Identification and validation of CRLF1 and NRG1 as immune-related signatures in hypertrophic scar.

BACKGROUND: Hypertrophic scar (HTS) is a prevalent chronic inflammatory skin disorder characterized by abnormal proliferation and extracellular matrix deposition and the precise mechanisms underlying HTS remain elusive. This study aimed to identify and validate potential immune-related genes associated with hypertrophic scar formation. METHODS: Skin samples from normal (n = 12) and hypertrophic scar tissues (n = 12) were subjected to RNA-seq analysis. Differentially expressed genes (DEGs) and significant modular genes in Weighted gene Co-expression Network Analysis (WGCNA) were identified. Subsequently, functional enrichment analysis was performed on the intersecting genes. Additionally, eight immune-related genes were matched from the ImmPort database. Validation of NRG1 and CRLF1 was carried out using an external cohort (GSE136906). Furthermore, the association between these two genes and immune cells was assessed by Spearman correlation analysis. Finally, RNA was extracted from normal and hypertrophic scar samples, and RT-qPCR, Immunohistochemistry staining and Western Blot were employed to validate the expression of characteristic genes. RESULTS: A total of 940 DEGs were identified between HTS and normal samples, and 288 key module genes were uncovered via WGCNA. Enrichment analysis in key module revealed involvement in many immune-related pathways, such as Th17 cell differentiation, antigen processing and presentation and B cell receptor signaling pathway. The eight immune-related genes (IFI30, NR2F2, NRG1, ESM1, NFATC2, CRLF1, COLEC12 and IL6) were identified by matching from the ImmPort database. Notably, we observed that activated mast cell positively correlated with CRLF1 expression, while CD8 T cells exhibited a positive correlation with NRG1. The expression of NRG1 and CRLF1 was further validated in clinical samples. CONCLUSION: In this study, two key immune-related genes (CRLF1 and NRG1) were identified as characteristic genes associated with HTS. These findings provide valuable insights into the immune-related mechanisms underlying hypertrophic scar formation.

Efficacy of Fractional Micro-plasma Radio Frequency Technology in Treating Hypertrophic Burn Scars in Asian Patients Under General Anesthesia: A Retrospective Study of 104 Cases.

BACKGROUND: Laser and other energy devices have been widely used in the minimally invasive treatment of scars. Among various technologies, Fractional Micro-Plasma Radio Frequency Technology (FMRT) has gained extensive consensus in the treatment of various types of scars and skin disorders, such as wrinkles, skin laxity, and pigmentation. OBJECTIVE: This study is a retrospective clinical trial aimed at assessing the effectiveness and safety of FMRT for hypertrophic burn scars treatment in the Asian population under different anesthesia methods. METHODS: A total of 104 patients with hypertrophic burn scars treated in our department from May 2018 to May 2022 were selected. Scar assessment scales were applied to observe changes in scars before and after FMRT treatment. RESULTS: A prospective study of 104 patients found that female patients were more likely to undergo laser treatment under general anesthesia (P < 0.05). Postoperative VSS total score, VSS total score difference, and immediate postoperative pain score were all better with general anesthesia compared to local anesthesia (P < 0.05). There were more significant improvements in scar color, vascular distribution, and flexibility (P < 0.05). When comparing the treatment outcomes between females and males, it was found that general anesthesia patients were superior to local anesthesia patients in terms of color score, vascular distribution score, flexibility score, and postoperative VSS total score 6 months after the final treatment. General anesthesia patients had a shorter hospital stay. Overall treatment evaluation was better for female general anesthesia patients than male patients. CONCLUSION: General anesthesia combined with FMRT is an effective, safe, and more acceptable treatment method for hypertrophic burn scars in the Asian population. BULLET POINTS: In the Asian population, the combined use of general anesthesia and Fractional Micro-Plasma Radio Frequency Technology (FMRT) is an effective, safe, and accepted method for treating skin scars. LEVEL OF EVIDENCE II: 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 .

The Comparison of Efficacy and Safety Between General and Topical Anesthesia on Micro-Plasma Radiofrequency Treatment for Hypertrophic Scar: A Retrospective Cohort Study.

BACKGROUND: While micro-plasma radiofrequency (MPR) treatment has a significant impact on hypertrophic scars, patients often require anesthesia to alleviate substantial discomfort. Currently, patients with similar degrees of scarring may choose surface anesthesia or general anesthesia based on their personal preferences. Nevertheless, the effectiveness and safety of different anesthesia modalities remain uncertain. OBJECTIVE: To assess the effectiveness and safety of both general and surface anesthesia in MPR treatment for hypertrophic scars. METHODS: We conducted a retrospective cohort study involving 101 patients diagnosed with hypertrophic scars who underwent MPR with different anesthesia methods. The primary measures of efficacy included the Vancouver Scar Scale (VSS) scores assessed before the first treatment and six months after the final treatment. Pain relief was evaluated using Visual Analog Scale (VAS) scores. Safety was assessed by comparing the incidence of adverse reactions between the two groups. RESULTS: Patients in the general anesthesia group showed a significant difference in scar pigmentation 6 months after the treatment and lower pain level than those in the surface anesthesia group in the treatment of MPR. The difference in safety was not statistically significant. After adjusting for confounding factors and propensity score matching, the outcome of VSS and VAS scores was stable. CONCLUSION: General anesthesia, as opposed to surface anesthesia, appears to enhance both the effectiveness and safety of MPR while reducing postoperative pain in the treatment of hypertrophic scars. For patients with heightened pain sensitivity, general anesthesia may be the preferred treatment option. LEVEL OF EVIDENCE II: 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 http://www.springer.com/00266 .

Impact of SARS-CoV-2 Vaccination or Infection on the Safety and Efficacy of Aesthetic Injections: A Systematic Review.

BACKGROUND: Aesthetic injections have become increasingly popular for maintaining a youthful appearance. However, with the rise of SARS-CoV-2, there have been concerns about potential complications. This study aims to summarize and understand the complications that occur in individuals who have received cosmetic injections after SARS-CoV-2 infection or vaccination. By doing so, we hope to provide recommendations to minimize these complications and ensure the safety of aesthetic treatments in the current COVID-19 era. METHODS: The PRISMA guidelines, the Preferred Reporting Program for Systematic Reviews and Meta-Analyses, were used for this review. Databases including PubMed, EMBASE, Medline, Web of Science and ScienceDirect were searched. The last search time of each database was May 10, 2023. In addition, relevant references were manually searched. RESULTS: A total of 26 studies containing 139 patients were searched. The complication with the highest percentage of reported patients was delayed inflammatory response (DIR) (n = 68; 48.92%), followed by diminished efficacy (n = 45; 32.37%) and filler reaction (n = 12; 8.63%). The remaining complications include hypersensitivity reactions, symptomatic hypercalcemia, sub-acute hypersensitive reactions, hyperalgesia, infection, fat necrosis and granulomatous reaction. CONCLUSIONS: Cosmetic injectable procedures are generally safe but may have adverse effects, particularly during the pandemic. It is important for individuals to fully understand these risks beforehand. Clinicians should be knowledgeable about adverse event mechanisms and management to prevent issues. Industry leaders should strengthen risk management efforts to ensure safe and steady development of cosmetic injections. Overall, a comprehensive understanding, effective communication and risk management are crucial for the safe use of cosmetic injectable procedures. 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 at www.springer.com/00266 .

Superselective Arterial Hyaluronidase Thrombolysis is an Effective Treatment for Hyaluronic Acid-Induced Retinal Artery Occlusion: Study in a Rabbit Model.

BACKGROUND: There are serious complications associated with hyaluronic acid (HA) facial injections, including vision impairment due to retinal artery ischemia. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in rabbit. We used this to verify the efficacy of hyaluronidase intra-artery thrombolysis in the treatment of hyaluronic acid-induced retinal artery occlusion. METHODS: Retinal artery ischemia was induced by injecting HA into the ophthalmic artery (OA) of adult chinchilla rabbit, and reperfusion was achieved by intra-artery thrombolysis therapy with hyaluronidase following 60 min and 4 h of occlusion. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow in the retina. Electroretinogram (ERG), hematoxylin and eosin staining and transmission electron microscope were used to evaluate the structure and function of the retina after ischemia and reperfusion following 60 min and 4 h of occlusion. RESULTS: DSA and FFA images confirmed occlusion of the ophthalmic and central retinal arteries, as well as reperfusion after hyaluronidase thrombolysis. ERG indicated retinal dysfunction following ischemia, and thrombolysis partially rescued its impairment following 4 h of occlusion. Hematoxylin and eosin staining and TUNEL staining revealed ischemia-induced histological damages in the retina at different time windows, and hyaluronidase thrombolysis partially mitigated these damages. CONCLUSIONS: We report a method to establish a HA-induced retinal artery occlusion animal model. Hyaluronidase intra-artery thrombolysis was used to recanalize the embolized OA at different time points. Using our method, we achieved retinal reperfusion, and an improvement was observed in the visual function of rabbits after hyaluronidase thrombolysis following 4 h of occlusion. We believe that hyaluronidase intra-artery thrombolysis is an effective method to treat HA-induced retinal artery occlusion in clinic. LEVEL OF EVIDENCE II: 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 .

Efficacy of Superselective Intra-arterial Recanalization of Embolized Arteries Resulting from Facial Hyaluronic Acid Injection.

BACKGROUND: Arterial embolism is a rare complication caused by hyaluronic acid (HA) injection. However, it is one of the most serious complications. Once it happens, the complication would have a great and long-term impact on patients. Intra-arterial recanalization has been reported for recovering the visual acuity in patients with visual loss caused by hyaluronic acid. There is little report about the benefits of superselective intra-arterial recanalization therapy for skin wounds caused by hyaluronic acid vascular embolization. METHODS: Eight patients who had received the superselective intra-arterial recanalization therapy were retrospectively reviewed. Hyaluronidase was injected into the facial artery by superselective intra-arterial recanalization therapy, followed by symptomatic treatment. The facial artery recanalization was successfully performed and no interventional procedure-related adverse events happened. RESULTS: Arterial embolization accompanies by the interruption or reduction of blood supply, followed by ochrodermia, pain, numbness, swelling, yellowish white secreta and even necrosis on skin wound area. Early detection of skin blood supply disorders and early recovery of blood supply are very critical to treat facial artery embolization caused by HA. After superselective intra-arterial recanalization therapy, the blood supply to facial skin was restored and skin wounds recovered in all patients. Only 1 patient was left with small and superficial scars. CONCLUSION: Superselective intra-arterial recanalization therapy is an effective and safe method that can alleviate skin wounds caused by HA vascular embolization. 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 .

Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Exploring Superselective Intraarterial Thrombolysis for Autologous Fat Injection-Induced Vision Loss.

BACKGROUND: Intravascular injection represents the most severe complication in fat transplantation procedures. Currently, the prognosis for patients who suffer from blindness due to fat transplantation-induced ocular vascular occlusion is far from optimistic. OBJECTIVES: The aim of this study was to explore and evaluate the efficacy and safety of arterial thrombolysis in the treatment of ocular vascular occlusion caused by fat transplantation. METHODS: We analyzed the data of 12 patients who underwent intraarterial thrombolysis and conservative treatments for facial autologous fat grafting-associated ocular vascular occlusion. Among the cases, there were 6 instances of ophthalmic artery embolism and 6 cases of central retinal artery occlusion. All patients suffered with sudden blindness, sometimes accompanied by eye pain, ptosis, strabismus, skin necrosis at the injection site, or cerebral microinfarction. They received symptomatic conservative treatments and intraarterial thrombolysis, encompassing mechanical vessel recanalization, vessel dilation, and dissolution of thrombus constituents. RESULTS: Following intraarterial thrombolysis, a noteworthy improvement in the blood flow of both the main trunk and peripheral branches of the ophthalmic artery was observed in the majority of patients when contrasted with their pretreatment status. One patient experienced a headache intraoperatively, while no significant discomfort was reported by the remaining patients. After conservative treatments and intraarterial thrombolysis, all patients experienced improvement in ocular symptoms, skin necrosis, and cerebral infarction. Three patients demonstrated improvement in visual acuity. These patients had surpassed the recommended time window for treatment, yet the occlusion of the ophthalmic artery was not complete. CONCLUSIONS: Intraarterial thrombolysis combined with conservative treatments achieves early perfusion and is expected to promote visual recovery. Hospitals that possess the necessary treatment capabilities are encouraged to establish this therapeutic pathway.

Concentrated Growth Factor (CGF): The Newest Platelet Concentrate and Its Application in Nasal Hyaluronic Acid Injection Complications.

BACKGROUND: Several cases of wounds caused by vascular compromise after facial cosmetic injection have been reported in recent years. How to promote wound healing, restore facial appearance, and avoid secondary injury in such patients have remained a clinical challenge. Our study was designed to assess the effect of concentrated growth factor (CGF) for repairing nasal wounds after nasal hyaluronic acid injection. METHODS: Six women with nasal wounds after hyaluronic acid injection were enrolled from June 2019 to June 2022. The average time of the first CGF treatment from admission was 2-4 days. CGF gel was prepared from each patient's blood by using a Medifuge™ system. After debridement of the wound, the prepared CGF gel was applied on the wound surface, and the wound dressing was fixed to stabilize the CGF gel. The CGF treatment interval was 3-4 days. RESULTS: The wound began to heal after the first CGF treatment. After 2-3 CGF treatments, the wound was almost completely healed. There was no deflection of the nasal columella, and nasal ventilation function was good. There was no obvious deformity in the appearance of the nose. After follow-up ranging from 2 months to 1 year, the appearance and function of the nose showed satisfactory recovery. CONCLUSIONS: CGF has great potential in promoting wound healing and restoring the appearance after complications from nasal hyaluronic acid injection. The preparation of CGF gel is simple, and the clinical application is convenient and safe. In future, more clinical trials are needed to further prove the efficacy and safety of CGF in the treatment of wounds secondary to cosmetic injection. 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 http://www.springer.com/00266 .

Efficacy and Safety of Pressure Therapy Alone and in Combination with Silicone in Prevention of Hypertrophic Scars: A Systematic Review with Meta-analysis of Randomized Controlled Trials.

BACKGROUND: At present, there are many kinds of hypertrophic scar treatment methods, among which pressure therapy and silicone therapy are very common and standard therapies, but whether they are used alone or in combination is still controversial. Therefore, the purpose of this systematic review was to compare the efficacy and safety of the combination of pressure therapy and silicone therapy (PTS) with pressure therapy alone (PT) in the treatment of hypertrophic scars to provide clinicians with information so that they can make better decisions. METHODS: Relevant randomized controlled trials (RCTs) were collected by searching PubMed, Ovid MEDLINE, Embase, ScienceDirect, Web of Science, The Cochrane Library, Scopus, and Google Scholar databases to assess scar scores (The Vancouver Scar Scale, VSS; Visual Analog Scale, VAS) and adverse effects. RESULTS: We screened 1270 articles and included 6 RCTs including 228 patients. We found that height (MD = 0.15, 95%CI 0.10-0.21, p < 0.01) and pliability (MD = 0.35, 95%CI 0.25-0.46, p <0.01) had a significant difference, these two measures showed that the PTS group was superior to the PT group. Results in other aspects, such as VSS, vascularity, pigmentation, VAS, and adverse effects were similar between the two groups. CONCLUSIONS: There was no significant difference between PTS and PT in the overall treatment efficacy of hypertrophic scars with similar VSS and adverse effects, but PTS might have potential benefits for height and pliability. Additional studies with larger sample size and sound methodological quality are needed to confirm our conclusions. 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 .

Efficacy of Percutaneous Superficial Temporal Arterial Hyaluronidase Injection for Hyaluronic Acid Filler-Induced Necrosis of Frontotemporal Skin and/or the Ipsilateral Scalp With Subsequent Alopecia.

BACKGROUND: Necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after hyaluronic acid (HA) filler injection into the temple is rare complications with superficial temporal artery embolization are suspected as the major pathological mechanism. The main treatment currently is intralesional hyaluronidase (HAase) injection, but the effectiveness of percutaneous superficial temporal arterial HAase injection still lacks consensus. OBJECTIVES: To investigate the effectiveness of superficial temporal arterial HAase injection in dissolving HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia. METHODS: Five recent clinical cases with necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after HA filler injection into the temple were analyzed retrospectively. The patients underwent HAase injection via superficial temporal artery combined with adjunctive treatments, and the clinical progress was observed. RESULTS: Significant improvement was observed in terms of necrosis of frontotemporal skin and the ipsilateral scalp after treatment, and the patients were relieved of their clinical symptoms. Alopecia occurred approximately 1 to 2 weeks after HA filler injection, and the well-defined alopecia areas were formed 15 to 20 days after HAase injection. Patients were followed for 3 to 6 months. During follow-up, the skin lesions of all patients were restored to near normal appearance. Hair regrowth was observed 2 to 3 months after HAase treatment, and hair density nearly reached the normal level 3 to 4 months later. CONCLUSIONS: Percutaneous superficial temporal arterial HAase injection is an effective treatment option for HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia.

CCN1 secreted by human adipose-derived stem cells enhances wound healing and promotes angiogenesis through activating the AKT signalling pathway.

The study aimed to explore the role of cellular communication network factor 1 (CCN1) an extracellular matrix protein in hADSC-treated wound healing. Immunofluorescence and enzyme-linked immunosorbent assays (ELISA) were used to demonstrate the secretion of CCN1 by hADSCs, isolated from human fat tissue. We investigated the role of CCN1 in wound healing by knockdown of CCN1 expression in hADSCs using CCN1 siRNA. Conditioned medium of hADSCs or hADSCs with CCN1 knocked down (hADSC-CMCCN1↓ ) was collected. After treatment with plain DMEM/F12, hADSC-CM, hADSC-CMCCN1↓ , or recombinant human CCN1 (rhCCN1), the wound healing abilities of human umbilical vascular endothelial cells (HUVECs) were assayed, and the AKT, also known as protein kinase B (PKB), signalling pathway was detected using western blotting. Next, we created full-thickness skin wounds on the backs of the mice and different treatments were applied to the wound surface. Wound size was measured using a digital camera on days 0-10, and evaluated. H&E and immunohistochemical staining were performed, and laser Doppler perfusion imaging was used to evaluate blood perfusion. The wound model and wound-healing assay showed that the hADSCs-CM and rhCCN1 groups had enhanced wound healing compared to the hADSCs-CMCCN1↓ group. Further, CCN1 and hADSCs-CM promoted the proliferation and migration of HUVECs through the AKT signalling pathway. We concluded that CCN1 secreted by hADSCs enhances wound healing and promotes angiogenesis by activating the AKT signalling pathway. CCN1 plays a vital role in the regulation of hADSCs-CM during wound healing.

Global research status of pathological scar reported over the period 2001-2021: A 20-year bibliometric analysis.

Pathological scar is a classic problem in plastic and reconstructive surgery. Although the researches on pathological scar have been conducted for decades, the way to go to address this thorny problem still remains challenging. To the best of our knowledge, few bibliometric analysis concerning pathological scar have been reported. In this study, we set out to employ bibliometric and visual analysis to offer research status and trends of pathological scar over the period 2001-2021. All publications covering pathological scar during 2001-2021 were retrieved and extracted from the Web of Science database. We applied VOSviewer software to evaluate the keywords and research hotpots, and the online tool (http://bibliometric.com/) was used to carried out the publication trends analysis. A total of 2221 pathological scar-related articles were identified over the period 2001-2021. China is the country which had the largest volume of publications (819, 36.87%), followed by the United States (416, 18.73%), Japan (144, 6.48%), Korea (142, 6.39%), and England (118, 5.31%). Among the institutions and journals, Shanghai Jiao Tong University (167) and Wound Repair and Regeneration (85) accounted for the most papers related to pathological scar, respectively. Professor Bayat A, who had the most citation frequency (2303), made great contribution in pathological scar field. "Fibroblast", "expression", and "proliferation" were identified as the pathological scar research hotspot through analysis of the keywords. In terms of publication, China ranked first all over the world, but the numbers of publication are inconsistent with the citation frequency, ranking first and second, respectively. Shanghai Jiao Tong University and journal Wound Repair and Regeneration stand for the highest level of research in this field to a certain extent. In the early stage, the research focus was mainly on the prevention, treatment, and risk factors for recurrence of pathological scar from cases. In the later stage, the research focus was on the comprehensive management, in which the mechanism research was in-depth to the molecular and gene level.

Splint-free line drawing model: An innovative method for excisional wound models.

The physiological phenomenon of wound contraction in mice cannot completely imitate the process of human skin regeneration, which is primarily attributed to reepithelialisation. As such, excisional wound models in mice are considered to be imperfect comparisons. This study aimed to enhance the correlation of mouse excisional wound models with that of humans, and to offer more practical and accurate ways to record and measure wound areas. We present evidence that simple excisional wounds produce a robust and stable wound model by comparing splint-free and splint groups. We monitored reepithelialisation and contraction in the C57BL/6J mouse excision wound model at different time points and prove that excisional wounds heal by both contraction and reepithelialisation. Some parameters were measured and a formula was used to calculate the area of wound reepithelialisation and contraction. In our results, reepithelialisation accounted for 46% of the wound closure of full-thickness excisional wounds. In conclusion, excisional wound models can be used as wound-healing models and a straightforward formula may be used to determine the process of reepithelialisation over a wound bed created by a simple excisional rodent wound model.

Engineering of global transcription factor FruR to redirect the carbon flow in Escherichia coli for enhancing L-phenylalanine biosynthesis.

BACKGROUND: The catabolite repressor/activator protein (FruR) is a global regulatory protein known to control the expression of several genes concerned with carbon utilization and energy metabolism. This study aimed to illustrate effects of the FruR mutant on the L-phenylalanine (L-PHE) producing strain PHE01. RESULTS: Random mutagenesis libraries of fruR generated in vitro were first integrated into the chromosome of PHE01 by CRISPR/Cas9 technique, and then the best mutant PHE07 (FruRE173K) was obtained. With this mutant, a final L-PHE concentration of 70.50 ± 1.02 g/L was achieved, which was 23.34% higher than that of PHE01. To better understand the mechanism, both transcriptomes and metabolomes of PHE07 were carried out and compared to that of PHE01. Specifically, the transcript levels of genes involved in gluconeogenesis pathway, pentose phosphate pathway, Krebs cycle, and glyoxylate shunt were up-regulated in the FruRE173K mutant, whereas genes aceEF, acnB, and icd were down-regulated. From the metabolite level, the FruRE173K mutation led to an accumulation of pentose phosphate pathway and Krebs cycle products, whereas the products of pyruvate metabolism pathway: acetyl-CoA and cis-aconic acid, were down-regulated. As a result of the altered metabolic flows, the utilization of carbon sources was improved and the supply of precursors (phosphoenolpyruvate and erythrose 4-phosphate) for L-PHE biosynthesis was increased, which together led to the enhanced production of L-PHE. CONCLUSION: A novel strategy for L-PHE overproduction by modification of the global transcription factor FruR in E. coli was reported. Especially, these findings expand the scope of pathways affected by the fruR regulon and illustrate its importance as a global regulator in L-PHE production.

To Explore Ideas From the Altered Metabolites: The Metabolomics of Pathological Scar.

BACKGROUND: Pathological scars are dermal fibroproliferative disorders due to rapid inflammatory response after dermal injury. The altered metabolites could reflect pathophysiological changes directly. However, it has not cleared how the metabolites change scars. OBJECTIVE: To explore new ideas of pathological scars from the altered metabolites by using ultra-performance liquid chromatography coupled to tandem mass spectrometry and identifying the key genes. METHODS: Keloid (KS, n = 10), hypertrophic scar (HS, n = 10), and normal skin (NS, n = 10) were collected. Ultra-performance liquid chromatography coupled to tandem mass spectrometry was used to identify and characterize metabolites. Differential metabolites were analyzed by orthogonal partial least square discriminant analysis and Student t test. The key pathways were analyzed via Kyoto Encyclopedia of Genes and Genomes, and the related enzymes were verified by real-time Polymerase Chain Reaction, both in tissues and their dermal fibroblasts. RESULTS: Two hundred fourteen metabolites were detected in total, mostly were fatty acids and amino acids. In the KS and NS groups, 65 different metabolites were screened ( P < 0.05), and the polyunsaturated fatty acids (PUFAs) metabolism and butyric acid in keloid should be concerned. The messenger Ribonucleic Acid expression of fatty acid desaturase 1 and fatty acid desaturase 2, which are the key enzyme of PUFA metabolism, were lower in KS and keloid-derived fibroblasts, P < 0.05. In HS group, 17 metabolites were significantly different and branched chain amino acids degradation was the key pathway. Moreover, branched chain keto acid dehydrogenase E1 subunit alpha was lower expressed in HS and their fibroblasts compared with NS, P < 0.05. CONCLUSIONS: Polyunsaturated fatty acids and butyric acid may be associated with the generation of keloids. The pathogenesis of hypertrophic scars may be involved in branched chain amino acids degradation, which is worth paying attention to.

Efficacy of Percutaneous Intraarterial Facial/Supratrochlear Arterial Hyaluronidase Injection for Treatment of Vascular Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.

BACKGROUND: Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. OBJECTIVES: The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. METHODS: We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. CONCLUSIONS: It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.

The role of altered fatty acid in pathological scars and their dermal fibroblasts.

PURPOSE: The proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation. METHODS: Hypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids (n = 10), hypertrophic scars (n = 10), and normal skin samples (n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). RESULTS: Compared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (∗p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all ∗p < 0.05). However, the mRNA levels of SREBP1 (∗∗∗p = 0.0002) and FASN (∗∗∗p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both ∗p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs (p > 0.05). CONCLUSION: FAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.

Chyloid Fat Carried Adipose-Derived Mesenchymal Stem Cells Accelerate Wound Healing Via Promoting Angiogenesis.

ABSTRACT: Impaired wound healing is responsible for significant morbidity and mortality worldwide. It is necessary to find a stable, efficient, and safe method to promote soft tissue wound healing. Fat grafting has become increasingly popular in contouring procedures. However, more recently, there has been an emphasis on its regenerative potential. In this study, we established the wound healing model using nude mice. Hematoxylin and eosin and Masson stainings were performed to assess the effect of chyloid fat on the histology of wound healing. A laser Doppler perfusion imager was used to evaluate the blood perfusion of wounds. Immunohistochemistry was carried out to detect the expression of CD31 in wound tissues. The results suggested that after treatment with granule fat or chyloid fat, wound healing was accelerated and blood perfusion was promoted. In addition, granule fat or chyloid fat treatment promoted the angiogenesis of the wound. In addition, we evaluated the amount of adipose-derived mesenchymal stem cells in chyloid fat and granule fat. It was found that chyloid fat contained more adipose-derived mesenchymal stem cells than granule fat did. In conclusion, we proved that chyloid fat could significantly accelerate the wound healing process via promoting angiogenesis. The adipose-derived mesenchymal stem cell plays a critical role in this effect of chyloid fat.

Chyle Fat-Derived Stem Cells Conditioned Medium Inhibits Hypertrophic Scar Fibroblast Activity.

BACKGROUND: Hypertrophic scars (HSs) generally form after injury to the deep layers of the dermis and are characterized by excessive collagen deposition. An increasing amount of evidence has determined that human adipose tissue-derived mesenchymal stem cells attenuate fibrosis in various conditions. We explored the effect and possible mechanism of chyle fat-derived stem cells (CFSCs) on HS formation. METHODS: Hypertrophic scar-derived fibroblasts (HSFs) and CFSCs were isolated from individual patients. Third-passage CFSCs were isolated and cultured using a mechanical emulsification method, and their surface CD markers were analyzed by flow cytometry. The adipogenic and osteogenic differentiation capacity of the CFSCs was determined using oil red O staining and alizarin red S staining, respectively. Then, the effects of CFSCs on HSFs were assessed in vitro. Hypertrophic scar-derived fibroblasts were treated with starvation-induced conditioned medium from the CFSCs (CFSC-CM). The change in HSF cellular behaviors, such as cell proliferation, migration, and protein expression of scar-related molecules, was evaluated by cell counting assay, scratch wound assay, enzyme-linked immunosorbent assay, and western blotting. All data were analyzed using SPSS 17.0. RESULTS: The CFSCs expressed CD90, CD105, and CD73 but did not express CD34, CD45, or CD31. The CFSCs differentiated into adipocytes and osteoblasts under the appropriate induction conditions. Chyle fat-derived stem cells conditioned medium inhibited HSF proliferation and migration. The in vitro and ex vivo studies revealed that CFSC-CM decreased type I collagen, type III collagen, and α smooth muscle actin expression. CONCLUSIONS: Our results suggest that CFSCs are associated with the inhibition of fibrosis in HSFs by a paracrine effect. The use of CFSC-CM may be a novel therapeutic strategy for HSs.