Keloid Patients Research Articles

The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target

Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we found that the characteristics of stem-like cells from keloid lesions and the surrounding dermis differ from those of normal skin. Furthermore, the HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient–derived stem-like cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, the HH signal inhibitor vismodegib reduced keloid reconstituted tumor size and keloid-related gene expression in nude mice and the collagen bundle and expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic targets of keloids.

Effect of Epidermoid Cysts on the Efficacy of Intralesional Corticosteroid Therapy for Hypertrophic Scars and Keloids: A Prospective Pilot Study.

Patients with hypertrophic scars (HSs) or keloids occasionally have epidermoid cysts (ECs), and the effect of ECs on the effectiveness of intralesional corticosteroids (ILCs) treatment in these patients has not been reported. This study aims to evaluate the influence of ECs on the outcomes of ILCs treatment in patients with HSs or keloids. This prospective study included 572 patients with keloids ( n = 461) or HSs ( n = 111). Patients received intralesional triamcinolone acetonide injection (0.05 mL/injection) at a concentration of 40 mg/mL and every 28 days for 4 sessions, with a 1-year follow-up. A higher incidence of ECs was observed in keloid patients (16.92%) compared with HSs patients (7.21%). Keloid patients with ECs were older ( p = .008) and had a longer disease duration ( p = .0148), higher Vancouver scar scale (VSS) scores ( p = .04), and greater thickness ( p = .006). Keloid patients with ECs showed less improvement in VSS scores ( p < .0001) and thickness ( p < .0001) after ILCs treatment, with a higher recurrence rate ( p < .0001). The overall complication rate in keloid patients with ECs after ILCs treatment was 49.51%. Epidermoid cysts under keloids were associated with a poor response to ILCs therapy. Therefore, it is recommended to incorporate ultrasonography as a routine examination for keloid patients to aid in better decision making in clinical practice.

Needle-free electronically controlled jet injection with corticosteroids in recalcitrant keloid scars: a retrospective study and patient survey

First-line treatment of keloids consists of intralesional needle injections with corticosteroids, but generally entails multiple painful sessions, resulting in variable clinical outcomes. Novel needle-free jet injectors may facilitate more effective and patient-friendly dermal drug delivery. Here, we evaluated the effectiveness, tolerability and patient satisfaction of intralesional triamcinolone-acetonide (TCA) treatment in recalcitrant keloids using an electronically controlled pneumatic injector (EPI). A retrospective study was conducted in recalcitrant keloid patients with a history of severe pain during needle injections who received three sessions of EPI + TCA. Outcome measures included Patient and Observer Scar Assessment Scale (POSAS), Global Aesthetic Improvement Scale (GAIS), treatment-related pain (NRS), adverse effects, and patient satisfaction (survey). Ten patients with in total 283 keloids were included. The POSAS score significantly improved at follow-up and GAIS was reported as ‘(very) improved’ for all patients. EPI + TCA was well-tolerated with a significantly lower NRS pain score compared to needle + TCA (pilot treatment). Only minor adverse effects occurred, and 90% of patients preferred EPI over needle treatment. EPI + TCA is an effective and tolerable treatment for patients with recalcitrant keloids. The minimal treatment-related pain and high patient satisfaction makes it a promising treatment for patients with needle-phobia and/or severe pain during needle injections.

Benzbromarone Induces Targeted Degradation of HSP47 Protein and Improves Hypertrophic Scar Formation

Fibrotic diseases are characterized by the abnormal accumulation of collagen in the extracellular matrix (ECM), leading to the functional impairment of various organs. In the skin, excessive collagen deposition manifests as hypertrophic scars and keloids, placing a substantial burden on patients and the health care system worldwide. Heat shock protein 47 (HSP47) is essential for proper collagen assembly and contributes to fibrosis. However, identifying clinically applicable HSP47 inhibitors has been a major pharmaceutical challenge. Here, we identified benzbromarone (BBR) as a HSP47 inhibitor for hypertrophic scarring treatment. BBR inhibited collagen production and secretion in fibroblasts from keloid patients by binding to HSP47 and inhibiting the interaction between HSP47 and collagen. Interestingly, BBR not only inhibits HSP47 but also acts as a molecular glue degrader that promotes its proteasome-dependent degradation. Through these molecular mechanisms, BBR effectively reduced hypertrophic scarring in mini pigs and mice with burns and/or excisional skin damage. Thus, these findings suggest that BBR can be used to clinically treat hypertrophic scars and, more generally, fibrotic diseases.

Assessing keloid treatment efficacy: a comparison of intralesional umbilical-cord mesenchymal stem cells, their conditioned medium, and triamcinolone acetonide injection through macroscopic and microscopic examination

Link Video Abstract: https://youtu.be/NAnsqP7dPd0 Background: Current keloid treatment involves intralesional injection of triamcinolone acetonide (TA), which, despite its usage, is associated with high recurrence rates and adverse effects. Mesenchymal stem cells (MSCs) exhibit potent proliferative abilities and can curb fibroblast activity and proliferation within keloids. It is now known that umbilical cord mesenchymal stem cells (UC-MSCs) have been shown to have greater proliferative potential than bone marrow-derived MSCs (BM-MSCs), and other advantages of UC-MSCs include being easily accessible and less immunogenic. To assess the viability of administering umbilical cord MSC (UC-MSC) and its conditioned medium (UC-CM) via intralesional injection compared to TA in reducing macroscopic keloid volume and type 1:3 collagen ratio. Methods: This randomized controlled trial enrolled twenty-four keloid patients by consecutive sampling. Eligible patients were required to have keloids on the chest, back, abdomen, or extremities. Patients with hypertrophic scars, a history of kidney failure, hypertension, blood disorders, malignancy, pregnancy, breastfeeding, or keloid treatment were excluded. Sociodemographic data, keloid size, and tissue biopsies were collected during scheduled visits. Bivariate analyses applied were considered significant at a p-value of &lt;0.05. Results: The study revealed that the most significant decrease in macroscopic volume occurred within the UC-MSC group, followed by the UC-CM group, and then the TA group (UC-MSC: 50.24% ± 3.58%; UC-CM: 43.97% ± 3.04%; TA: 33.53% ± 2.64; p = 0.004. The UC-CM group exhibited the most substantial decrease in the type 1:3 collagen ratios (4.80±0.26), with UC-MSC (4.60(4.15-8.05)) and TA (3.96(1.63-4.14)) following in sequence (p=0.002). Conclusion: The findings of this study indicate that the use of UC-MSC and UC-CM exhibits promising superiority over TA in terms of reducing macroscopic keloid volume and type 1:3 collagen ratio.

Autocrine IL-6 drives cell and extracellular matrix anisotropy in scar fibroblasts

Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a globally aligned ECM network in 2-D culture as observed in scar tissue. ECM anisotropy develops after rapid initiation of a fibroblast supracellular actin network, suggesting that cell alignment initiates ECM patterning. Keloid fibroblasts produce elevated levels of IL-6, and autocrine IL-6 production is both necessary and sufficient to induce cell and ECM alignment, as evidenced by ligand stimulation of normal dermal fibroblasts and treatment of keloid fibroblasts with the function blocking IL-6 receptor monoclonal antibody, tocilizumab. Downstream of IL-6, supracellular organization of keloid fibroblasts is controlled by activation of cell-cell adhesion. Adhesion formation inhibits contact-induced cellular overlap leading to nematic organization of cells and an alignment of focal adhesions. Keloid fibroblasts placed on isotropic ECM align the pre-existing matrix, suggesting that focal adhesion alignment leads to active anisotropic remodeling. These results show that IL-6-induced fibroblast cooperativity can control the development of a nematic ECM, highlighting both IL-6 signaling and cell-cell adhesions as potential therapeutic targets to inhibit this common feature of fibrosis.

The Role of &lt;i&gt;Ayurveda Kshara Karma&lt;/i&gt; in the Management of &lt;i&gt;Keloid&lt;/i&gt;: A Case Study

Keloids, the benign dermal fibro-proliferative nodular lesions, which often tend to cause socio-economic and psycho-somatic stress pose a major challenge to clinicians till date. Apprehending and analyzing keloids under the concept of Vranagranthi described in the ancient science of Ayurveda and amalgamating the therapeutic principles explained in the classics can emerge as a ray of hope in the condition. Kshara karma (chemical cauterization) is an important para-surgical procedure which can be effectively incorporated into the treatment of wounds, Keloids and hypertrophic scars. An 18-year-old client who presented with overgrowth of scar tissue at the right anterolateral part of the chest region was treated at the OPD of the Division of Ayurveda, MAHE, Manipal. Kshara karma, which included the painting of Teekshna Apamarga kshara (ashes of Achyranthes aspera) for a duration of 100 Matra kala (approximately 2 mins), in two sittings brought about total regression of the Vranagranthi and the associated symptoms. No signs of recurrence were noticed during the follow-ups. Thus, Kshara karma can emerge as a promising solution in the stress-filled life of Keloid patients.

An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid

Background: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated. Objectives: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients. Methods: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro. Results: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway. Conclusion: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.

Association Between Sebum, Total Cholesterol, and Low-Density Lipoprotein (LDL) Cholesterol Levels With Post-acne Keloids.

Background Prolonged acne inflammation causes scar formation, one of which is post-acne keloids. Sebum, total cholesterol, and low-density lipoprotein (LDL) level can influence post-acne keloids. This study aims to determine the association between sebum, total cholesterol, and LDL levels with post-acne keloids to better define the predisposing factors for this condition. Methods This study used primary data involving sociodemographics, clinical features, keloid classification, sebum levels, total cholesterol levels, and LDL levels in post-acne keloid patients at the Dermatology, Venereology, and Aesthetics Outpatient Clinics of Dr. Mohammad Hoesin General Hospital Palembang, Indonesia. Study samples were patients who fulfilled the inclusion and exclusion criteria by consecutive sampling. The data then underwent univariate and bivariate analyses to show the association between variables. Result A total of 22 patients with post-acne keloids participated. The subjects presented mostly with major keloids based on the classification (59.1%). The patients were predominantly 21-30 years old (50%) and male (90.9%). The keloids had onsets >six months to one year (45.5%), durations of one to five years (77.3%), and multiple presentations (68.2%). Vancouver Scar Scale (VSS) assessment showed mainly red vascularity (40.9%), mixed pigmentation (68.2%), >5 mm keloid height (59.1%), and firm pliability (40.9%). Most patients presented with pruritus (86.4%) but without pain (54.5%). Most had low levels of sebum (50%), normal total cholesterol (90.9%), and near-optimal LDL level (40.9%). There were no significant association between sebum (p = 1.000), total cholesterol (p = 1.000), and LDL (p = 0.376) levels with post-acne keloids. However, LDL levels above normal were most found in this study (68.2%). Conclusions There is no association between sebum, total cholesterol, and LDL levels with post-acne keloids. Despite the fact that LDL level was not statistically significant, there has been a rise in LDL level in the research subjects. Further research with a larger number of subjects and consideration of multicenter study through retrospective/prospective methods and complete lipid profile examinations is still required to provide a more representative study.

Establishment of a humanized mouse model of keloid diseases following the migration of patient immune cells to the lesion: Patient-derived keloid xenograft (PDKX) model

Keloid disorder is an abnormal fibroproliferative reaction that can occur on any area of skin, and it can impair the quality of life of affected individuals. To investigate the pathogenesis and develop a treatment strategy, a preclinical animal model of keloid disorder is needed. However, keloid disorder is unique to humans, and the development of an animal model of keloid disorder is highly problematic. We developed the patient-derived keloid xenograft (PDKX), which is a humanized mouse model, and compared it to the traditional mouse xenograft model (transplantation of only keloid lesions). To establish the PDKX model, peripheral mononuclear cells (PBMCs) from ten keloid patients or five healthy control subjects were injected into NOD/SCID/IL-2Rγnull mice, and their keloid lesions were grafted onto the back after the engraftment of immune cells (transplantation of keloid lesions and KP PBMCs or HC PBMCs). Four weeks after surgery, the grafted keloid lesion was subjected to histologic evaluation. Compared to the traditional model, neotissue formed along the margin of the grafted skin, and lymphocyte infiltration and collagen synthesis were significantly elevated in the PDKX model. The neotissue sites resembled the margin areas of keloids in several respects. In detail, the levels of human Th17 cells, IL-17, HIF-1a, and chemokines were significantly elevated in the neotissue of the PDKX model. Furthermore, the weight of the keloid lesion was increased significantly in the PDKX model, which was due to the proinflammatory microenvironment of the keloid lesion. We confirmed that our patient-derived keloid xenograft (PDKX) model mimicked keloid disorder by recapitulating the in vivo microenvironment. This model will contribute to the investigation of cellular mechanisms and therapeutic treatments for keloid disorders.

Clinical Effects of Pulsed Dye Laser Dynamically Combined with Triamcinolone Acetonide in the Treatment of Postoperative Recurrence Keloids.

This study aimed to explore the clinical effects of pulsed dye laser (PDL) dynamically combined with triamcinolone acetonide (TAC) in the treatment of post-operative keloids recurrence. This study retrospectively analysed the clinical data of 29 keloid patients (with 39 keloids) from April 2014 to February 2020. The patients were divided into TAC group (14 patients with 19 keloids) and dynamic treatment group (15 patients with 20 keloids) according to the post-operative treatment that they received. The keloids were assessed by Vancouver scar scale (VSS), patient and observer scar assessment scale (POSAS) and the effect of keloids on the quality of life of patients was evaluated with dermatology life quality index (DLQI) scale before the surgical treatment, at any time of relapse, and 24 months after the surgical treatment. The recurrence-free interval, relative cure time, and the cumulative times of TAC injection when the relative cure could be assessed as achieved, and the incidence of adverse reactions were calculated. Patients experiencing a recurrence within 2 years after surgery included 19 keloids (25.33%) that developed a recurrent event within 6 months, 34 keloids (45.33%) that within 12 months, and 39 keloids (52.00%) that within 24 months after surgery. Anterior chest keloid had the highest recurrence rate and ear keloid had the lowest recurrence rate. The total pigmentation and vascularity (VSS and POSAS) scores of patients' keloids in TAC group and dynamic treatment group 24 months after treatment were significantly lower than those before treatment and at relapse (P < 0.05), the total VSS and POSAS scores were significantly lower at 24 months than before treatment and at relapse (P < 0.05), and the DLQI scale score was significantly lower at 24 months than before treatment (P < 0.05). The VSS and POSAS scores of patients' keloids at 24 months after treatment were significantly lower in the dynamic treatment group than in the TAC group. The relative cure time of patients' keloids in the dynamic treatment group was 6.47 ± 2.72 months, which was significantly shorter than 8.65 ± 3.67 months in the TAC group (P < 0.05). The cumulative number of TAC injections that were given to achieve a relative cure of patients' keloids in dynamic treatment group was 3.60 ± 1.76, which was significantly less than 5.24 ± 2.25 in TAC group. The total incidence of adverse reactions was lower in the dynamic group than in TAC group, but this difference did not reach statistical significance (P > 0.05). Compared with TAC injection alone, PDL dynamically combined with TAC in the treatment of keloid with post-operative recurrence can shorten the relative cure time, reduce the number of TAC injections and improve the clinical efficacy.

2-Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway.

The MAPK/Erk signaling pathway is a classic pathway in cell proliferation. Our former study showed that keloid tissue revealed a higher proliferation level than physiological scars and normal skin. As a natural metabolite of estradiol, 2-methoxyestradiol (2ME2) showed an inhibition proliferation effect on tumor cells. In this study, the treatment effect of 2ME2 and its potential mechanisms are explored. Six keloid patients and six non-keloid patients were randomly selected from the Department of Plastic Surgery at our hospital during June 2021 to December 2021. Six groups were established: normal skin fibroblasts (N); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (K + 2ME2); keloid fibroblasts treated with dimethyl sulfoxide (DMSO) (K + DMSO); keloid fibroblasts treated with doramapimod (K + IN); keloid fibroblasts treated with doramapimod (p38 inhibitor) and 2ME2 (K + IN+2ME2). The fibroblast activity and key factor expression of the MAPK/Erk signaling pathway were measured. In the results, 2ME2 significantly inhibited keloid fibroblast activity and key factor expression (except STAT1). The proliferation levels were reduced by both the p38 inhibitor and 2ME2, indicating 2ME2 may achieve an antiproliferation effect by targeting p38 in keloid fibroblasts.

Limitation of Jalauka (medicinal leech) application in the prevention of recurrence of keloid

Keloid can be defined as a benign dermal fibroproliferative disorder with no malignant potential. The keloids tend to occur following trivial physical trauma in genetically predisposed individuals. Jalauka (medicinal leech, Hirudo medicinalis) is famed to use in all skin disorders caused by vitiation of Rakta (~blood) and Pitta Dosha (a functional regulatory factor of the body). Many studies also have claimed that the saliva of medicinal leeches potentiates wound healing. It helps in healthy scar formation by inhibiting the conversion of fibrinogen to fibrin. Therefore, a hypothesis was made that medicinal leech application can be helpful in the healing of the wound without keloid formation in patients with keloid formation tendencies. In the present study, case of a 38-year-old male patient infected sebaceous cyst at the right upper back (scapular region) with a previous history of keloid formation after surgical scar was treated by weekly medicinal leech application five times after excision of the cyst under local anesthesia. Initiation wound healing was normal in the studied case until complete epithelization. After 2 months of complete healing, gradual hardening and shiny appearance with irregular margin became very prominent and seemed to convert in keloid, although other associated symptoms were absent. The findings of this case report indicate the limited effect of the medicinal leech application and the requirement of a multimodel therapeutic approach for healthy wound healing in keloid tendency patients.

Bioinformatics analysis and verification of m6A related genes based on the construction of keloid diagnostic model.

Keloids are formed due to abnormal hyperplasia of the skin connective tissue. We explored the relationship between N6-methyladenosine (m6A)-related genes and keloids. The transcriptomic datasets (GSE44270 and GSE185309) of keloid and normal skin tissues samples were obtained from the Gene Expression Omnibus database. We constructed the m6A landscape and verified the corresponding genes using immunohistochemistry. We extracted hub genes for unsupervised clustering analysis using protein-protein interaction (PPI) network; gene ontology enrichment analysis was performed to determine the biological processes or functions affected by the differentially expressed genes (DEGs). We performed immune infiltration analysis to determine the relationship between keloids and the immune microenvironment using single-sample gene set enrichment analysis and CIBERSORT. Differential expression of several m6A genes was observed between the two groups; insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was significantly upregulated in keloid patients. PPI analysis elucidated six genes with significant differences between the two keloid sample groups. Enrichment analysis revealed that the DEGs were mainly enriched in cell division, proliferation, and metabolism. Moreover, significant differences in immunity-related pathways were observed. Therefore, the results of this study will provide a reference for the elucidation of the pathogenesis and therapeutic targets of keloids.

A retrospective study on the association of keloids with underlying health conditions in African-American Women.

This study aims to identify whether there is any association of keloids with underlying health conditions in African-American women. This study was done via the use of the National Inpatient Sample, a subset of the Healthcare Cost and Utilization Project. African-American women with keloids who had undergone cesarean sections were compared with a control group of African-American women with no history of keloids who had undergone cesarean sections. A total of 301 African-American inpatient encounters with patients with keloids were compared with 37,144 encounters in the control group. The keloid patients had an increased association with peritoneal adhesions compared with the control group. results are limited to one race and restricted age range; also, unable to differentiate keloids from hypetrophic scarring with ICD-10 codes. These findings suggest that keloids and peritoneal adhesions may have similar inflammatory processes.

Risk factors associated with keloid infections: A five-year retrospective study.

Keloid infections reduce patient-reported quality of life greatly. Characteristics and risk factors of keloid infections have not been thoroughly studied. So, a retrospective cohort study was conducted focusing on the potential risk factors, microbiologic cultures and histological findings. Keloid patients consulting for surgical interventions were included in this study. Data were collected from their electronic medical records. 564 patients were recruited with the keloid infection rate being 22.4%. For adult patients, age above 40 years (OR, 2.84; P= .000), disease duration of 12 years or more (OR, 3.03; P= .000), the number of keloids over 3 (OR, 1.59; P= .050) and the presence of family history (OR, 1.91; P= .027) were significantly associated with keloid infections. Suppurative keloids were located mostly in thorax (61.79%). For the under-age subgroup(n=25), family history was frequently seen in patients with infections. Microbiologic cultures revealed a mixed spectrum of bacteria including Staphylococcus (25%), Actinomyces (30%) and Prevotella (10%). The rate of epidermoid cysts was 19.7% in histological examination. Age > 40 years, disease duration ≥12 years, the number of keloids >3 and the presence of family history are risk factors for keloid infections.

Keloid Patient Plasma-Derived Exosomal hsa_circ_0020792 Promotes Normal Skin Fibroblasts Proliferation, Migration, and Fibrogenesis via Modulating miR-193a-5p and Activating TGF-β1/Smad2/3 Signaling.

Keloids are fibroproliferative disorders, which seriously affect the quality of life of patients with keloids. Additionally, circRNAs are enriched within exosomes derived from human blood samples, whereas their relationship with keloids remains largely unknown. It has been reported that hsa_circ_0020792 was abnormally upregulated in keloid tissues. However, the role of keloid patient plasma-derived exosomal hsa_circ_0020792 in the formation and development of keloids is not well understood. Exosomes were isolated from the peripheral blood plasma of the patients with keloids (keloid patient-Exo) and healthy controls (Healthy control-Exo). The hsa_circ_0020792 and miR-193a-5p levels in keloid patient-Exo and healthy control-Exo, as well as in keloid fibroblasts and normal skin fibroblasts (NFs) were evaluated by RT-qPCR. The level of hsa_circ_0020792 was remarkably increased in keloid patient-Exo and keloid fibroblasts compared with that in Healthy control-Exo and NFs, respectively. In addition, keloid patient-Exo obviously enhanced the viability, migration, and extracellular matrix (ECM) synthesis, but reduced the apoptosis of NFs. Moreover, keloid patient-Exo notably promoted the fibrogenesis of NFs, as characterized by enhanced TGF-β signaling, increased expressions of phosphorylated Smad2/3. However, downregulation of hsa_circ_0020792 markedly reversed the promoting effects of keloid patient-Exo on cell growth, migration, and myofibroblast activation and fibrogenesis. Furthermore, downregulation of hsa_circ_0020792 significantly reduced the viability, migration, and fibrogenesis in NFs, whereas these phenomena were reversed by miR-193a-5p inhibitor. Collectively, keloid patient plasma-derived exosomal hsa_circ_0020792 could promote the proliferation, migration, and fibrogenesis of NFs via modulating miR-193a-5p and activating TGF-β1/Smad2/3 signaling.

Invariant chain of the MAIT-TCR vα7.2-Jα33 as a novel diagnostic biomarker for keloids.

Keloids are pathological scars that invade normal surrounding tissue without self-limitation, causing pain, itching, cosmetic disfigurement, etc. Knowledge of the molecular mechanisms underlying keloids remains unclear; thus, there are no available biomarkers for its diagnosis, resulting in a diagnostic accuracy of only 81%, which may be resolved by seeking an effective biomarker. Given that keloids possess pathogenic features similar to those of autoimmune skin disease, this study aimed to utilise the single-cell V(D)J sequencing method to identify a potential biomarker and clarify the underlying biological mechanisms. Single-cell V(D)J sequencing was used to detect T cell receptor (TCR) diversity between keloid patients and healthy donors using peripheral blood samples, the results of which were further validated using reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry was used to analyse the mucosal-associated invariant T (MAIT) cell percentage, cytokine production, and activation marker expression levels in peripheral blood samples of keloid patients and normal donors. An immunofluorescence test was used to quantitatively analyse the distribution of MAIT cells in scar and healthy donor skin tissues. Single-cell V(D)J sequencing analysis showed that the usage frequency of the TRAJ33-one invariant chain of the TCR of MAIT cells was decreased in keloid patients. This result was validated by RT-PCR, which showed that significantly lower TCR Vα7.2-Jα33 was expressed in keloid patients compared with that in healthy donors and hypertrophic scar patients (p < 0.05). Flow cytometry and immunofluorescence tests further verified that MAIT cells decreased significantly both in the peripheral blood sample and lesions of keloid patients compared with those of healthy controls (p < 0.05). MAIT cells from keloid patients secreted less interferon (IFN)-γ than those from the healthy controls and hypertrophic scar group (p < 0.001). The percentage of PLZF+ MAIT cells was lowest in the peripheral blood samples of keloid patients (p < 0.05). The percentage of IL-18+ MAIT cells was lower in the peripheral blood samples of keloid patients compared with that in healthy donors (p < 0.05). These findings indicate that MAIT cells could be associated with keloids and may serve as potential biomarkers or therapeutic targets in the diagnosis of keloids.

Lesion Site Is the Key Prognostic Factor for Keloid Patients Receiving Surgery With Adjuvant Radiotherapy.

Keloid is a benign tumor with high recurrence rate; accordingly, complete surgical excision with adjuvant radiotherapy is one of the most effective treatments. This study reviewed outcomes of keloid patients receiving surgery and adjuvant radiotherapy in Kaohsiung Medical University Hospital. All patients received radiation dose with 15 Gy, with their first radiotherapy within 24 hours after surgical excision. The end points were recurrence rate and local recurrence-free interval (LRFI), defined clinically as palpable gross tumor over the treatment site and duration from the last day of radiotherapy to disease recurrence. From May 2017 to July 2020, 32 patients with 40 keloid lesions were included. The mean age for these patients was 37.6 years, and the median follow-up time was 15.3 months. The overall recurrence rate was 52.5%, and the median LRFI was 9.7 months. Recurrence rates for males and females were 46.7% and 56% ( P = 0.567), respectively; for head and ear, chest, shoulder and upper extremities, and abdomen and back were 12.5%, 61.5%, 63.6%, and 62.5% ( P = 0.093); for lesions over 20 cm 2 and below 20 cm 2 were 62.5% and 50% ( P = 0.527); and for megavoltage electron beam and kilovoltage photon beam were 56.7% and 40% ( P = 0.361), respectively. Patients were further classified into 2 groups by lesion sites, which showed lower recurrence rate ( P = 0.011) and longer LRFI ( P = 0.028) with lesions over the head and ear than other sites. We found that lesion site might be a prognostic factor for keloid recurrence. Adjuvant radiation dose escalation for high-recurrence risk areas (other than the head and ear) might be required.

Serum long non Coding RNA in keloid patients A Systematic Review and Meta-analysis

Serum long non Coding RNA in keloid patients A Systematic Review and Meta-analysis