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.

Salicylic acid attenuates brassinosteroid signaling via protein de-S-acylation.

Brassinosteroids (BRs) are important plant hormones involved in many aspects of development. Here, we show that BRASSINOSTEROID SIGNALING KINASEs (BSKs), key components of the BR pathway, are precisely controlled via de-S-acylation mediated by the defense hormone salicylic acid (SA). Most Arabidopsis BSK members are substrates of S-acylation, a reversible protein lipidation that is essential for their membrane localization and physiological function. We establish that SA interferes with the plasma membrane localization and function of BSKs by decreasing their S-acylation levels, identifying ABAPT11 (ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17-LIKE ACYL PROTEIN THIOESTERASE 11) as an enzyme whose expression is quickly induced by SA. ABAPT11 de-S-acylates most BSK family members, thus integrating BR and SA signaling for the control of plant development. In summary, we show that BSK-mediated BR signaling is regulated by SA-induced protein de-S-acylation, which improves our understanding of the function of protein modifications in plant hormone cross talk.

Post-rhinoplasty complications with previous hyaluronic acid injection history: Cerebral infarction and vision loss.

BACKGROUND: Rhinoplasty is becoming increasingly frequent as the pursuit of aesthetics by people accelerates. In recent years, the proportion of people opting for rhinoplasty injections has gradually increased. This has led to numerous reports citing catastrophic postoperative complications such as skin necrosis, cerebral infarction, and visual impairment. AIM: The aim of our report is to discuss the possible etiological factors for this post-rhinoplasty complication and provides a rationale for HA injection history as a risk factor in rhinoplasty. METHODS: We report a rare case that received nasal HA injections in the past without any untoward incident. She opted for a second rhinoplasty 2 years after her initial nasal HA injections. This second intervention led to post-injection loss of vision in one eye and cerebral infarction. Following clinical and radiological examination, digital subtraction angiography (DSA) and superselective intra-arterial thrombolysis were performed. RESULTS: The patient did not develop disuse exotropia or ocular atrophy, but the left eye remained without light perception, which implies that intra-arterial thrombolytic therapy may be a positive and effective method to maintain the normal appearance of the eye. CONCLUSION: It is advisable for patient safety to maintain a long interval of time between hyaluronidase injection and repeat rhinoplasty. Clinicians should become familiar with the anatomical peculiarities of the patient and be gentle during the rhinoplasty procedure.

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.

Gelatin methacryloyl (GelMA) loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells(ADSCs) conditioned medium promotes wound healing and vascular regeneration in aged skin.

BACKGROUND: Aging skin is characterized by a disturbed structure and lack of blood supply, which makes it difficult to heal once injured. ADSCs secrete large amounts of cytokines, which promote wound healing and vascular regeneration through paracrine secretion, and the number of cytokines can be elevated by hypoxic pretreating. However, the components of ADSCs are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel synthesized from gelatin and has recently emerged as a potentially attractive material for tissue engineering applications. GelMA loaded with concentrated hypoxic pretreated ADSCs conditioned medium could provide a new method of treating wounds in aged skin. METHODS: Primary ADSCs were isolated from human adipose tissue and characterized by flow cytometry and differentiation test. ADSCs in passages 4-6 were pretreated in the hypoxic and normoxic environments to collect conditioned medium, the conditioned medium was then concentrated to prepare concentrated ADSCs conditioned medium(cADSC-CM)(the one collected from ADSCs under hypoxia was called hypo-CM ,and the one from normoxia was called nor-CM). The concentration of cytokines was detected. After treated with cADSC-CM, the abilities of proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs) were assayed, and Akt/mTOR and MAPK signal pathway was detected using western blotting. GelMA+hypo-CM hydrogel was prepared, and a comprehensive evaluation of morphology, protein release efficiency, degradation rate, mechanical properties, and rheology properties were performed. Full-thickness skin wounds were created on the backs of 20-month-old mice. After surgery, GelMA, GelMA+F12, GelMA+hypo-CM, and GelMA+nor-CM were applied to the wound surface respectively. H&E, Masson, and immunohistochemistry staining were performed, and a laser Doppler perfusion imager was used to evaluate the blood perfusion. The student's t-test was used for analysis between two groups and a one-way analysis of variance (ANOVA) was used for analysis among multi groups. RESULTS: Our results revealed that 1) wounds in aged skin healed more slowly than that in young skin and exhibited poorer perfusion; 2) hypoxic pretreated ADSCs secreted more cytokines including VEGF by activating HIF1α; 3) hypo-CM promoted proliferation and migration of HUVECs through VEGF/Akt/mTOR and MAPK signal pathway; 4) GelMA-hypoCM accelerated wound healing and angiogenesis in aged skin in vivo. CONCLUSION: GelMA loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells conditioned medium could accelerate wound healing in aged skin by promoting angiogenesis.

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.

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.

Two homologous protein S-acyltransferases, PAT13 and PAT14, cooperatively regulate leaf senescence in Arabidopsis.

Lipid modification on the cysteine residues of proteins, known as S-palmitoylation or S-acylation, regulates the subcellular localization and the function of proteins. S-acylation is catalysed by a group of protein acyltransferases (PATs) with a conserved Asp-His-His-Cys (DHHC) motif. The molecular function of S-acylation has been studied in details in yeast and mammalian cells, but its role in plant cells remains unclear. Here it is reported that the expression of two homologous protein acyltransferases- PAT13 and PAT14 -was moderately increased in the older leaves of Arabidopsis. The double mutant of PAT13 and PAT14 displayed a severely early leaf senescence phenotype. The phenotype was complemented by PAT13 or PAT14 overexpression in the double mutant, confirming the roles of PAT13 and PAT14 in this process. Furthermore, the levels of reactive oxygen species (ROS) and cell death were dramatically induced in the double mutant. To investigate the molecular functions of PAT13 and PAT14, their potential S-acylation substrates were predicted by bioinformatics methods. The subcellular localization and S-acylation of a candidate substrate NITRIC OXIDE ASSOCIATED 1 (NOA1), which also plays a role in leaf senescence control, were partially disrupted in the protoplasts of the double mutant. Impairment of S-acylation on NOA1 affected its subcellular localization and its function in leaf senescence regulation. Conclusively, protein S-acyltransferases PAT13 and PAT14 are involved in leaf senescence control- possibly via NOA1 S-acylation-, providing a new sight into the regulation mechanism of S-acylation in leaf senescence.