The biomarkers associated with epithelial-mesenchymal transition in human keloids.

INTRODUCTION: A keloid is a type of benign fibrotic disease with similar features to malignancies, including anti-apoptosis, over-proliferation, and invasion. Epithelial-mesenchymal transition (EMT) is a crucial mechanism that regulates the metastatic behavior of tumors. Thus, identifying EMT biomarkers is paramount in comprehensively understanding keloid pathogenesis. METHODS: To identify the differentially expressed genes (DEGs) GSE92566 dataset, with 3 normal skin and 4 keloid tissues, was downloaded from GEO databases to identify the differentially expressed genes (DEGs). Further, EMT-related genes were downloaded from dbEMT 2.0 databases and intersected with GSE92566 DEGs to identify EMT-related-DEGs (ERDEGs). Subsequently, the ERDEGs were used for GO, KEGG, gene set enrichment analysis (GSEA), protein-protein interaction (PPI), and miRNAs-mRNAs network analysis. To predict small molecules for EMT inhibition, the ERDEGs were imported to cMAP databases, whereas hub genes were imported to DGidb databases. Finally, we carried out qRT-PCR and in vitro experiments to validate our findings. RESULTS: A total of 122 ERDEGs were identified, including 59 upregulated and 63 down-regulated genes. Moreover, enrichment analysis revealed that focal adhesion, AMPK signal pathway, Wnt signal pathway, and EMT biological process were significantly enriched. STRING databases and Cytoscape software were used to construct the PPI network and EMT-related hub genes. Further, 3 modules were explored from the PPI network using the Molecular Complex Detection (MCODE) plugin. In the Cytohubba plugin, 10 hub genes were explored, including FN1, EGF, SOX9, CDH2, PROM1, EPCAM, KRT19, ITGB1, CD24, and KRT18. These genes were then enriched for the focal adhesion pathway. We constructed a microRNA (miRNA)-mRNA network, which predicted hsa-miR-155-5p (8 edges), hsa-miR-124-3p (7 edges), hsa-miR-145-5p (5 edges), hsa-miR-20a-5p (5 edges) and hsa-let-7b-5p (4 edges) as the most connected miRNAs regulating EMT. Based on the ERDEGs and 10 hub genes mentioned above, ribavirin demonstrated high drug-targeting relevance. Subsequently, qRT-PCR confirmed that the expression of FN1, ITGB1, CDH2, and EPCAM corroborated with previous findings. qRT-PCR also showed that the expression levels of hsa-miR-124-3p and hsa-miR-145-5p were significantly lower in keloids and hsa-miR-155-5p was upregulated in keloids. Finally, by treating human keloid fibroblasts (HKFs) with ribavirin in vitro, we confirmed that ribavirin could inhibit HKFs proliferation and EMT. CONCLUSION: In summary, this work provides novel EMT biomarkers in keloids and predicts new small target molecules for keloid therapy. Our findings improve the understanding of keloid pathogenesis, providing new treatment options.

Wip1 regulates wound healing by affecting activities of keratinocytes and endothelial cells through ATM-p53 and mTOR signaling.

BACKGROUND: As a p53-regulated gene, Wip1 regulates proliferation, migration, apoptosis, and senescence of several type cells, but its biological functions in keratinocytes and endothelial cells which are involved wound healing are not fully understood. This study aims to reveal the function and underlying mechanism of Wip1 in wound healing using models of transgenic animal, keratinocytes, and endothelial cells. METHODS: Using Wip1 knockout C57 BL/6 mice, we investigated effect of Wip1 deficiency on wound healing and angiogenesis; And using HaCaT and HUVEC as keratinocytes and endothelial cells, combined using primary keratinocytes from Wip1 knockout mice, we studied the effects of Wip1 knockdown/knockout or overexpression on proliferation, migration, and protein expressions of signaling components in ATM-p53 and mTOR pathway. RESULTS: Wip1 deficiency in mice impaired the wound repair and endothelial angiogenesis, reduced the thickness of granulation tissue, and decreased the number of Ki67-positive cells and CD31 positive vessels in granulation tissue. Knockdown of Wip1 by shRNAs suppressed the proliferation and migration of HaCaT and HUVEC cells and induced notably apoptosis in the two cells. In western blot, Wip1 knockdown enriched p53 and ATM proteins, while decreased activated AKT, mTOR and activated S6 ribosomal protein (pS6) levels in HaCaT and HUVEC cells. Ectopic expression of Wip1 decreased the p53 and ATM proteins, while increased activated AKT, mTOR and pS6 levels in HaCaT and HUVEC cells. And in primary keratinocytes from mice tail skin, Wip1 knockout increased p53 and ATM, while decreased activated AKT, mTOR and pS6 protein levels. CONCLUSION: Our study directly supports that Wip1 regulated skin wound healing possibly by affecting bioactivities including proliferation, migration and apoptosis of keratinocytes and endothelial cells at least through by modulating ATM-p53 and mTOR signaling.

Role of HIF-1α in pathogenic mechanisms of keloids.

BACKGROUDS AND OBJECTIVE: Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids. METHODS: We reviewed and summarized the relevant published studies. RESULTS: Hypoxia results in the accumulation of hypoxia-inducible factor 1α (HIF-1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial-mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance. CONCLUSION: It is, therefore, essential to understand the role of HIF-1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.

Anatomical Guidelines for Thigh Lipoplasty Based on Cadaveric Dissection of the Superficial Fascial System in the Thigh.

BACKGROUND: Although widely accepted as an optimal procedure in thigh contouring, liposuction can result in complications, such as skin irregularity or aspiration inadequacy. A main cause might be insufficient knowledge of the superficial fascial system (SFS). The authors aimed to explore the characteristics of the SFS in the thigh and propose anatomical guidelines and new zoning for liposuction-assisted thigh contouring. METHODS: A total of 20 fresh female thighs were dissected from the skin to deep fascia to observe and compare changes in the SFS from the medial to the lateral side and from the proximal to the distal end. RESULTS: The thigh was divided into four units, namely, the medial (three subunits: upper, middle, and lower), anterior, posterior (three subunits: upper medial, upper lateral, and middle lower parts), and lateral thigh. The authors found that the form of the SFS has regional variations. Therefore, based on these varied features, four anatomical scenarios (degrees I to IV) and one functional section (hip-contour support) were devised from the eight subunits. Five different liposuction methods were formulated to manage these subunits: all-layer mass liposuction, normal aspiration, border feather-out, restricted lipoplasty, and anchor. CONCLUSIONS: The SFS of the thigh showed a regional variation pattern, based on which the authors proposed a series of new anatomy-based liposuction approaches. A well-sculpted thigh with its different sections presented in harmony can be safely obtained using these approaches.

Studying Dynamics of Mid-face Lifting During Hyaluronic Acid Filler Injection Using Ultrasound Imaging.

BACKGROUND: The ageing in the mid-face involves volume deficiency in multiple anatomical units, including the zygomatic arch, infraorbital region, medial and lateral cheek and nasolabial fold (NLF). Hyaluronic acid (HA) is extensively used in the minimally invasive procedures of mid-face rejuvenation. OBJECTIVES: MD CodesTM is proposed to perform combined treatment of multiple sites to reduce treatment variability and increase clinician success rates. Although the detailed procedure of this technique, aesthetic effects and complications have been disclosed, its anatomical information has yet to be discussed. This paper elaborated on the static and dynamic anatomical characteristics of MD CodesTM through cadaveric dissection and ultrasound imaging. METHODS: Anatomical dissection and ultrasound imaging help us look back on the injection methods and anatomical principles of MD CodesTM. RESULTS: The treatment is threefold: (1) the bolus injections, for lifting purposes, are performed at the most depressing point along the zygomatic arch, zygomatic eminence, the prominent optimal point in the zygomatic region, the most depressed point of upper NLF with 0.2-0.3 ml HA. (2) The linear injections, featuring facial contouring refinement, are performed at the deep fat pad of the medial cheek and infraorbital region with 0.4 ml HA. (3) The linear injections, featuring volume replacement, are performed at the subcutaneous fat layer of lateral cheek and NLF with 0.8 and 0.4 ml HA. CONCLUSIONS: MD CodeTM is led by the principle of "less dosage and better effect", and a special injection sequence is formulated based on the anatomical characteristics. Ultrasound is a useful tool to make for a dynamic anatomical understanding of MD CodeTM and visualize the anatomical information such as layers and thicknesses. 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 .

Acupotomy in the treatment of tenosynovitis of hand flexor tendons: A systematic review and meta-analysis.

BACKGROUND: Acupotomy was used to treat tenosynovitis of hand flexor tendons (THFT) in China. But it's uncertain about the efficacy of acupotomy for THFT. We plan to evaluate the efficacy and safety about acupotomy therapy in the treatment of THFT through this review. METHODS: The protocol about this review was registered in PROSPERO (registration number: CRD42022330568). We searched 6 databases from their respective inception dates to January 11, 2022. Studies searched was screened by our reviewers, and then the raw data was filtered out. We used RevMan 5.3 software to perform statistical analysis. RESULTS: 11 studies involving 828 patients were shortlisted. The experimental group showed obvious advantages compared with the control group, such as effective rate (odds ratio [OR] = 6.77, 95% CI [confidence intervals] = [3.89, 11.77], P < .00001), cure rate (OR = 3.32, 95% CI = [1.81, 6.11], P = .0001) and Vas score (MD = -1.21, 95% CI = [-2.00, -0.42], Z = 3.01, P < .003). CONCLUSIONS: According to the above results, Acupotomy is an effective and safe treatment for THFT. So it should be recommended for the treatment of THFT patients.

GreenLight Laser photoselective vapo-enucleation of the prostate with front-firing emission versus plasmakinetic resection of the prostate for benign prostate hyperplasia.

BACKGROUND: Although the conventional, monopolar transurethral resection of the prostate (TURP) has proven to be an effective and relatively safe treatment for patients with benign prostatic hyperplasia (BPH), many new endoscopic technologies have been introduced to treat BPH. With the development of laser, there are several alternative transurethral procedures embracing laser therapies. Herein, this study sought to explore the efficacy, safety and follow-up of GreenLight laser photoselective vapo-enucleation of the prostate (PVEP) with front-firing emission compared with plasmakinetic resection of the prostate (PKRP) used to surgically manage BPH. METHODS: Data from patients who underwent either GreenLight laser PVEP or PKRP were retrospectively collected from March 2013 to May 2018. Perioperative data from both groups were compared. RESULTS: Totally, 43 and 45 patients were included in the PVEP and PKRP groups, respectively. No significant difference was observed in excision efficiency ratio (resected prostate weight/operation time) between the two groups (P=0.372). The efficiency ratio of the first 20 PVEP procedures (0.36±0.09 g/min) was significantly lower than that of the second 23 PVEP procedures (0.45±0.18 g/min) (P=0.042). The PVEP group experienced a shorter duration of catheterization, postoperative hospital stay and irrigation time than the PKRP group (P<0.001, P=0.001 and P<0.001, respectively). There was no statistically significant difference between the two groups (P=0.937) in terms of overall postoperative complications. Three months after surgery, the international prostate symptoms (IPSS) score, quality of life (QOL) score, postvoid residual (PVR) volume and maximum urinary flow rate (Qmax) were decreased in both groups (P<0.001 for all) and were comparable between both groups (P=0.635, 0.662, 0.671 and 0.924, respectively). CONCLUSIONS: GreenLight laser PVEP with front-firing emission was safe and effective modality in treating patients with BPH with short-term follow-up. PVEP was associated with shorter catheterization and postoperative hospital stay time compared with PKRP.

Myricitrin ameliorates ethanol-induced steatosis in mouse AML12 liver cells by activating AMPK, and reducing oxidative stress and expression of inflammatory cytokines.

It is necessary to identify compounds that may provide protection against alcoholic liver disease. To the best of our knowledge, the effect of myricitrin on the development of ethanol­induced liver disease has not been previously investigated. The present study aimed to determine the effect of myricitrin on ethanol­induced steatosis in AML12 mouse liver cells and to identify the underlying molecular mechanisms. Ethanol­treated AML12 cells exhibited significant improvement in viability following treatment with myricitrin. Oil red O staining indicated that myricitrin ameliorated ethanol­induced lipid accumulation in cells. Furthermore, following treatment with myricitrin, improvement in ethanol­induced steatosis and decrease in the levels of reactive oxygen species and lipoperoxides were observed in ethanol­stimulated cells. Myricitrin suppressed mRNA and protein expression of tumor necrosis factor­α, interleukin­6 and transforming growth factor­ß1 in ethanol­stimulated AML12 cells. Myricitrin markedly increased phosphorylation of adenosine monophosphate­activated protein kinase (AMPK) and significantly reduced mRNA expression of sterol­regulatory element­binding protein­1c (SREBP­1c) and fatty acid synthase in ethanol­stimulated AML12 cells. The results of the present study indicate that myricitrin ameliorates ethanol­induced steatosis in AML12 cells by attenuating oxidative stress, suppressing expression of certain inflammatory cytokines and modulating the AMPK/SREBP-1c pathway.