Bioactive Wound Healing 3D Structure Based on Chitosan Hydrogel Loaded with Naringin/Cyclodextrin Inclusion Nanocomplex.

The current assay aimed to fabricate and analyze a potent wound healing structure based on a naringin (Nar)/ß-cyclodextrin (ß-CD)-loaded chitosan hydrogel. Using the simulation studies, we assessed the interactions among the Nar, ß-CD, and the formation of the inclusion complex. Then, the formation of the hydrogel nanocomplex was simulated and evaluated using the in silico methods. The results showed that after optimization of the structures by DMol3 based on DFT-D, the total energies of Nar, GP, CD, and ß-CD were calculated at -2100.159, -912.192, -3778.370, and -4273.078 Ha, respectively. The encapsulation energy of Nar on ß-CD in the solvent phase was calculated at -93.626 kcal/mol, and the Nar structure was located inside ß-CD in solution. The negative interaction energy value for the encapsulation of Nar on ß-CD suggests the exothermic adsorption process and a stable structure between Nar and ß-CD. Monte Carlo method was applied to obtain adsorption of CS/GP on Nar/ß-CD. Its value of the obtained interaction energy was calculated at -1.423 × 103 kcal/mol. The characterization confirmed the formation of a Nar/ß-CD inclusion complex. The Zeta potential of the pristine ß-CD changed from -4.60 ± 1.1 to -17.60 ± 2.34 mV after interaction with Nar, and the heightened surface negativity can be attributed to the existence of electron-rich naringin molecules, as well as the orientation of the hydroxyl (OH) group of the ß-CD toward the surface in an aqueous solution. The porosity of the fabricated hydrogels was in the range of 70-90% and during 14 days around 47.0 ± 3.1% of the pure hydrogel and around 56.4 ± 5.1 of hydrogel nanocomposite was degraded. The MTT assay showed that the hydrogels were biocompatible, and the wound contraction measurement (in an animal model) showed that the closure of the induced wound in the hydrogel nanocomposite treatment was faster than that of the control group (wound without treatment). The results of this study indicate that the developed bioactive wound healing 3D structure, which is composed of a chitosan hydrogel containing a Nar/ß-CD inclusion nanocomplex, has potential as an effective material for wound dressing applications.

Effectiveness of Platelet-Rich Plasma in the Treatment of Androgenic Alopecia: A Meta-Analysis.

BACKGROUND: Androgenetic alopecia (AGA) is a common yet difficult-to-treat condition, which is an important psychosocial problem. Platelet-rich plasma (PRP) therapy has been considered as a promising treatment for AGA. However, the current evidence on the efficacy of PRP for treating AGA is still controversial. This study evaluated the efficacy of PRP monotherapy in the treatment of AGA. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science to collect randomized controlled trials on use of PRP in AGA for a meta-analysis. RESULTS: Ten trials with a total 555 treatment units were identified. The hair density in PRP group was significantly higher than control group [MD = 25.09, 95%CI: 9.03-41.15, p = 0.002], but there was no significant difference in hair diameter between two groups [SMD = 0.57, 95%CI: - 0.23 to 1.38, p = 0.16]. Subgroup analyses indicated that hair density was significantly higher among the male-only trials than in the mixed-sex samples (p = 0.02). In addition, neither the split-head design nor the year of publication affected hair density (p = 0.05, p = 0.06). However, hair density was significantly higher in trials with a sample size less than 30 (p = 0.0004). CONCLUSIONS: PRP treatment increased hair density in participants with AGA, but not hair diameter. In terms of hair density, PRP elicits stronger effects in male patients. There was a trend toward differed treatment effect by gender with PRP injection, which warrants further investigation. Especially in the case of female. LEVEL OF EVIDENCE III: 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 https://www.springer.com/00266 .

The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review.

Recently, mesenchymal stromal cells (MSCs) and also their exosome has become a game-changing tool in the context of tissue engineering and regenerative medicine. MSCs due to their competencies to establish skin cells, such as fibroblast and keratinocyte, and also their unique attribute to suppress inflammation in wound site has attracted increasing attention among scholars. In addition, MSC's other capabilities to induce angiogenesis as a result of secretion of pro-angiogenic factors accompanied with marked anti-fibrotic activities, which mainly mediated by the releases matrix metalloproteinase (MMPs), make them a rational and effective strategy to accelerate wound healing with a small scar. Since the chief healing properties of the MSCs depend on their paracrine effects, it appears that MSCs-derived exosomes also can be an alternative option to support wound healing and skin regeneration as an innovative cell-free approach. Such exosomes convey functional cargos (e.g., growth factor, cytokine, miRNA, etc.) from MSCs to target cells, thereby affecting the recipient skin cells' biological events, such as migration, proliferation, and also secretion of ECM components (e.g., collagen). The main superiorities of exosome therapy over parental MSCs are the diminished risk of tumor formation and also lower immunogenicity. Herein, we deliver an overview of recent in vivo reports rendering the therapeutic benefits of the MSCs-based therapies to ease skin wound healing, and so improving quality of life among patients suffering from such conditions.

p75NTR silencing inhibits proliferation, migration, and extracellular matrix deposition of hypertrophic scar fibroblasts by activating autophagy through inhibiting the PI3K/Akt/mTOR pathway.

Hypertrophic scar (HS) results from abnormal wound healing, accompanied by excessive hypercellularity, migration, and extracellular matrix (ECM) deposition. Autophagy dysregulation plays crucial roles during HS formation. The overexpressed p75 neurotrophin receptor (p75NTR) in injured skin tissue after wound healing becomes a factor aggravating scar. This study was designed to investigate the role of p75NTR and p75NTR-mediated autophagy in the process of HS. The results revealed that p75NTR expression was significantly upregulated while that of autophagy proteins was downregulated in cicatrix at 3 and 6 months after a burn, which was recovered at 12 months. p75NTR silencing inhibited proliferation, migration, and ECM deposition of hypertrophic scar fibroblasts (HSF), whereas p75NTR overexpression presented the opposite results. Silencing of p75NTR reduced the expression of PI3K/Akt/mTOR signaling molecules while enhancing that of autophagy proteins. Importantly, PI3K agonist (IGF-1) intervention notably decreased the levels of LC3B II/I and Beclin-1 and restored the inhibitory effects of p75NTR silencing on proliferation, migration, and ECM deposition of HSF. Concurrently, autophagy inhibitor 3-methyladenine (3-MA) treatment exhibited the same variation trends with IGF-1. Taken together, these findings demonstrated that p75NTR silencing inhibits proliferation, migration, and ECM deposition of HSF by activating autophagy by inhibiting the PI3K/Akt/mTOR pathway.

Novel circular RNA, hsa_circ_0025039 promotes cell growth, invasion and glucose metabolism in malignant melanoma via the miR-198/CDK4 axis.

Malignant melanoma, a tumor derived from melanocytes, shows severe drug resistance and prompt metastasis, causing a serious threat to human health. Circular RNAs (circRNAs) are widely expressed in mammals and have been indicated to play important roles in tumorigenesis. In the present study, we analyzed the variability of circRNAs in malignant melanoma by microarray and identified six differentially expressed circRNAs. In particular, we found that hsa_circ_0025039, which is formed by FOXM1 exons, is significantly upregulated in melanoma. In vitro, the knockdown of circ_0025039 inhibited cell proliferation, colony formation ability, invasion and glucose metabolism in melanoma cells. Additionally, we identified miR-198 as a direct target of hsa_circ_0025039. Furthermore, we demonstrated that hsa_circ_0025039 regulates CDK4 expression by sponging miR-198. In vivo study indicated that the silencing of hsa_circ_0025039 inhibits melanoma tumor formation and downregulates miR-198 and CDK4 expression. Taken together, our data showed that circ_0025039 promotes cell growth, invasion and glucose metabolism in malignant melanoma by sponging miR-198 and regulating CDK4.

Long non-coding RNA GAS5 inhibits tumorigenesis via miR-137 in melanoma.

Melanoma is the leading cause of death in patients with skin cancer. In the present study, we aimed to prove the functions and molecular mechanisms of lncRNA-GAS5 in melanoma. Herein, we found that the expression of GAS5 was down-regulated in melanoma tissues compared to adjacent normal tissues. GAS5 was significantly associated with distal metastasis and TNM stage in melanoma. Furthermore, we found that GAS5 suppressed melanoma cell proliferation, migration and invasion. Then, we found thatmiR-137 was decreased in melanoma tissues compared to adjacent normal tissues and was correlated with GAS5. Using a luciferase reporter gene assay, we also demonstrated that GAS5 positively regulated miR-137 transcription. Finally, we suggested that GAS5 inhibited the growth of melanoma through miR-137 in vivo. Therefore, our research demonstrated that the GAS5/miR-137 axis could be a potential therapeutic target for the treatment of melanoma.

The long non-coding RNA NKILA inhibits the invasion-metastasis cascade of malignant melanoma via the regulation of NF-ĸB.

The long non-coding RNA (lncRNA) NKILA has been reported to participate in the development of human cancers. The purpose of this study was to explore the potential role of lncRNA-NKILA, which acts through NF-ĸB, in the process of melanoma development. Real-time PCR (qRT-PCR) showed that NKILA was expressed at low levels in human melanoma tissues. The area under the ROC curve of NKILA was 0.875, which indicated that NKILA may be a potential diagnostic biomarker of melanoma. Our results also indicated that NKILA inhibited the progression of cell proliferation, migration, and invasion, and promoted apoptosis of melanoma cells. Furthermore, qRT-PCR showed that NF-κB, which was negatively correlated with NKILA, was highly expressed in human melanoma tissues. Moreover, our results indicated that NKILA inhibited the carcinogenesis of melanoma cells through the inhibition of NF-ĸB in vitro. More importantly, we found that NKILA suppressed the growth of melanoma tumors via NF-ĸB in vivo. In conclusion, NKILA suppressed the development of malignant melanoma via the regulation of NF-ĸB and may be a potential therapeutic target in patients with melanoma.

Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma.

Cancer stem cells (CSCs) in most human tumors are commonly identified and enriched using similar strategies for identifying normal stem cells, including flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH) activity, and CD133 positivity. Thus, development of a method for isolating a specific cancer using cancer-specific characteristic appears to be potentially important. Here, we reported extremely high Lgr5 levels in the specimen from skin squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected high Lgr5 and CD133 levels in ALDH-high or side population from these cancer cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431 cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4-OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP-positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5-negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH-low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5-positive cells can be regenerated from Lgr5-negative cells. Furthermore, the growth of tA431 cells significantly decreased upon a single dose of diphtheria toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin SCC.