Adipose stem cell­derived exosomes promote high glucose-induced wound healing by regulating the TRIM32/STING axis.

Refractory diabetic wounds are still a clinical challenge that can cause persistent inflammation and delayed healing. Exosomes of adipose stem cells (ADSC-exos) are the potential strategy for wound repair; however, underlying mechanisms remain mysterious. In this study, we isolated ADSC-exos and identified their characterization. High glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) to establish in vitro model. The biological behaviors were analyzed by Transwell, wound healing, and tube formation assays. The underlying mechanisms were analyzed using quantitative real-time PCR, co-immunoprecipitation (Co-IP), IP, and western blot. The results showed that ADSC-exos promoted HG-inhibited cell migration and angiogenesis. In addition, ADSC-exos increased the levels of TRIM32 in HG-treated HUVECs, which promoted the ubiquitination of STING and downregulated STING protein levels. Rescue experiments affirmed that ADSC-exos promoted migration and angiogenesis of HG-treated HUVECs by regulating the TRIM32/STING axis. In conclusion, ADSC-exos increased the levels of TRIM32, which interacted with STING and promoted its ubiquitination, downregulating STING levels, thus promoting migration and angiogenesis of HG-treated HUVECs. The findings suggested that ADSC-exos could promote diabetic wound healing and demonstrated a new mechanism of ADSC-exos.

Multi-omics analysis of a case of congenital microtia reveals aldob and oxidative stress associated with microtia etiology.

BACKGROUND: Microtia is reported to be one of the most common congenital craniofacial malformations. Due to the complex etiology and the ethical barrier of embryonic study, the precise mechanisms of microtia remain unclear. Here we report a rare case of microtia with costal chondrodysplasia based on bioinformatics analysis and further verifications on other sporadic microtia patients. RESULTS: One hundred fourteen deleterious insert and deletion (InDel) and 646 deleterious SNPs were screened out by WES, candidate genes were ranked in descending order according to their relative impact with microtia. Label-free proteomic analysis showed that proteins significantly different between the groups were related with oxidative stress and energy metabolism. By real-time PCR and immunohistochemistry, we further verified the candidate genes between other sporadic microtia and normal ear chondrocytes, which showed threonine aspartase, cadherin-13, aldolase B and adiponectin were significantly upregulated in mRNA levels but were significantly lower in protein levels. ROS detection and mitochondrial membrane potential (∆ Ψ m) detection proved that oxidative stress exists in microtia chondrocytes. CONCLUSIONS: Our results not only spot new candidate genes by WES and label-free proteomics, but also speculate for the first time that metabolism and oxidative stress may disturb cartilage development and this might become therapeutic targets and potential biomarkers with clinical usefulness in the future.

Treatment of Progressive Hemifacial Atrophy by Cartilage Graft and Free Adipofascial Flap Combined with Three-Dimensional Planning.

BACKGROUND: Progressive hemifacial atrophy (PHA) is a rare disease characterized by progressive atrophy of skin, soft tissue, muscles, and underlying bone structures. For severe PHA patients with obvious bone deformities, skeletal framework reconstruction is needed in addition to soft-tissue augmentation. The authors propose a new combinatorial surgical method using rib cartilage graft and free adipofascial flap for restoring facial symmetry. To improve the surgical accuracy, preoperative three-dimensional planning and printing was used. METHODS: Twelve patients with severe facial atrophy were included in the authors' study. Three-dimensional facial image analyses were performed preoperatively to quantify the facial asymmetry. Rib cartilages were harvested and sculptured to the appropriate shape created by three-dimensional planning and fixed to the atrophic bone. The circumflex scapular artery-based adipofascial flap was transplanted to repair soft-tissue deficiency. A residual small monitor flap was left with the adipofascial flap. A revision surgery was performed to perfect the repair if the contour was suboptimal 6 months postoperatively. RESULTS: The adipofascial flaps survived in all 12 patients. All patients achieved good healing without complications. At 1 more year after surgery, the rib cartilage was still in position and rarely absorbed. The morphologic and volumetric difference between the affected side and the unaffected side was improved significantly postoperatively. All patients were satisfied with the results, and no more additional operations were required. CONCLUSION: The combinatorial surgery of rib cartilage graft and free adipofascial flap in the setting of three-dimensional planning and printing can be a good choice in restoring facial symmetry in severe cases of PHA. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Long-term Safety and Effectiveness of Hyaluronic Acid Fillers Correcting Nasolabial Folds in Chinese Patients.

Background: Soft-tissue fillers, specifically hyaluronic acid fillers, can reduce many signs of aging by treating the associated loss of subcutaneous fat and midfacial contour deficiencies. The objective of this study was to investigate whether the effectiveness and safety of Belotero Volume Lidocaine (BVL) compared with Restylane (RES, control) is noninferior in the treatment of severe nasolabial folds (NLFs) in Chinese patients. Methods: This was a prospective, randomized, controlled, split-face clinical study. Overall, 220 Chinese patients of both sexes with symmetrical NLFs of severe intensity (grade 4) on the Wrinkle Severity Rating Scale (WSRS) were treated with both fillers. Treatment outcomes were assessed by the WSRS, and other scales, at multiple time points up to 18 months postinjection. The co-primary effectiveness outcomes were based on the blinded evaluator ratings of NLFs according to the WSRS scale after 6 and 12 months. Adverse events were assessed during the whole study and patients' pain sensation at three time points after injection. Results: Noninferiority of BVL versus control based on the WSRS was demonstrated at month 6 and month 12. Response rates were slightly higher for BVL than control at all time points, and BVL had a sustained effect until month 18. Pain sensation scores were significantly lower for BVL compared with control. The incidence rates of treatment-related AEs were low and very similar for both treatments. Conclusions: This study demonstrates that BVL is a safe, long-lasting, and effective treatment to correct severe NLFs in Chinese patients while being noninferior to the control device.

Keloid Core Factor CTRP3 Overexpression Significantly Controlled TGF-ß1-Induced Propagation and Migration in Keloid Fibroblasts.

Purpose: Keloid is a type of benign fibrous proliferative tumor characterized by excessive scarring. C1q/TNF-related protein 3 (CTRP3) has been proven to possess antifibrotic effect. Here, we explored the role of CTRP3 in keloid. In the current research, we examined the influence of CTRP3 on keloid fibroblasts (KFs) and investigated the potential molecular mechanism. Methods: KF tissue specimens and adjacent normal fibroblast (NF) tissues were collected cultured from 10 keloid participants. For the TGF-ß1 stimulation group, KFs were processed with human recombinant TGF-ß1. Cell transfection of pcDNA3.1-CTRP3 or pcDNA3.1 was performed. The siRNA of CTRP3 (si-CTRP3) or negative control siRNA (si-scramble) was transfected into KFs. Results: CTRP3 was downregulated in keloid tissues and KFs. CTRP3 overexpression significantly controlled TGF-ß1-induced propagation and migration in KFs. Col I, α-SMA, and fibronectin mRNA and protein levels were enhanced by TGF-ß1 stimulation, whereas they were inhibited by CTRP3 overexpression. In contrast, CTRP3 knockdown exhibited the opposite effect. In addition, CTRP3 attenuated TGF-ß receptors TRI and TRII in TGF-ß1-induced KFs. Furthermore, CTRP3 prevented TGF-ß1-stimulated nuclear translocation of smad2 and smad3 and suppressed the expression levels of p-smad2 and p-smad3 in KFs. Conclusion: CTRP3 exerted an antifibrotic role through inhibiting proliferation, migration, and ECM accumulation of KFs via regulating TGF-ß1/Smad signal path.

Application Effect of Silver-Containing Dressings in the Repair of Chronic Refractory Wounds.

Chronic refractory wounds have complicated pathogenesis, repeatedly prolonged course of disease, high difficulty in cure, and may even endanger life due to the spread of wound infection. Silver ion dressing is a new type of dressing applied clinically in recent years. It can prevent infection and promote wound healing by releasing a low level of active silver ions into wound fluid or secretion. Some scholars have found that silver ion dressings can promote the healing of refractory wounds. In this study, 80 cases of chronic refractory wounds treated in our department from June 2019 to January 2022 were selected as the research subjects and the effect of silver ion dressing coverage on the repair of chronic refractory wounds after debridement was explored.

Circular RNA_0061587 is associated with the tumorigenesis of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a kind of common neurogenetic disorder associated with various developmental deficits. Circular RNAs (circRNAs) have been frequently verified to be crucial modulators in human diseases. However, the functions of circRNAs on the occurrence of NF1 remain largely obscure. In our study, RT-qPCR was applied to analyze circ_0061,587 expression and we noticed that circ_0061,587 expression was overtly elevated in human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cell lines. Meanwhile, the results of loss-of-function assays revealed that silencing of circ_0061,587 hampered the proliferation, migration, and invasion but stimulated the apoptosis of human NF1-associated MPNST cells. In addition, mechanism assays were implemented to unveil the possible regulatory mechanism behind circ_0061,587. As a result, circ_0061,587 sequestered microRNA-485-5p (miR-485-5p) to modulate the expression of RUNX family transcription factor 1 (RUNX1) and annexin A11 (ANXA11). Finally, rescue experiments confirmed that circ_0061,587 boosted the malignant behaviors of human NF1-associated MPNST cells through up-regulating RUNX1 and ANXA11. In conclusion, circ_0061,587 functioned as an oncogene in NF1-associated MPNST cells and this study might provide novel insights for the diagnosis and treatment of NF1.

Environmentally Compatible Wearable Electronics Based on Ionically Conductive Organohydrogels for Health Monitoring with Thermal Compatibility, Anti-Dehydration, and Underwater Adhesion.

Hydrogel-based electronics have found widespread applications in soft sensing and health monitoring because of their remarkable biocompatibility and mechanical features similar to human skin. However, they are subjected to potential challenges like structural failure, functional degradation, and device delamination in practical applications, especially facing extreme environmental conditions (e.g., abnormal temperature and humidity). To address these, ionically conductive organohydrogel-based soft electronics are developed, which can perform at subzero and elevated temperatures (thermal compatibility) as well as at dehydrated and hydrated environments (hydration compatibility) for extended applications. More specifically, gelatin/poly(acrylic acid-N-hydrosuccinimide ester) (PAA-NHS ester)-based ionic-conductive organohydrogel is synthesized. By introducing a glycerol-water binary solvent system, the gel can maintain mechanical softness in a wide temperature range (from -80 to 60 °C). Besides, excellent conductivity is achieved under various conditions by soaking the gel into lithium chloride anhydrous (LiCl) solution. Strong adhesion with skin, even under water, can be realized by covalent bonds between NHS ester from gel and amino groups from human skin. The excellent performances of LiCl-loaded PAA-based organohydrogel (L-PAA-OH)-based electronics are further demonstrated under freezing and high temperatures as well as underwater conditions, unveiling their promising prospects in wearable health monitoring in various conditions.

Exosomes from adipose-derived mesenchymal stem cells promote survival of fat grafts by regulating macrophage polarization via let-7c.

The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years. Owing to their anti-inflammatory effects and regenerative property, adipose-derived mesenchymal stem cells (AD-MSCs) have been adapted for clinical application in fat grafting, although the mechanism underlying their action remains unclear. Recently, exosomes derived from MSCs were suggested as a better alternative, and these exosomes have also been applied in diverse clinical therapies. Accumulating evidence suggests that MSCs modulate macrophage differentiation via exosome secretion, and the connection between macrophage regulation and the rate of fat graft survival has been established. Here, we identified that let-7c, the key factor in the regulatory process, is shuttled by AD-MSC-derived exosomes to downregulate the transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ. The downregulation of C/EBP-δ resulted in the attenuation of pro-inflammatory M1 macrophages and elevation of anti-inflammatory M2 macrophages. These results suggest that AD-MSC-derived exosomes promote the survival of fat grafts by regulating macrophage polarization via let-7c. This is the first study to elucidate the mechanism underlying the promotion of the fat graft survival rate by AD-MSCs and to evaluate the immunotherapeutic potential of AD-MSC-derived exosomes in fat grafting.

Modified Buried Vertical Mattress Suture Versus Buried Intradermal Suture: A Prospective Split-Scar Study.

BACKGROUND: The modified buried vertical mattress suture (MBVMS) is believed to provide excellent outcomes by relieving the tension on wound edges. However, clinical data on the topic remain sparse and inadequate. OBJECTIVE: To compare the cosmetic results of the MBVMS and the buried intradermal suture (BIS) in chest wounds using a split-scar model. MATERIALS AND METHODS: Twenty patients participated in the study. One randomly selected half of each chest wound was closed with the MBVMS; the other half was closed with the BIS. Immediately, postoperatively, the maximum degree of wound eversion was obtained. After 3 months, the wound complication rates were recorded, and the aesthetic appearance of each scar was evaluated by the Patient and Observer Scar Assessment Scale (POSAS), the Vancouver Scar Scale (VSS), the visual analog scale (VAS), and scar width. RESULTS: The MBVMS yielded a greater mean postoperative eversion height and width (p < .05); lower POSAS, VSS, and VAS scores (p < .05); and a narrower scar width (p < .05) than did the BIS. CONCLUSION: Compared with the BIS, the MBVMS provided significantly increased wound eversion immediately, postoperatively, and improved aesthetic outcomes at the end of the 3-month follow-up period.

Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF­ß1.

Cutaneous neurofibromas (cNFs) are present in the majority of patients with neurofibromatosis type 1 (NF1), and results in disfigurements of the body, which is associated with psychological distress. A hallmark feature of cNF is the infiltration of inflammatory cells, among which macrophages are an important component of the microenvironment. Loss of neurofibromin (Nf1) expression results in activation of the PI3K and MAPK signaling pathways; however, the therapeutic effects of specific inhibitors targeting these pathways are not satisfactory. The present study showed increased macrophage infiltration accompanied by activation of effectors of the Hippo signaling pathway. Additionally, it was shown that XMU­MP­1 enhanced macrophage accumulation, in vivo and in vitro, by elevating the levels of C­C motif chemokine ligand 5 (CCL5) and transforming growth factor (TGF)­ß1 expression. However, neither CCL5 nor TGF­ß1 ablation alone were able to effectively reverse the XMU­MP­1­induced upregulation of macrophage accumulation, whereas concurrent ablation of these two genes significantly decreased macrophage accumulation. EdU staining and flow cytometry suggested that activated Yes­associated protein 1 promoted proliferation rather than inhibiting apoptosis in macrophage cells, and this may underlie the increase in the accumulation of macrophages. Both CCL5/C­C motif chemokine receptor 5 and TGF­ß1/TGFß1 receptor served crucial roles in modulating macrophage proliferation, which ultimately contributed to macrophage accumulation. The function of the Hippo pathway in the development of cNF development and its potency as a therapeutic target merit further investigation.

ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/ß-catenin pathway.

Cutaneous wound is a soft tissue injury that is difficult to heal during aging. It has been demonstrated that adipose-derived stem cells (ADSCs) and its secreted exosomes exert crucial functions in cutaneous wound healing. The present study aimed to elucidate the mechanism of exosomes derived from ADSCs (ADSC-Exos) containing MALAT1 in wound healing. ADSCs were isolated from human normal subcutaneous adipose tissues and identified by flow cytometry analysis. Exosomes were extracted from ADSC supernatants and MALAT1 expression was determined using qRT-PCR analysis. HaCaT and HDF cells were exposed to hydrogen peroxide (H2O2) for simulating the skin lesion model. Subsequently, CCK-8, flow cytometry, wound healing and transwell assays were employed to validate the role of ADSC-Exos containing MALAT1 in the skin lesion model. Besides, cells were transfected with sh-MALAT1 to verify the protective role of MALAT1 in wound healing. The binding relationship between MALAT1 and miR-124 were measured by dual-luciferase reporter assay. ADSC-Exos promoted cell proliferation, migration, and inhibited cell apoptosis of HaCaT and HDF cells impaired by H2O2. However, the depletion of MALAT1 in ADSC-Exos lose these protective effects on HaCaT and HDF cells. Moreover, miR-124 was identified to be a target of MALAT1. Furthermore, ADSC-Exos containing MALAT1 could mediate H2O2-induced wound healing by targeting miR-124 and activating Wnt/ß-catenin pathway. ADSC-Exos containing MALAT1 play a positive role in cutaneous wound healing possibly via targeting miR-124 through activating the Wnt/ß-catenin pathway, which may provide novel insights into the therapeutic target for cutaneous wound healing.

Infiltrating Macrophages Induced Stem-cell-like Features Through PI3K/AKT/GSK3ß Signaling to Promote Neurofibroma Growth.

BACKGROUND: Inflammation plays an important role in promoting neurofibroma progression, and macrophages are key inflammatory cells in neurofibroma. AIM OF THIS STUDY: We attempted to clarify the detailed mechanism of infiltrating macrophages promoting neurofibroma progression. METHODS: We performed IHC and Western blot assays to detect the expression levels of OCT3/4, Nanog and SOX2 in tissues and cells. A colony/sphere formation assay was used to analyze cell stemness. MTT, colony formation assay and xenograft tumor model were used to detect cell growth. The transwell system was used to examine macrophage infiltration. RESULTS: We demonstrated increased macrophage infiltration in neurofibroma tissues accompanied by increased stem cell-like markers. Moreover, Nf1-mutated SW10 cells possessed a stronger capacity to recruit macrophages, which in turn facilitated neurofibroma growth. Mechanistically, the infiltrating macrophages induced neurofibroma cell stem cell transition by modulating PI3K/AKT/GSK3ß signaling, which then enhanced neurofibroma cell viability in vivo and in vitro. CONCLUSION: Our results revealed a new mechanism of infiltrating macrophages contributing to neurofibroma progression, and targeting this newly identified signaling may help to treat neurofibroma.

AR facilitates YAP-TEAD interaction with the AM promoter to enhance mast cell infiltration into cutaneous neurofibroma.

Abundant mast cell infiltration and disease initiation at puberty are hallmark features of cutaneous neurofibroma (cNF). However, the association between mast cell infiltration and steroid hormones in cNF remains unclear. Here, we determined that androgen receptor (AR) expression is positively associated with mast cell density in cNF tissues. Moreover, both in vitro cell experiments and in vivo mouse models verified that activated AR promoted mast cell infiltration and that AR inhibition reduced mast cell infiltration. Analyses in cell models and xenograft tumours both demonstrated that AR upregulated Yes associate  protein 1 (YAP)-adrenomedullin (AM) signalling. Clinical samples from cNF patients further verified that AR was positively related to YAP and AM. Mechanistic analysis revealed that AR accelerates AM transcription via enhancing YAP- TEA domain transcription factor (TEAD) binding to the AM promoter. Consequently, the upregulated AM enhanced mast cell recruitment. Interruption of the YAP-TEAD interaction or inhibition of AM could impair mast cell accumulation induced by active AR, which indicated that this newly found signalling pathway may provide novel targets for cNF treatment.

Activation of PLCγ/AKT/IκBα/p65 signaling increases inflammation in mast cells to promote growth of cutaneous neurofibroma.

AIM: Cutaneous neurofibroma (cNF), a hallmark feature of neurofibromatosis type 1 (NF1), results in psychological and physical damage to patients. Considering the important role of mast cells in neurofibroma development, the aim of this study was to elucidate the underlying mechanism of the interaction between cNF cells and mast cells. MAIN METHODS: SW10 cells with Nf1 knocked down were used as a cNF cell model. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays, as well as a mouse xenograft tumor model, were used to assess the cNF tumor growth in vivo and in vitro. ELISAs and IHC were used to examine the inflammatory activity of mast cells. KEY FINDINGS: We demonstrated that cNF cells activated mast cells, which in turn promoted the cNF cell growth, while suppression of the inflammatory activity of cNF-associated mast cells reversed their stimulating effect on the growth of cNF cells. Mechanistic studies revealed that SW10 cells upregulated PLCγ/AKT/IκBα/p65 signaling in mast cells, thereby increasing inflammation. Moreover, PLCγ modulated the AKT/IκBα/p65 signaling activity and played a critical role in the interaction of mast cells and cNF cells. Knockdown of PLCγ in mast cells diminished their cNF cell-induced inflammatory activity and subsequently reduced the cNF cell growth in vivo and in vitro. SIGNIFICANCE: This study revealed a novel interaction between mast cells and cNF cells, suggesting a potential strategy for treating cNF by targeting the newly recognized signaling pathway.

Tailored Microform Cleft Lip Repair: Personalizing Small Incisions, Orbicularis Reconstruction, and Rhinoplasty.

BACKGROUND: In the last decade, many surgeons have reported their perspectives on microform cleft lip repair, including techniques for incision placement and size, philtral reconstruction, and nasal base reconstruction. This interest demonstrates continued controversy in the repair of microform cleft lip. METHODS: This is a retrospective cohort of patients from 2010 to 2016. The authors included patients with microform cleft lip repaired by our described technique who had both preoperative photographs, as well as photographs taken at >1-year follow-up. Patient outcomes were assessed through anthropometric measurements and also subjectively by 3 senior residents of plastic surgery. RESULTS: The inclusion criteria yielded 36 microform cleft lip patients. Most patients were satisfied with their results. Regarding subjective assessment, the scar appearance and symmetry was fairly good. Objective measurements indicated excellent symmetry, with the cleft side achieving 92.58% of the height and measurements of the non-cleft side. CONCLUSIONS: Our method of combining labial muscle reconstruction through a personalized, small incision effectively corrects microform cleft lip deformity with minimal scar burden.

Activated androgen receptor accelerates angiogenesis in cutaneous neurofibroma by regulating VEGFA transcription.

Accumulating evidence has demonstrated the significant progression of cutaneous neurofibroma (cNF) without necrosis during puberty. However, the molecular events involved in this process remain unclear. The alteration of the steroid hormone levels during puberty has led to the investigation of the expression levels of the androgen receptor (AR). A positive correlation between AR expression and microvessel density has been reported in human cNF tissues in combination with enhanced endothelial cell tube formation in vitro. In addition, activated AR signaling can promote neurofibroma cell growth in vivo and in vitro and tube formation in vitro. In the present study, AR was shown to bind directly to the promoter of vascular endothelial growth factor A (VEGFA), a key factor involved in angiogenesis, and to sequentially induce its expression. Furthermore, the AR inhibitor, MDV3100, downregulated VEGFA expression and abolished endothelial cell recruitment and tube formation. Taken collectively, the findings of this study revealed that AR signaling enhanced tumor growth and angiogenesis in cNF by regulating VEGFA transcription. However, whether AR can be regarded a therapeutic target for cNF requires further investigation.

Different suturing techniques in thoracic incision: protocol for a feasibility randomised controlled trial.

INTRODUCTION: Based on the principles of the ideal skin closure technique, we previously described a suture technique (wedge-shaped excision and modified buried vertical mattress suture (WE-MBVMS)) that could provide excellent outcomes for the most demanding surfaces. However, adequate clinical comparative evidence supporting improved outcomes is lacking. Thus, the purpose of this protocol is to establish the feasibility of conducting a fully randomised controlled trial (RCT) comparing the clinical effectiveness of WE-MBVMS with a buried intradermal suture (BIS) in closing thoracic incision. METHODS AND ANALYSIS: This study is a feasibility RCT of WE-MBVMS and BIS in patients undergoing surgery for costal cartilage harvesting. Seventy-eight participants are expected to participate in the study and will be randomised in a ratio of 1:1 to WE-MBVMS or BIS. Trial feasibility will be assessed by the number of participants assessed for eligibility, recruitment rates, reasons for ineligibility or non-participation, time for interventions, withdrawal and retention at all follow-up points (3, 6 and 12 months), follow-up rates and reasons for withdrawing from the trial. In addition, clinical data regarding the cosmetic results of scars will be collected to inform the sample size for a fully powered RCT. ETHICS AND DISSEMINATION: This study has been approved by The First Affiliated Hospital of Xi'an Jiaotong University Institutional Review Board (XJTU1AF2017LSK-120). The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013335; Pre-results.

Antioxidative and antiphotoaging activities of neferine upon UV-A irradiation in human dermal fibroblasts.

Our daily exposure to ultraviolet radiation (UVR) results in the production of reactive oxygen species (ROS), lipids, proteins and DNA damage and alteration in fibroblast structure, thus contributing to skin photoaging. For this reason, the use of natural bioactive compounds with antioxidant activity could be a strategic tool to overcome ultraviolet A (UV-A) induced deleterious effect. Neferine is an alkaloid extract from the seed embryos of lotus (Nelumbo nucifera Gaertn). In the present study, we report the protective effect of neferine against UV-A induced oxidative stress and photoaging in human dermal fibroblasts (HDFs). HDFs subjected to UV-A irradiation showed increased production of ROS and malondialdehyde (MDA). Furthermore, it depleted the cellular enzymatic antioxidant superoxide dismutase (SOD) and non-enzymatic antioxidant glutathione peroxidase (GPx). On the other hand, HDFs treated with neferine followed by UV-A irradiation reversed the process, reduced the ROS and lipid peroxidation and restored the antioxidants pool. Moreover, neferine treatment significantly inhibited UV-A induced matrix metalloproteinase-1 (MMP-1) expression in HDFs. Remarkable morphological and ultrastructural alterations observed in HDFs upon UV-A irradiation, were also reduced with neferine treatment. Taken together, our results suggest that neferine has strong antioxidative and photoprotective properties and thus may be a potential agent for the prevention and treatment of UV-A mediated skin photoaging.

[The development and recent status of the craniomaxillofacial surgery in China during past three decades].

The authors made a profound review on the development and the recent status of craniomaxillofacial surgery in China during past three decades. The emphases were placed on the following aspects: the modifications of the reconstructive procedure and minimal invasive mode, the researches on molecular genetic characteristics of the congenital craniofacial malformations, the clinical applications of three-dimensional digital computer-aided techniques (including three-dimensional printing and prefabricated template for precious osteotomies), the craniomaxillofacial defects reconstructing by using the distraction osteogenesis and osseous integrated titanium implant and prothesis, etc. Finally, the authors outlooked prospectively the future trends of the craniomaxillofacial surgery.