Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing.

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.

ASH2L Mediates Epidermal Differentiation and Hair Follicle Morphogenesis through H3K4me3 Modification.

The processes of epidermal development in mammals are regulated by complex molecular mechanisms, such as histone modifications. Histone H3 lysine K4 methylation mediated by COMPASS (complex of proteins associated with Set1) methyltransferase is associated with gene activation, but its effect on epidermal lineage development remains unclear. Therefore, we constructed a mouse model of specific ASH2L (COMPASS methyltransferase core subunit) deletion in epidermal progenitor cells and investigated its effect on the development of mouse epidermal lineage. Furthermore, downstream target genes regulated by H3K4me3 were screened using RNA sequencing combined with Cleavage Under Targets and Tagmentation sequencing. Deletion of ASH2L in epidermal progenitor cells caused thinning of the suprabasal layer of the epidermis and delayed hair follicle morphogenesis in newborn mice. These phenotypes may be related to the reduced proliferative capacity of epidermal and hair follicle progenitor cells. ASH2L depletion may also lead to depletion of the epidermal stem cell pools in late mouse development. Finally, genes related to hair follicle development (Shh, Edar, and Fzd6), Notch signaling pathway (Notch2, Notch3, Hes5, and Nrarp), and ΔNp63 were identified as downstream target genes regulated by H3K4me3. Collectively, ASH2L-dependent H3K4me3 modification served as an upstream epigenetic regulator in epidermal differentiation and hair follicle morphogenesis in mice.

KIF4A functions as a diagnostic and prognostic biomarker and regulates tumor immune microenvironment in skin cutaneous melanoma.

BACKGROUND: KIF4A is upregulated in various malignancies and serves as an independent risk factor. However, its function in skin cutaneous melanoma (SKCM) and the regulation of the immunological environment remains unknown. METHODS: We first explored the mRNA and protein levels of KIF4A in SKCM through public databases. Then, the co-expressed genes with KIF4A in SKCM and their functional enrichment analysis were performed. Moreover, the clinical value, relationship with immune infiltration and tumor microenvironment (TME), as well as the correlation between KIF4A and immunomodulators were evaluated. In addition, we validated the function of KIF4A by in vitro experiments such as CCK-8 assay, clone formation and wound healing assay. RESULTS: Our data reveal that the mRNA and protein levels of KIF4A are highly expressed in SKCM. Moreover, functional enrichment analysis of the top 50 co-expressed genes with KIF4A showed significant association with organelle fission, tubulin binding and immune processes. KIF4A can distinguish SKCM from normal tissue and predict a poorer prognosis. A negative association was observed between KIF4A and TME, and KIF4A exhibited a negative correlation with most immunomodulators. Additionally, the knockdown of KIF4A inhibited the proliferation and migration ability of A375 cells. CONCLUSIONS: Our findings suggest that KIF4A promotes the progression of SKCM and is negatively associated with immune infiltration and immunomodulators, which indicates a poor prognosis.

Weighted gene co-expression network analysis and machine learning identified the lipid metabolism-related gene LGMN as a novel biomarker for keloid.

The aetiology of keloid formation remains unclear, and existing treatment modalities have not definitively established a successful approach. Therefore, it is necessary to identify reliable and novel keloid biomarkers as potential targets for therapeutic interventions. In this study, we performed differential expression analysis and functional enrichment analysis on the keloid related datasets, and found that multiple metabolism-related pathways were associated with keloid formation. Subsequently, the differentially expressed genes (DEGs) were intersected with the results of weighted gene co-expression network analysis (WGCNA) and the lipid metabolism-related genes (LMGs). Then, three learning machine algorithms (SVM-RFE, LASSO and Random Forest) together identified legumain (LGMN) as the most critical LMGs. LGMN was overexpressed in keloid and had a high diagnostic performance. The protein-protein interaction (PPI) network related to LGMN was constructed by GeneMANIA database. Functional analysis of indicated PPI network was involved in multiple immune response-related biological processes. Furthermore, immune infiltration analysis was conducted using the CIBERSORT method. M2-type macrophages were highly infiltrated in keloid tissues and were found to be significantly and positively correlated with LGMN expression. Gene set variation analysis (GSVA) indicated that LGMN may be related to promoting fibroblast proliferation and inhibiting their apoptosis. Moreover, eight potential drug candidates for keloid treatment were predicted by the DSigDB database. Western blot, qRT-PCR and immunohistochemistry staining results confirmed that LGMN was highly expressed in keloid. Collectively, our findings may identify a new biomarker and therapeutic target for keloid and contribute to the understanding of the potential pathogenesis of keloid.

Shear Wave Elastography for Assessment of Changes in Abdominal Soft Tissues after Lipoabdominoplasty.

BACKGROUND: The changes in the elasticity of the abdominal skin, subcutaneous tissues and muscles after lipoabdominoplasty are still unknown. The aim of this study was to provide an objective assessment of tissue elasticity after lipoabdominoplasty using ultrasound elastography. METHODS: A total of 21 female patients (31-41 years old) who underwent lipoabdominoplasty from Oct 2019 to Mar 2022 were included in this retrospective study. The elastography values of the skin, subcutaneous tissues and abdominal muscles were obtained with the ultrasound shear wave elasticity imaging system pre-operation (Pre) and 6 months post-operation (Post) at four different points. RESULTS: Twenty-one female patients were included. The elasticity of the abdominal skin, subcutaneous tissues, rectus abdominis and external oblique abdominis significantly increased at 6 months post-operation. The improvements in abdominal soft tissue elasticity were not uniform across the examined points. CONCLUSIONS: Significant changes in the elasticity of the abdominal skin, subcutaneous tissues and muscles were observed after lipoabdominoplasty. Ultrasound elastographic assessment was objective and feasible for evaluating the effect of lipoabdominoplasty on abdominal soft tissue. 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 www.springer.com/00266 .

[Research progress on the role and clinical application of Siglecs in tumor immunity].

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.

METTL14-mediated N6-methyladenosine modification of Col17a1/Itgα6/Itgß4 governs epidermal homeostasis.

BACKGROUND: N6-methyladenosine (m6A) is the most abundant and reversible modification occurring in eukaryotic mRNAs, however, its functions in mammalian epidermal development are still not fully elucidated. OBJECTIVE: To explore the role of METTL14 (Methyltransferase like 14), one of the m6A methyltransferases, in maintaining epidermal homeostasis. METHODS: We constructed mice with Mettl14-inactivation in the epidermal basal cells. The phenotype was explored by H&E staining and immunofluorescence staining. To explore the underlying mechanisms, we performed RNA-seq, Ribosome profiling and MeRIP-seq on wild-type and Mettl14-inactivation epidermal keratinocytes. Moreover, HaCaT cells were used for in vitro validation. RESULTS: Inactivation of Mettl14 in murine epidermis led to transient thicker epidermis and exhaustion of the epidermal stem cell pool. Interestingly, we found that the mRNA of type XVII collagen (Col17a1), integrin ß4 (Itgß4) and α6 (Itgα6) had m6A modifications, and the proteins expression were decreased in Mettl14-inactivated epidermis. Furthermore, in epidermis-specific Mettl4-inactivated mice, the epidermis was detached from the dermis and presented a phenotype similar to junctional epidermolysis bullosa (JEB), which may result from hemidesmosomes damage (decrease of COL17A1, ITGB4 and ITGA6). Knockdown of Mettl14 in HaCaT cells impaired the self-renewal and decreased the protein level of COL17A1, ITGB4 and ITGA6 and Itgß4 knockdown inhibited colony formation. CONCLUSION: Our study highlighted the role of METTL14 in the maintenance of epidermal homeostasis and identified its critical role through m6A-mediated translational inhibition of Col17a1, Itgß4 and Itgα6. Our study suggested that METTL14 may be a potential therapeutic target for the treatment of hemidesmosomes-deficient diseases, such as JEB.

Hybrid Autologous Costal Cartilage Grafting for Augmentation Rhinoplasty in Asian Patients.

BACKGROUND: Autologous costal cartilage has been used for augmentation rhinoplasty in Asia for many years. This study aimed to assess the effectiveness and safety of hybrid grafting of costal cartilage for dorsal augmentation, septal reconstruction, and tip augmentation for Asian patients. METHODS: A surgical technique was introduced and patients having rhinoplasty using this technique from April 2020 to March 2021 were retrospectively studied. In this technique, costal cartilage was meticulously carved or diced and grafted in various ways mainly based on the anatomic characteristics of nasal skin and subcutaneous soft tissues as well as bone and cartilage framework. The surgical outcomes, patient satisfaction, and complications retrieved from the documented medical records were reviewed and analyzed. RESULTS: Twenty-five patients having rhinoplasty with the proposed technique were followed up from 6 months to 12 months. As for cosmetic outcomes, 21 patients were graded as good, 3 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had over-rotated tips, insufficient dorsal augmentation, or asymmetry of nostrils and soft tissue contracture. The overall patient satisfaction was as high as 96.0%. Local infection occurred in 1 patient and hematoma was not observed. Warping and visibility of costal cartilage were not observed in any patients. Slight displacement of diced cartilages was found in 2 patients near the radix 1 week postoperatively. CONCLUSIONS: Hybrid autologous costal cartilage grafts can be used for both tip refinement and dorsal augmentation for East Asian patients and achieve an outcome of a natural-looking nose with minimal complications. LEVEL OF EVIDENCE: Level IV.

"Find-eat" strategy targeting endothelial cells via receptor functionalized apoptotic body nanovesicle.

Endothelial cell (EC) injury plays a key role in the chronic wound process. A long-term hypoxic microenvironment hinders the vascularization of ECs, thus delaying wound healing. In this study, CX3CL1-functionalized apoptotic body nanovesicles (nABs) were constructed. The "Find-eat" strategy was implemented through a receptor-ligand combination to target ECs that highly express CX3CR1 in the hypoxic microenvironment, therefore amplifying the "Find-eat" signal and promoting angiogenesis. Apoptotic bodies (ABs) were obtained by chemically inducing apoptosis of adipose-derived stem cells (ADSCs), and then functionalized nABs containing deferoxamine (DFO-nABs) were obtained through a series of steps, including optimized hypotonic treatment, mild ultrasound, drug mixing and extrusion treatment. In vitro experiments showed that nABs had good biocompatibility and an effective "Find-eat" signal via CX3CL1/CX3CR1 to induce ECs in the hypoxic microenvironment, thereby promoting cell proliferation, cell migration, and tube formation. In vivo experiments showed that nABs could promote the rapid closure of wounds, release the "Find-eat" signal to target ECs and realize the sustained release of angiogenic drugs to promote new blood vessel formation in diabetic wounds. These receptor-functionalized nABs, which can target ECs by releasing dual signals and achieve the sustained release of angiogenic drugs, may provide a novel strategy for chronic diabetic wound healing.

Association of novel MUC16, MAP3K15 and ABCA1 mutation with giant congenital melanocytic nevus.

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are generally lacking in the Chinese population. Mutated genes in this disease can estimate the risk of malignant transformation in GCMN. Therefore, it is worth investigating the genetic information of GCMN. METHODS: Here, we presented two cases of GCMN of the upper extremities. The clinical and histological data were analyzed. The whole exome sequencing (WES) was performed to investigate the mutational profile of peripheral venous blood (PB), normal skin (NS), small melanocytic nevus (SMN), deep penetrating and non-penetrating GCMN (dPGCMN and nPGCMN). RESULTS: We showed a reduction in the circumference of involved upper extremities in both patients. The clinical and histopathological data indicated the reduction of adipose tissue associated with the invasion of GCMN. The WES data revealed that MUC16, MAP3K15 and ABCA1 were novel potential candidate genes for the disease as well as biomarkers for predicting malignant transformation. CONCLUSION: The MUC16, MAP3K15 and ABCA1 may serve as novel biomarkers for predicting malignant transformation and targets for the diagnoses and therapy for the GCMN.

Stereoisomeric coordination polymers based on facial and meridional six-coordinate dysprosium(III ).

Due to the small differences in the chemical properties of facial (fac) and meridional (mer) stereoisomers, selective synthesis of one of the isomers is challenging, especially for lanthanide complexes. By using a flexible bidentate phosphine oxide ligand, we managed to isolate three stereoisomeric 2D and 3D coordination polymers, in which six-coordinate Dy(III) ions possess fac- or mer-Cl3O3 coordination environments. Structural studies indicate that the stereochemistry differences result from their various supramolecular interactions (e.g., hydrogen bonding and π⋯π stacking). Magnetic property measurements reveal the different static and dynamic magnetic behaviours of the three stereoisomers. Ab initio CASSCF calculations were then performed which indicated that their distinct magnetic behaviours arise from their fac/mer configurations. Compared to fac-Dy(III), mer-Dy(III) possesses more axial ground-state KDs and higher first excited KDs.

Identification and validation of a TTN-associated immune prognostic model for skin cutaneous melanoma.

TTN is the most commonly mutated gene in skin cutaneous melanoma (SKCM). Tumor mutational burden (TMB) can generate new antigens that regulate the recognition of T cells, which will significantly affect the prognosis of patients. The TTN gene has a long coding sequence and a high number of mutant sites, which allows SKCM patients to produce higher TMB and may influence the immune response. It has been found that the overall survival (OS) of SKCM patients with TTN mutation was significantly higher than that of wild-type patients. However, the effect of TTN mutation on the immune microenvironment of SKCM has not been fully investigated. Here, we systematically explored the relationship and potential mechanisms between TTN mutation status and the immune response. We first revealed that TTN mutated SKCM were significantly associated with four immune-related biological processes. Next, 115 immune genes differentially expressed between TTN mutation and wild-type SKCM patients were found to significantly affect the OS of SKCM patients. Then, we screened four immune-related genes (CXCL9, PSMB9, CD274, and FCGR2A) using LASSO regression analysis and constructed a TTN mutation-associated immune prognostic model (TM-IPM) to distinguish the SKCM patients with a high or low risk of poor prognosis, independent of multiple clinical characteristics. SKCM in the low-risk group highly expressed a large number of immune-related genes, and functional enrichment analysis of these genes showed that this group was involved in multiple immune processes and pathways. Furthermore, the nomogram constructed by TM-IPM with other clinicopathological parameters can provide a predictive tool for clinicians. Moreover, we found that CD8+ T cells were significantly enriched in the low-risk group. The expression level of immune checkpoints was higher in the low-risk group than in the high-risk group. Additionally, the response to chemotherapeutic agents was higher in the low-risk group than in the high-risk group, which may be related to the long survival in the low-risk group. Collectively, we constructed and validated a TM-IPM using four immune-related genes and analyzed the potential mechanisms of TM-IPM to predict patient prognosis and response to immunotherapy from an immunological perspective.

[Treatment of extensive cervicomandibular scar in children and adolescent patients with bilateral expanded scapular flaps: report of 7 consecutive cases].

PURPOSE: To explore the feasibility of applying bilateral free expanded scapular flaps to treat extensive cervicomandibular scar in children and adolescents. METHODS: This study reviewed 7 children and adolescent patients who received bilateral expanded scapular flaps to treat extensive cervicomandibular scars in the Pediatric Plastic Surgery Ward from August 2018 to December 2020. The scars in all patients involved neck, mandible, and anterior chest. The cervical scars involved the anterior neck and one or both sides of the lateral neck, and there were varying degrees of cervical dysfunction and mandibular dysplasia. The operation was completed into two stages. In the first stage, the expanded circumflex scapular artery perforator flaps were designed on both sides of the back and soft tissue expanders were implanted. The expansion process lasted for 6-14 months. In the second stage, the scar tissue was removed and contracture was released, and the expanded flaps were harvested. The cervical wound was repaired with free flap transplantation by anastomosing the facial artery and vein with the circumflex scapular artery and vein. The donor sites were closed directly. RESULTS: In this series of 7 patients, one patient had poorly healed incision after the expander was implanted. One expanded flap ruptured before the second-stage surgery, which was successfully treated by secondary surgery. One patient had expansion problem due to the blockage of the internally placed injection bottle, which was treated by placing the injection bottle externally. One patient developed a small area of ischemic necrosis at the distal end of the flap after transplantation, which was treated conservatively with dressing change. The postoperative follow-up was 6 months to 2 years. The cervico-mandibular angle restored to normal range, the cervical extension, flexion, and rotation were significantly improved. Two patients underwent flap thinning and scar releasing. CONCLUSIONS: The route of the circumflex scapular artery is constant. Bilateral expanded scapular flap transplantation can be used to repair extensive cervicomandibular scar in children and adolescent patients. The flap donor site is concealed and secondary damage is minimal.

HOXA5 counteracts the function of pathological scar-derived fibroblasts by partially activating p53 signaling.

The inactivation of p53 can lead to the formation of pathological scars, including hypertrophic scars and keloids. HOXA5 has been reported to be a critical transcription factor in the p53 pathway in cancers. However, whether HOXA5 also plays a role in pathological scar progression through activating p53 signaling remains unknown. In this study, we first demonstrated that HOXA5 overexpression in hypertrophic scar-or keloids-derived fibroblasts decreased cell proliferation, migration and collagen synthesis, whereas increased cell apoptosis. Furthermore, the results of luciferase activity assays and ChIP PCR assays indicated that HOXA5 transactivated p53 by binding to the ATTA-rich core motif in the p53 promoter. HOXA5 also increased the levels of p21 and Mdm2, which are downstream targets of p53. Interestingly, silencing p53 in these pathological scar-derived fibroblasts partially attenuated HOXA5-mediated growth inhibition effect and HOXA5-induced apoptosis. In addition, 9-cis-retinoic acid augmented the expression of HOXA5 and promoted the effects of HOXA5 on pathological scar-derived fibroblasts, and these effects could be suppressed by HOXA5 knockdown. Thus, our study reveals a role of HOXA5 in mediating the cellular processes of pathological scar-derived fibroblasts by transcriptionally activating the p53 signaling pathway, and 9-cis-retinoic acid may be a potential therapy for pathological scars.

Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation.

In hypertrophic scar (HS) formation, the type 2 immune response induces the alternatively activated macrophages (M2), which manipulate fibroblasts to differentiate into myofibroblasts with active biologic functions and proliferation. Myofibroblasts express α-smooth muscle actin (α-SMA) and synthesize and produce additional collagen type I and collagen type III, inducing HS formation. However, studies on the mechanism of M2 macrophage modulation are only based on the recognition of profibrotic factors such as TGF-ß1 secreted by macrophages. The influence of exosomes from M2 macrophages on scar formation is still unknown. Both M2 macrophages and myofibroblasts highly express glutaminases (GLSs). GLS is a critical enzyme in glutaminolysis and is important for M2 macrophage and fibroblast polarization. In this study, we found that in a TGF-ß1-stimulated coculture system, a long noncoding RNA (lncRNA) named lncRNA-ASLNCS5088 was enriched in M2 macrophage-derived exosomes. This lncRNA could be transferred with high efficiency to fibroblasts and acted as an endogenous sponge to adsorb microRNA-200c-3p, resulting in increased GLS and α-SMA expression. Pretreatment with GW4869, which impairs M2 macrophage exosome synthesis, ameliorated these pathologic changes in fibroblasts in vitro. Local injection in the late scar formation period with GW4869 reduced α-SMA+ fibroblasts and alleviated the fibrosis of tissue after wound healing in vivo.-Chen, J., Zhou, R., Liang, Y., Fu, X., Wang, D., Wang, C. Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation.

METTL3 mediated m6A modification plays an oncogenic role in cutaneous squamous cell carcinoma by regulating ΔNp63.

The cutaneous squamous cell carcinoma (cSCC) originates from epithelial stem cells through the dysregulation of self-renewal and differentiation. Recent studies have identified methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification as key regulator of fate of stem cells. However, little is known about the functional importance of METTL3 in cSCC. Here, Western blot and immunohistochemistry were used to investigate the METTL3 levels in cSCC tissues. Functional experiments including surface marker detection, Brdu incorporation assay, colony forming assay, m6A dot blot and tumor xenograft assay were performed to investigate the properties in cSCC cell lines after METTL3 knock down. The expression of METTL3 was up-regulated in cSCC samples. METTL3 knock down impaired cSCC cell stem-like properties, including colony forming ability in vitro and tumorigenicity in vivo. Furthermore, METTL3 knock down and methylation inhibitor cycloleucine could decrease the m6A levels and the expression of ΔNp63 in cSCC. Exogenous expression of ΔNp63 partially restored the cell proliferation of METTL3-knockdown cSCC cells. Therefore, our data indicated the m6A methyltransferases METTL3 as a critical gene in regulating tumorigeneis of cSCC.

Phosphine Oxide Ligand Based Tetrahedral CoII Complexes with Field-induced Slow Magnetic Relaxation Behavior Modified by Terminal Ligands.

Two isostructural mononuclear CoII complexes, [Co(xantpo)(NCE)2 ] (E=S (1) and O (2); xantpo=9,9-dimethyl-4,5-bis(diphenylphosphoryl) xanthene), supported by a bidentate phosphine oxide ligand are reported. The cobalt complexes exhibit characteristic tetrahedral structures coordinated with two oxygen and two nitrogen atoms. Magnetic property measurements show their similar static magnetic behaviours but very different dynamic magnetic behaviours. Both complexes show field-induced slow magnetic relaxation behaviours, but the relaxation of 2 is much slower than that of 1. Fittings to the magnetic data and ab initio CASSCF calculations reveal significant changes in the zero field splitting (ZFS) parameters (D and E), which can be attributed to the small geometrical changes of the Co ions and the different ligand field strength of the two terminal ligands.

Mandibular Rim Trilogy with Botulinum Toxin Injection: Reduction, Projection, and Lift.

"Onabotulinum toxin A (Botox) revolution" has brought the fundamental change in the facial rejuvenation as well as the concept of microinjection. The aesthetic standard tends to be the "globalization"; however, Asians have different aesthetic cultures and unique facial features compared with Caucasians. A new rejuvenation concept is proposed during our practice; the Asian face should preserve the original facial identity during Botox treatments. The lower face is treated with botulinum toxin to achieve a harmonious facial profile. Twenty young females ranging in age from 30 to 45 years consented and received the three-pronged procedure from March 2014 to April 2015; photography at baseline and follow-up visit were taken and analyzed. After posttreatment for 2 months, significant improvement was observed compared with the baseline. And the reduced masseter prominence and prominent chin were obtained, showing a favorable facial contour and harmonious appearance during the follow-up. The novel three-pronged approach to lower facial rejuvenation was aimed at the Asian characteristic of hypertrophic masseter, chin retrusion, and the facial sagging during the aging process. Botox treatment was a quite effective and safe strategy to improve the appearance and contour of the lower face in Asian patients.

miR-21 promotes collagen production in keloid via Smad7.

OBJECTIVE: To explore the biological function of miR-21 in the formation of keloid. METHODS: Normal skin and keloid tissue samples underwent histopathologic study and qPCR analysis. The expression of miR-21 and mRNA expression of Smad7, Col1A1, Col3A1 in fibroblasts derived from keloid tissue and normal skin tissue samples were detected by qPCR. Normal and keloid fibroblasts were transfected with miR-21 mimics or inhibitor respectively, and expression of Smad7, Col1A1 and Col3A1 were examined. After the normal fibroblasts were transfected with Smad7 siRNA, expression of Col1A1 and Col3A1 were detected by Western blot and qPCR analysis. RESULTS: Collagen was obviously thick and disorganized in keloid tissue. The expression of miR-21, Col1A1 and Col3A1 in keloid tissue and keloid-derived fibroblasts were higher than that of normal counterparts, while the expression of Smad7 in keloid tissue and keloid-derived fibroblasts was lower. miR-21 mimics attenuated expression of Smad7, and enhanced the expression of Col1A1, Col3A1. Furthermore, the Smad7 siRNA increased expression of Col1A1and Col3A1. CONCLUSIONS: miR-21 promoted collagen production in keloid by negatively regulating the expression of the Smad7.