thickness wound healing.

Introduction: Full-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal regeneration template (DRT) would improve the efficacy of ADSC grafting and promote full-thickness wound healing. Methods: ADSCs from human adipose tissue were isolated, expanded, and labeled with a cell tracker. Labeled ADSCs were loaded onto the DRT. The viability, the location of ADSCs on the DRT, and the abundance of ADSCs in the wound area were confirmed using CCK8 and fluorescence microscopy. Full-thickness wounds were created on Bama minipigs, which were applied with sham, ADSC, DRT, and ADSC-DRT. Wounds from the four groups were collected at the indicated time and histological analysis was performed. RNA-seq analysis was also conducted to identify transcriptional differences among the four groups. The identified genes by RNA-seq were verified by qPCR. Immunohistochemistry and western blotting were used to assess collagen deposition. In vitro, the supernatant of ADSCs was used to culture fibroblasts to investigate the effect of ADSCs on fibroblast transformation into myofibroblasts. Results: ADSCs were successfully isolated, marked, and loaded onto the DRT. The abundance of ADSCs in the wound area was significantly greater in the ADSC-DRT group than in the ADSC group. Moreover, the ADSC-DRT group exhibited better wound healing with improved re-epithelialization and denser collagen deposition than the other three groups. The RNA-seq results suggested that the application of the integrated ADSC-DRT system resulted in the differential expression of genes mainly associated with extracellular matrix remodeling. In vivo, wounds from the ADSC-DRT group exhibited an earlier increase in type III collagen deposition and alleviated scar formation. ADSCs inhibited the transformation of fibroblasts into myofibroblasts, along with increased levels of CTGF, FGF, and HGF in the supernatant of ADSCs. Wounds from the ADSC-DRT group had up-regulated expressions of CTGF, HGF, FGF, and MMP3. Conclusion: The integral of ADSC-DRT increased the efficacy of ADSC grafting, and promoted full-thickness wound healing with better extracellular matrix remodeling and alleviated scar formation.

An integrated transcriptome, metabolomic, and physiological investigation uncovered the underlying tolerance mechanisms of Monochoria korsakowii in response to acute/chronic cadmium exposure.

Identifying the physiological response and tolerance mechanism of wetland plants to heavy metal exposure can provide theoretical guidance for an early warning for acute metal pollution and metal-contaminated water phytoremediation. A hydroponic experiment was employed to investigate variations in the antioxidant enzyme activity, chlorophyll content, and photosynthesis in leaves of Monochoria korsakowii under 0.12 mM cadmium ion (Cd2+) acute (4 d) and chronic (21 d) exposure. Transcriptome and metabolome were analyzed to elucidate the underlying defensive strategies. The acute/chronic Cd2+ exposure decreased chlorophyll a and b contents, and disturbed photosynthesis in the leaves. The acute Cd2+ exposure increased catalase activity by 36.42%, while the chronic Cd2+ exposure markedly increased ascorbate peroxidase, superoxide dismutase, and glutathione peroxidase activities in the leaves. A total of 2 685 differentially expressed genes (DEGs) in the leaves were identified with the plants exposed to the acute/chronic Cd2+ contamination. In the acute Cd2+ exposure treatment, DEGs were preferentially enriched in the plant hormone transduction pathway, followed by phenylrpopanoid biosynthesis. However, the chronic Cd2+ exposure induced DEGs enriched in the biosynthesis of secondary metabolites pathway as priority. With acute/chronic Cd2+ exposure, a total of 157 and 227 differentially expressed metabolites were identified in the leaves. Conjoint transcriptome and metabolome analysis indicated the plant hormone signal transduction pathway and biosynthesis of secondary metabolites was preferentially activated by the acute and chronic Cd2+ exposure, respectively. The phenylpropanoid pathway functioned as a chemical defense, and the positive role of deoxyxylulose phosphate pathway in leaves against acute/chronic Cd2+ exposure was impaired.

[Phenylpropanoid pathway in plants and its role in response to heavy metal stress: a review].

Phenylpropanoid metabolic pathway is one of the most important secondary metabolic pathways in plants. It directly or indirectly plays an antioxidant role in plant resistance to heavy metal stress, and can improve the absorption and stress tolerance of plants to heavy metal ions. In this paper, the core reactions and key enzymes of the phenylpropanoid metabolic pathway were summarized, and the biosynthetic processes of key metabolites such as lignin, flavonoids and proanthocyanidins and relevant mechanisms were analyzed. Based on this, the mechanisms of key products of phenylpropanoid metabolic pathway in response to heavy metal stress were discussed. The perspectives on the involvement of phenylpropanoid metabolism in plant defense against heavy metal stress provides a theoretical basis for improving the phytoremediation efficiency of heavy metal polluted environment.

Tolerance mechanism and phytoremediation potential of Pistia stratiotes to zinc and cadmium co-contamination.

Pistia stratiotes can not only effectively remediate eutrophic water, but also displays strong absorption and bioaccumulation abilities for heavy metals. However, it has not been well-understood how the plant resists the combined stress of heavy metals. In these experiments, the morphophysiological traits, the ascorbate-glutathione (AsA-GSH) cycle, the glyoxalase system, and the contents of zinc (Zn) and cadmium (Cd) were investigated under Zn and Cd co-pollution. The AsA-GSH cycle and glyoxalase system could coordinately alleviate the oxidative and carbonyl stress, which was identified as an important tolerance mechanism. With Zn50Cd1, Zn50Cd10, Zn100Cd1, and Zn100Cd10 treatments for 18 days, 90.75-93.69% of Zn and 88.13-96.96% Cd accumulated in the roots. Treatments with Zn50Cd50, and Zn100Cd50 for 18 days resulted in a decrease of stress tolerance and chlorophyll content in leaves, an increase in plasma membrane permeability, a massive accumulation of methylglyoxal (MG), and visible toxic symptoms. Additionally, the bioaccumulation factor (BCF) for roots and shoots and the translocation factor (TF) were >1, and the content of Cd in shoots was no <100 mg·kg-1. This indicated P. stratiotes was a Cd hyperaccumulator and have great potential for the phytoremediation of heavy metal contaminated water.Novelty statement Pistia stratiotes, a cadmium hyperaccumulator, has great application potential for the phytoremediation of zinc and cadmium co-polluted water.

Cardioprotective effects of rat adipose­derived stem cells differ under normoxic/physioxic conditions and are associated with paracrine factor secretion.

Adipose tissue­derived stem cells (ASCs) are beneficial for myocardial regeneration. The physiological oxygen content of human organs is estimated to range between 1 and 11%. However, in the majority of previous in vitro studies with cultured ASCs, the O2 concentration was artificially set to 21%. The present study aimed to compare the protective effects of rat ASCs on neonatal rat ventricular myocytes (NRVMs) under normoxic (21% O2) and physioxic (5% O2) conditions. Rat NRVMs cultured under normoxia or physioxia were treated with H2O2 or left untreated, and further co­cultured with ASCs in 21% or 5% O2. The apoptosis of NRVMs was evaluated by Annexin V staining and quantitating the protein levels of Bcl­2 and Bax by western blotting. The oxidative stress of NRVMs was determined by a glutathione/oxidized glutathione assay kit. The concentrations of secreted vascular endothelium growth factor (VEGF), insulin like growth factor­1 (IGF­1) and basic fibroblast growth factor (bFGF) in the culture medium were quantified by enzyme­linked immunosorbent assay. Under both normoxia and physioxia, co­culture with ASCs protected H2O2­exposed NRVMs from apoptosis and significantly alleviated the oxidative stress in NRVMs. The protective effects of ASCs were associated with increased secretion of VEGF, IGF­1 and bFGF. ASCs cultured in 5% O2 exhibited certain cardioprotective effects against H2O2 stress. The results of the present study suggested that O2 concentrations influenced the cardioprotective effects of ASCs. VEGF, IGF­1 and bFGF may serve a role in the myocardial regeneration mediated by transplanted ASCs.

First-time versus recurrent penoscrotal extramammary Paget's disease: Clinicopathological characteristics and risk factors in 164 Chinese male patients.

BACKGROUND: Penoscrotal extramammary Paget's disease is a rare, slow-growing neoplasm with high frequency of local recurrence. AIMS: The aim of this study was to investigate the difference in clinicopathological characteristics between first-time and recurrent penoscrotal Paget's disease, and to discover the potential risk factors of recurrence. METHODS: Between January 2007 and February 2014, a total of 164 Chinese patients with biopsy-proven tramammary Paget's diseaseex in penis and scrotum underwent wide local resection in our institution. Among them, 142 patients with first-time disease and other 22 patients with recurrent disease were enrolled in this retrospective analysis. RESULTS: The median duration of symptoms was much shorter in recurrent disease than in first-timers (3 vs. 24 months, P < 0.001). Patients with recurrent disease tended to have lower lesion exudation rates (27.3% vs. 51.8%, P= 0.032). In addition, patients with distant stage were more likely to obtain recurrent disease compared with first-time disease (P = 0.005). Through immunohistochemical detection of extramammary Paget's specimen, we found that HER2/neu protein expression in the recurrent group was significantly higher than first-timers (P = 0.036). LIMITATIONS: In this study, the information on familial history of most patients was insufficient. Moreover, due to the lack of follow-up data of our included cases, we were unable to evaluate the prognosis after diagnosis of extramammary Paget's disease. CONCLUSION: Patients with penoscrotal Paget's disease, especially those with shorter duration of symptoms, exudation of lesions, distant-stage, Paget cells infiltrating into adnexa, and HER2/neu expression, should be followed up more carefully after surgery, as they were more likely to suffer recurrence.

Safety and Efficacy of Facial Fat Grafting Under Local Anesthesia.

BACKGROUND: Facial fat grafting under local anesthesia has been widely performed in outpatient departments and private settings in China. The present study aimed to evaluate the safety and efficacy of facial fat grafting under local anesthesia. METHOD: A retrospective study was conducted on 155 patients who underwent facial fat grafting. The clinical data were recorded. Preoperative and postoperative two-dimensional images were acquired to evaluate the effect of facial fat grafting on refining facial contouring, rejuvenation as well as deformity reconstruction. The complications were recorded to assess the safety of the approach. RESULT: All the facial fat grafting procedures were performed successfully under local anesthesia. A majority of the patients who underwent one or more sessions of facial fat grafting under local anesthesia were satisfied with the cosmetic results. No severe complications occurred in these patients. CONCLUSIONS: In the present study, remarkable and natural improvements of facial contouring, rejuvenation as well as deformity reconstruction were achieved with facial fat grafting in most patients. Thus, the procedures performed under local anesthesia by experienced surgeons are safe. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .