• Cancer formation
• Diagnosis
• Keloid
• Mechanism
• Personalized treatment

• Botulinum toxin
• Clinical trial
• Efficacy
• Hypertrophic scar
• Keloid
• Pulsed dye laser
• Safety
• Triamcinolone

• Humans
• Botulinum Toxins, Type A/therapeutic use
• Botulinum Toxins, Type A/administration & dosage
• Botulinum Toxins, Type A/adverse effects
• Female
• Male
• Adult
• Keloid/therapy
• Keloid/drug therapy
• Cicatrix, Hypertrophic/therapy
• Cicatrix, Hypertrophic/drug therapy
• Single-Blind Method
• Lasers, Dye/therapeutic use
• Lasers, Dye/adverse effects
• Combined Modality Therapy
• Triamcinolone/therapeutic use
• Triamcinolone/administration & dosage
• Young Adult
• Low-Level Light Therapy/methods
• Low-Level Light Therapy/adverse effects
• Treatment Outcome
• Middle Aged

• Cryotherapy
• Hypertrophic scar
• Keloid
• Pulsed dye laser
• Triamcinolone acetonide

• Bleomycin
• Hypertrophic scar
• Intralesional
• Triamcinolone Acetonide

• Humans
• Cicatrix, Hypertrophic/drug therapy
• Cicatrix, Hypertrophic/pathology
• Network Pharmacology/methods
• Drug Discovery
• Dermatologic Agents/pharmacology
• Dermatologic Agents/therapeutic use

• Fibrosis
• IL-17
• Immunotherapy
• Keloid
• Pathogenesis
• Th17

• Humans
• Interleukin-17/metabolism
• Interleukin-17/immunology
• Keloid/drug therapy
• Keloid/immunology
• Keloid/pathology
• Signal Transduction/drug effects
• Signal Transduction/immunology
• Skin/pathology
• Skin/immunology
• Th17 Cells/drug effects
• Th17 Cells/immunology
• Th17 Cells/metabolism

• Hypertrophic scar
• Preclinical model
• Scar prevention
• Skin biology

• Animals
• Rabbits
• Cicatrix, Hypertrophic/pathology
• Cicatrix, Hypertrophic/etiology
• Cicatrix, Hypertrophic/prevention & control
• Cicatrix, Hypertrophic/surgery
• Disease Models, Animal
• Minimally Invasive Surgical Procedures/methods
• Minimally Invasive Surgical Procedures/adverse effects
• Ear/surgery
• Ear/pathology
• Ischemia/etiology
• Ischemia/surgery
• Ischemia/pathology
• Humans
• Wound Healing
• Suture Techniques

• adult
• child
• humans
• burns
• burns/complications
• burns/therapy
• cicatrix
• cicatrix/etiology
• cicatrix/prevention & control
• lanolin
• pain
• pruritus
• pruritus/etiology
• pruritus/prevention & control
• silicone gels
• silicone gels/therapeutic use

• Adult
• Child
• Humans
• Cicatrix/etiology
• Cicatrix/prevention & control
• Lanolin
• Silicone Gels/therapeutic use
• Burns/complications
• Burns/therapy
• Pain
• Pruritus/etiology
• Pruritus/prevention & control

• Hypertrophic scar
• Zr-MOF-808
• alpha-smooth muscle actin (α- SMA)
• metal-organic frameworks (MOF)
• myofibroblasts
• silicone patch
• transforming growth factor β1 (TGF- β1)

• Animals
• Rabbits
• Cicatrix, Hypertrophic/metabolism
• Cicatrix, Hypertrophic/pathology
• Metal-Organic Frameworks/metabolism
• Metal-Organic Frameworks/pharmacology
• Fibroblasts
• Collagen Type I/metabolism
• Collagen Type I/pharmacology
• Collagen/metabolism
• Transforming Growth Factor beta1/metabolism
• Transforming Growth Factor beta1/pharmacology

• Cell-free therapy
• ESCRT pathway
• extracellular vesicles
• melanocytes.
• negative zeta potential
• therapeutic nanovesicles

• Humans
• Extracellular Vesicles/metabolism
• Exosomes/metabolism
• Skin
• Cell Communication
• RNA

• 29232 Shahid Beheshti University of Medical Sciences

• Hypertrophic scars
• Intralesional
• Keloids
• Triamcinolone

• Humans
• Keloid/drug therapy
• Cicatrix, Hypertrophic/drug therapy
• Triamcinolone/therapeutic use
• Treatment Outcome
• Fluorouracil

• Humans
• Keloid/pathology
• Cicatrix, Hypertrophic/pathology
• Skin/pathology
• Wound Healing
• Fibrosis

• 595 nm dye-laser
• CO2 laser therapy
• dark subjects
• earlobe keloids

• Male
• Humans
• Female
• Young Adult
• Adult
• Ear, External/surgery
• Keloid/radiotherapy
• Keloid/surgery
• Carbon Dioxide
• Laser Therapy
• Recurrence
• Treatment Outcome

• immune cells
• immunotherapy
• keloid
• keloid microenvironment
• keloid pathogenesis
• keloid treatment
• monoclonal antibody

• Humans
• Keloid/metabolism
• Quality of Life
• Collagen/metabolism
• Fibroblasts/metabolism
• Cells, Cultured
• Immunotherapy
• Communication

• 82272294 National Natural Science Foundation of China
• 2022-RC320-02 Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences

• Humans
• Keloid/surgery
• Keloid/drug therapy
• Dermatologists
• Adrenal Cortex Hormones/therapeutic use
• Surveys and Questionnaires
• Surgeons
• Treatment Outcome

• adults
• hypertrophic scars
• keloid
• paediatric
• real-world
• scar prevention
• scar treatment
• topical silicone gel

• comprehensive treatment
• ear keloid
• radiotherapy

• Female
• Humans
• Young Adult
• Adult
• Keloid/etiology
• Keloid/surgery
• Combined Modality Therapy
• Triamcinolone
• Ear Auricle/surgery
• Injections, Intralesional
• Treatment Outcome
• Recurrence

• cutaneous infections
• dermatological conditions
• inflammatory skin disease
• military medicine
• military readiness
• occupational skin disease
• operational dermatology
• skin cancer
• teledermatology
• teledermoscopy

• Dermal fibrosis
• Mechanotransduction
• Pressure therapy
• Skin biomechanics
• Tension therapy
• Wound healing

Keloids are pathologic wound healing conditions caused by fibroblast hyperproliferation and excess collagen deposition following skin injury or irritation, which significantly impact patients by causing psychosocial and functional distress. Extracellular matrix (ECM) deposition and human fibroblast proliferation represents the main pathophysiology of keloid. Long non-coding RNAs (LncRNAs) play important roles in many biological and pathological processes, including development, differentiation and carcinogenesis. Recently, accumulating evidences have demonstrated that deregulated lncRNAs contribute to keloids formation. The present review summarizes the researches of deregulated lncRNAs in keloid. Exploring lncRNA-based methods hold promise as new effective therapies against keloid.

Hypertrophic scarring (HS), caused by excessive fibrosis of injured skin, imposes a psychological burden and creates a source of distress that impairs the quality of life of affected individuals. However, the gold standard for HS treatment has not yet been determined due to the complicated and difficult nature of the routines and procedures involved. Previous studies have indicated that the topical application of certain active components found in traditional Chinese medicines shows potential as a therapeutic alternative for scars. Here, single-cell RNA-sequencing was performed to determine cellular heterogeneity and identify marker genes and mechanisms associated with HS. It was found that fibroblasts comprise the largest proportion of HS cell types. The marker genes that were highly expressed in fibroblasts were extracellular matrix (ECM)-related, whereas ECM-receptor interactions and the transforming growth factor (TGF)-β signalling pathway were also found to be active. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, which was applied to identify the molecular compounds of Dispel-Scar Ointment (DSO), revealed 74 effective chemical components belonging to 14 types of constituents, such as flavonoids, tanshinones, salvianolic acids, glycosides, and phthalides. Furthermore, in vivo studies using rat scar models showed that the topical application of Salvia miltiorrhiza, Ligusticum chuanxiong, peach kernel, safflower, and motherwort exerted beneficial effects on fibroblasts. DSO promoted scar maturation and reduced scar areas, its efficacy being similar to that of topically applied silicone. Functional studies using immunofluorescence staining, western blotting, and quantitative real-time polymerase chain reaction demonstrated that DSO may target the TGF-β/Smad pathway to inhibit collagen synthesis and promote ECM remodelling. However, further in vitro mechanistic research and single-drug prescription studies may be required to identify the specific effective compound or active ingredient of DSO, which would provide more substantial evidence regarding the potential therapeutic value of traditional herbs in HS.

Objective: This work aimed to verify the candidate biomarkers for keloid disorder (KD), and analyze the role of immune cell infiltration (ICI) in the pathology of keloid disorder.

Methods: The keloid-related datasets (GSE44270 and GSE145725) were retrieved from the Gene Expression Omnibus (GEO). Then, differential expressed genes (DEGs) were identified by using the “limma” R package. Support vector machine-recursive feature elimination (SVM-RFE) and LASSO logistic regression were utilized for screening candidate biomarkers of KD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of candidate biomarkers. The candidate biomarkers were further verified through qRT-PCR of keloid lesions and the matched healthy skin tissue collected from eight cases. In addition, ICI in keloid lesions was estimated through single-sample gene-set enrichment analysis (ssGSEA). Finally, the potential drugs to the treatment of KD were predicted in the Connectivity Map Database (CMAP).

Results: A total of 406 DEGs were identified between keloid lesion and healthy skin samples. Among them, STC2 (AUC = 0.919), SDC4 (AUC = 0.970), DAAM1 (AUC = 0.966), and NOX4 (AUC = 0.949) were identified as potential biomarkers through the SVM-RFE, LASSO analysis and ROC analysis. The differential expressions of SDC4, DAAM1, and NOX4 were further verified in collected eight samples by qRT-PCR experiment. ICI analysis result showed a positive correlation of DAAM1 expression with monocytes and mast cells, SDC4 with effector memory CD4⁺ T cells, STC2 with T follicular helper cells, and NOX4 with central memory CD8⁺ T cells. Finally, a total of 13 candidate small molecule drugs were predicted for keloids treatment in CMAP drug database.

Conclusion: We identified four genes that may serve as potential biomarkers for KD development and revealed that ICI might play a critical role in the pathogenesis of KD.

Backgroundand Objectives: Hypertrophic scars following surgeries or burns present a serious concern for many patients because these scars not only lead to an aesthetical but also to a functional and psychological burden. Treatment of hypertrophic scars is challenging because despite various treatment options, a low level of evidence hinders preference of any specific treatment plan. To properly identify new therapeutic approaches, the use of in vivo models remains indispensable. A gold standard for hypertrophic scars has not been established to date. This review aims at giving a comprehensive overview of the available in vivo models. Materials and Methods: PubMed and CINAHL were queried for currently existing models. Results: Models with mice, rats, rabbits, pigs, guinea pigs and dogs are used in hypertrophic scar research. Rodent models provide the advantage of ready availability and low costs, but the number of scars per animal is limited due to their relatively small body surface, leading to a high number of test animals which should be avoided according to the 3Rs. Multiple scars per animal can be created in the guinea pig and rabbit ear model; but like other rodent models, these models exhibit low transferability to human conditions. Pig models show a good transferability, but are cost-intensive and require adequate housing facilities. Further, it is not clear if a currently available pig model can deliver clinical and histological features of human hypertrophic scars concurrently. Conclusions: None of the analyzed animal models can be clearly recommended as a standard model in hypertrophic scar research because the particular research question must be considered to elect a suitable model.

• Animals
• Burns
• Cicatrix, Hypertrophic/drug therapy
• Cicatrix, Hypertrophic/etiology
• Disease Models, Animal
• Dogs
• Guinea Pigs
• Humans
• Mice
• Rabbits
• Rats
• Wound Healing

Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients’ quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids.

In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients’ interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids.

Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration > 15 years (OR, 2.98; P = 0.046).

Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration > 15 years.

Asthma is a common chronic respiratory disease that influences 300 million people all over the world. However, the pathogenesis of asthma has not been fully elucidated. It has been reported that transforming growth factor-β (TGF-β) can activate myofibroblasts. Moreover, the fibroblast to myofibroblast transformation (FMT) can be triggered by TGF-β, which is a major mediator of subepithelial fibrosis. Secreted modular calcium-binding protein 2 (SMOC2) is a member of cysteine (SPARC) family and is involved in the progression of multiple diseases. However, its role in asthma remains poorly understood. RT-qPCR evaluated the expression of SMOC2. Bromodeoxyuridine assay and wound-healing assay detected the proliferation and migration of lung fibroblasts, respectively. IF staining was performed to assess the expression of α-smooth muscle actin (α-SMA). Western blot analysis detected the levels of proteins. Flow cytometry was utilized for determination of the number of myofibroblasts.

We found the expression of SMOC2 was upregulated by the treatment of TGF-β1 in lung fibroblasts. In addition, SMOC2 promoted the proliferation and migration of lung fibroblasts. More importantly, SMOC2 accelerated FMT of lung fibroblasts. Furthermore, SMOC2 was verified to control the activation of AKT and ERK. Rescue assays showed that the inhibition of AKT and ERK pathway reversed the promoting effect of SMOC2 overexpression on proliferation, migration and FMT in lung fibroblasts.

This work demonstrated that SMOC2 modulated TGF-β1-induced proliferation, migration and FMT in lung fibroblasts and may promote asthma, which potentially provided a novel therapeutic target for the management of asthma.

The online version contains supplementary material available at 10.1186/s41065-021-00213-w.

• Asthma
• Lung fibroblasts
• Myofibroblast transformation
• SMOC2
• TGF-β1

• Keloids
• Photoacoustic imaging
• Ultrasound
• Vancouver Scar Scale

• T lymphocytes
• immunity
• keloid
• macrophages
• signal transduction

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998–2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

Keloid disease is hard to fully eradicate. Recurrence and other unsatisfactory results were found in many patients. No current therapeutic modality has been determined to be most effective for treating keloid scars. Intralesional corticosteroid injections is most commonly recommended for primary management of small and young keloids as well as hypertrophic scars. However, it’s difficult for patients to adhere to long-term triamcinolone acetonide injection therapy because of the pain, inconvenience or complications including hormonal imbalance or irregular menstruation.

We aimed to determine whether and how Strontium-90 brachytherapy as an adjuvant radiation could affect keloid recurrence after intralesional triamcinolone and 5-fluorouracil injections.

We included keloid patients from March 2019 to September 2019 and randomly allocated them to two groups after 3 intralesional triamcinolone and 5-fluorouracil injections at 3 weeks interval. The experimental group received Strontium-90 brachytherapy at a total dose of 15-20Gy, while the control group didn’t receive any adjuvant treatment. We performed both Vancouver Scar Scale scoring and Color Doppler ultrasound examination to monitor and evaluate lesions regularly. A one-year follow-up was completed for each patient.

31 patients who had 42 keloids in total were recruited. We found intralesional triamcinolone and 5-fluorouracil injections could effectively reduce the thickness and modify the hardness of small and young keloids. Strontium-90 brachytherapy reduced the one-year recurrence rate from 85.7 percent to 44.4 percent after 3 intralesional triamcinolone and 5-fluorouracil injections. The lesions’ thickness or elasticity was not affected by Strontium-90 brachytherapy.

Strontium-90 brachytherapy as an adjuvant radiation could effectively reduce small sized keloids recurrence after intralesional triamcinolone and 5-fluorouracil injections. It worked by enhancing the lesions’ stability post-injection.

The clinical trial registration number: ChiCTR2000030141.

Name of trial registry: Chinese Clinical Trial Registry (http://www.chictr.org.cn/)

• Adult
• Brachytherapy
• Elastic Modulus
• Elasticity Imaging Techniques
• Female
• Fluorouracil/therapeutic use
• Humans
• Injections, Intralesional
• Keloid/diagnostic imaging
• Keloid/drug therapy
• Keloid/physiopathology
• Keloid/radiotherapy
• Male
• Recurrence
• Strontium Radioisotopes/therapeutic use
• Triamcinolone Acetonide/therapeutic use
• Young Adult

• National Natural Science Foundation of China

• Granulomatous disease
• auxiliary treatment
• case report
• cutaneous sarcoidosis
• laser therapy
• pulsed-dye laser

Keloids are characterized by disturbance of fibroblast proliferation and apoptosis, deposition of collagen, and upregulation of dermal inflammation cells. This benign dermal fibro-proliferative scarring condition is a recognized skin inflammation disorder. Chronic inflammation is a well-known contributor to bone loss and its sequelae, osteoporosis. They both shared a similar pathogenesis through chronic inflammation. We assessed whether keloids increase osteoporosis risk through using National Health Insurance Research Database.

The 42,985 enrolled patients included 8597 patients with keloids but no history of osteoporosis; 34,388 controls without keloids were identified from the general population and matched at a one-to-four ratio by age, gender. Kaplan-Meier method was applied to determine cumulative incidence of osteoporosis. Cox proportional hazard regression analysis was performed after adjustment of covariates to estimate the effect of keloids on osteoporosis risk.

Of the 8597 patients with keloids, 178 (2.07%) patients were diagnosed with osteoporosis while in the 34,388 controls, 587 (1.71%) were diagnosed with osteoporosis. That is, the keloids patients had 2.64-fold higher risk of osteoporosis compared to controls after adjustment for age, gender, Charlson Comorbidity Index and related comorbidities. The association between keloids and osteoporosis was strongest in patients younger than 50 years (hazard ratio = 7.06%) and in patients without comorbidities (hazard ratio = 4.98%). In the keloids patients, a high incidence of osteoporosis was also associated with advanced age, high Charlson Comorbidity Index score, hyperlipidemia, chronic liver disease, stroke, and depression.

Osteoporosis risk was higher in patients with keloids compared to controls, especially in young subjects and subjects without comorbidities.

• Epidemiology
• Inflammation
• Keloid
• Osteoporosis
• Population-based study

• Black African
• DLQI
• Keloid
• QoL

• Burn
• Burn scar contracture
• Face
• Head
• Outcome
• Treatment

• collagen
• explant
• fibroblast
• keloid
• radiation
• radiotherapy
• recurrence
• steroid
• treatment schedule
• triamcinolone

• Fibroblast
• Hypertrophic scar
• Keloid
• Smad
• TGF-β
• Therapeutic strategies

• Scar
• Scar prevention
• Scar treatment
• Silicon gel
• Testosterone
• Top surgery
• Transmen

• Local steroid injection
• Scar contracture
• Transoral videolaryngoscopic surgery

• Keloids
• management
• recurrence
• scar
• treatment
• wound healing

• MSC
• biological strategies
• hypertrophic scar
• prevention
• wound healing

Keloid disorder (KD) is a fibroproliferative condition characterized by excessive dermal collagen deposition in response to wounding and/or inflammation of the skin. Despite intensive research, treatment for KD remains empirical and unsatisfactory. Activation of the renin-angiotensin system (RAS) leads to fibrosis in various organs through its direct effect and the resultant hypertension, and activation of the immune system. The observation of an increased incidence of KD in dark-skinned individuals who are predisposed to vitamin D deficiency (VDD) and hypertension, and the association of KD with hypertension and VDD, all of which are associated with an elevated activity of the RAS, provides clues to the pathogenesis of KD. There is increasing evidence implicating embryonic-like stem (ESC) cells that express ESC markers within keloid-associated lymphoid tissues (KALTs) in keloid lesions. These primitive cells express components of the RAS, cathepsins B, D, and G that constitute bypass loops of the RAS, and vitamin D receptor (VDR). This suggests that the RAS directly, and through signaling pathways that converge on the RAS, including VDR-mediated mechanisms and the immune system, may play a critical role in regulating the primitive population within the KALTs. This review discusses the role of the RAS, its relationship with hypertension, vitamin D, VDR, VDD, and the immune system that provide a microenvironmental niche in regulating the ESC-like cells within the KALTs. These ESC-like cells may be a novel therapeutic target for the treatment of this enigmatic and challenging condition, by modulating the RAS using inhibitors of the RAS and its bypass loops and convergent signaling pathways.

• cathepsins
• embryonic stem cells
• immune system
• keloid disorder
• keloid lesion
• keloid-associated lymphoid tissue
• renin-angiotensin system
• vitamin D deficiency