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1.
J Drugs Dermatol ; 23(7): 510-514, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954622

ABSTRACT

BACKGROUND: The prevalence of social media as a source of medical information has grown substantially in recent years, especially for skin conditions disproportionately affecting individuals with skin of color, such as melasma, keloids, and vitiligo. OBJECTIVE: This study aims to evaluate the nature of content related to these conditions on social media platforms, Instagram and TikTok. METHODS: In March 2023, the top five hashtags for melasma, keloid, and vitiligo were identified on both platforms. For each hashtag, the 10 most popular posts were selected, based on Instagram and TikTok algorithms. A content analysis was conducted, categorizing posts as Educational, Promotional, or Inspirational. Posts were further classified by content creator type. RESULTS: For the top 50 posts related to melasma on Instagram, the majority were promotional (58%), with the most common source being non-dermatologist social media influencers (50%). Dermatologists were the primary content creators for specific hashtags, such as #Melasma on TikTok, where the content was predominantly educational. CONCLUSION: Considering the high prevalence of dermatologist-creator content on TikTok, it is crucial to continue this shift toward dermatologist-driven educational content, as social media platforms continue to grow. These platforms are valuable channels for dermatologists to educate a broader audience, facilitating the dissemination of accurate medical information.J Drugs Dermatol. 2024;23(7):510-514. doi:10.36849/JDD.7716.


Subject(s)
Keloid , Melanosis , Skin Pigmentation , Social Media , Vitiligo , Social Media/statistics & numerical data , Humans , Vitiligo/therapy , Vitiligo/diagnosis , Vitiligo/psychology , Keloid/epidemiology , Melanosis/diagnosis , Dermatologists/statistics & numerical data
2.
BMJ Open ; 14(7): e084939, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38986560

ABSTRACT

INTRODUCTION: Keloids, benign fibroproliferative tumours characterised by excessive fibroblast proliferation and over-deposition of extracellular matrix, pose a therapeutic challenge with high recurrence rates. Betamethasone (diprospan) injection (BI) is one of the most common non-invasive therapies for keloids. Pulsed dye laser (PDL) has the function of closing microvessels, which may become one of the auxiliary treatment methods of BI and may enhance its curative effect. Some studies suggest that the combination of a dual-wavelength dye laser (DWL) and BI may offer superior efficacy. This randomised controlled trial aims to evaluate whether the combined therapy of DWL+BI outperforms BI alone in treating keloids. METHODS AND ANALYSIS: This single-centre, parallel positive control, randomised trial evaluates the efficacy and safety of DWL (585 nm PDL+1064 nm neodymium-doped yttrium aluminium garnet) combined with BI for keloid treatment. Enrolling 66 adult patients, participants are randomised into DWL+BI or BI groups in a 1:1 ratio. Over 12 weeks, each group undergoes four treatment sessions, ensuring blinding for outcome assessors. Data collection occurs at multiple time points (4, 12, 24 and 52 weeks), with primary outcomes assessing the Vancouver Scar Scale (VSS) improvement rate 24 weeks after the last intervention. Secondary outcomes include VSS improvement rates, changes in keloid volume, changes in relative perfusion index measured by laser speckle contrast imaging, Patient and Observer Scar Assessment Scale results and patient satisfaction. Safety assessments include vital signs, laboratory tests, pregnancy tests and self-reports of adverse reactions. ETHICS AND DISSEMINATION: The results will be presented in peer-reviewed journals and at international conferences. This study is approved by the Ethics Committee of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register (ChiCTR2400080148).


Subject(s)
Betamethasone , Keloid , Lasers, Dye , Humans , Keloid/therapy , Keloid/drug therapy , Betamethasone/administration & dosage , Betamethasone/therapeutic use , Lasers, Dye/therapeutic use , Adult , Female , Randomized Controlled Trials as Topic , Male , Combined Modality Therapy , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Treatment Outcome , Middle Aged , Young Adult , Adolescent
3.
Pathol Oncol Res ; 30: 1611789, 2024.
Article in English | MEDLINE | ID: mdl-38903488

ABSTRACT

Background: The desmoplastic reaction is considered a promising prognostic parameter for colorectal cancer. However, intermediate desmoplastic reaction is characterized by sizeable stromal heterogeneity, including both small amounts of keloid-like collagen (KC) in the fibrotic stroma and thick tufts of KC circumferentially surrounding cancer nests and occupying most of the fields of view. The present study aimed to evaluate the diagnostic and prognostic significance of KC histophenotyping with a quantitative visual assessment of its presence in the stroma of the invasive margin of TNM (The "tumor-node-metastasis" classification) stage II/III colorectal cancer (CRC). Methods and results: 175 resected tumors from patients with TNM stage II/III CRC were examined. Keloid-like collagen was assessed according to Ueno H. criteria. KC was assessed at the primary tumor invasive margin using Hematoxylin & Eosin and Masson's trichrome staining. The cut-off point for KC was examined using "the best cutoff approach by log-rank test." Using a cutoff point of 30%, we histologically divided fibrous stroma in the invasive area into two groups: "type A"-KC ≤ 0.3 and "type B"-KC>0.3. Type A stroma was observed in 48% of patients, type B-in 52%. The association between collagen amount and 5-year recurrence-free survival (5-RFS) was assessed using Cox regression analysis. Kaplan-Meier analysis and log-rank tests were used to assess the significance of survival analysis. Analysis of categorical variables showed that increased KC in CRC stroma predicted adverse outcomes for 5-RFS (hazard ratio [HR] = 3.143, 95%, confidence interval [CI] = 1.643-6.012, p = 0.001). Moreover, in Kaplan-Meier analysis, the log-rank test showed that type B exhibited worse 5-RFS than type A (p = 0.000). Conclusion: KC is an independent predictor of 5-year overall and RFS in patients with TNM stage II/III CRC treated with surgery, with worse survival rates when the amount of KC increases by >30%.


Subject(s)
Collagen , Colorectal Neoplasms , Extracellular Matrix , Keloid , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Male , Female , Prognosis , Middle Aged , Collagen/metabolism , Aged , Extracellular Matrix/pathology , Extracellular Matrix/metabolism , Keloid/pathology , Keloid/metabolism , Adult , Aged, 80 and over , Survival Rate , Follow-Up Studies
4.
Int J Mol Sci ; 25(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38892032

ABSTRACT

Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP), an inhibitor of the high-mobility group box 1 (HMGB1) and TGF-ß1 pathways, has emerged as a potential anti-fibrotic agent. Our research evaluated EP's effects on keloid fibroblast (KF) proliferation and ECM production, employing both in vitro cell cultures and ex vivo patient-derived keloid spheroids. We also analyzed the expression levels of ECM components in keloid tissue spheroids treated with EP through immunohistochemistry. Findings revealed that EP treatment impedes the nuclear translocation of HMGB1 and diminishes KF proliferation. Additionally, EP significantly lowered mRNA and protein levels of collagen I and III by attenuating TGF-ß1 and pSmad2/3 complex expression in both human dermal fibroblasts and KFs. Moreover, metalloproteinase I (MMP-1) and MMP-3 mRNA levels saw a notable increase following EP administration. In keloid spheroids, EP induced a dose-dependent reduction in ECM component expression. Immunohistochemical and western blot analyses confirmed significant declines in collagen I, collagen III, fibronectin, elastin, TGF-ß, AKT, and ERK 1/2 expression levels. These outcomes underscore EP's antifibrotic potential, suggesting its viability as a therapeutic approach for keloids.


Subject(s)
Fibroblasts , Keloid , Pyruvates , Spheroids, Cellular , Humans , Keloid/metabolism , Keloid/pathology , Fibroblasts/metabolism , Fibroblasts/drug effects , Pyruvates/pharmacology , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 1/genetics , Transforming Growth Factor beta1/metabolism , HMGB1 Protein/metabolism , HMGB1 Protein/genetics , Collagen/metabolism , Collagen/biosynthesis , Cell Proliferation/drug effects , Cells, Cultured , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinase 3/genetics , Extracellular Matrix/metabolism , Extracellular Matrix/drug effects , Collagen Type I/metabolism , Collagen Type I/genetics , Smad2 Protein/metabolism , Smad2 Protein/genetics , Smad3 Protein/metabolism , Up-Regulation/drug effects , Male
6.
Arch Dermatol Res ; 316(7): 412, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878082

ABSTRACT

Keloid scars and folliculitis keloidalis nuchae (FKN) are benign fibroproliferative dermal lesions of unknown aetiology and ill-defined treatment, which typically present in genetically susceptible individuals. Their pathognomonic hallmarks include local aggressive invasive behaviour plus high recurrence post-therapy. In view of this, we investigated proliferative and key parameters of bioenergetic cellular characteristics of site-specific keloid-derived fibroblasts (intra(centre)- and peri(margin)-lesional) and FKN compared to normal skin and normal flat non-hypertrophic scar fibroblasts as negative controls.The results showed statistically significant (P < 0.01) and variable growth dynamics with increased proliferation and migration in keloid fibroblasts, while FKN fibroblasts showed a significant (P < 0.001) increase in proliferation but similar migration profile to controls. A statistically significant metabolic switch towards aerobic glycolysis in the fibroblasts from the disease conditions was noted. Furthermore, an increase in basal glycolysis with a concomitant increase in the cellular maximum glycolytic capacity was also demonstrated in perilesional keloid and FKN fibroblasts (P < 0.05). Mitochondrial function parameters showed increased oxidative phosphorylation in the disease conditions (P < 0.05) indicating functional mitochondria. These findings further suggest that Keloids and FKN demonstrate a switch to a metabolic phenotype of aerobic glycolysis. Increased glycolytic flux inhibition is a potential mechanistic basis for future therapy.


Subject(s)
Cell Proliferation , Fibroblasts , Folliculitis , Glycolysis , Keloid , Humans , Keloid/metabolism , Keloid/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , Folliculitis/metabolism , Folliculitis/pathology , Mitochondria/metabolism , Mitochondria/pathology , Cells, Cultured , Oxidative Phosphorylation , Cell Movement , Adult , Skin/pathology , Skin/metabolism , Energy Metabolism , Female , Male
7.
Exp Dermatol ; 33(6): e15111, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840411

ABSTRACT

Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS-AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS-AS1 and miR-196a-5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS-AS1, miR-196a-5p and C-X-C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS-AS1 and CXCL12 expression were upregulated and miR-196a-5p expression was downregulated in clinical tissues from patients with keloids. GNAS-AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR-196a-5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS-AS1 transcription through GNAS-AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS-AS1 expression. GNAS-AS1 positively regulated CXCL12 by sponging miR-196-5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS-AS1/miR-196a-5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.


Subject(s)
Cell Proliferation , Chemokine CXCL12 , Fibroblasts , Keloid , MicroRNAs , RNA, Long Noncoding , STAT3 Transcription Factor , Keloid/metabolism , Keloid/genetics , Keloid/pathology , Humans , MicroRNAs/metabolism , MicroRNAs/genetics , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Chemokine CXCL12/metabolism , Chemokine CXCL12/genetics , Fibroblasts/metabolism , Cell Movement , Feedback, Physiological , Chromogranins/genetics , Chromogranins/metabolism , Male , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , GTP-Binding Protein alpha Subunits, Gs/metabolism , Signal Transduction , Adult , Cells, Cultured , Up-Regulation
8.
Arch Dermatol Res ; 316(7): 368, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850361

ABSTRACT

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.


Subject(s)
Keloid , Triamcinolone Acetonide , Keloid/drug therapy , Keloid/pathology , Humans , Triamcinolone Acetonide/pharmacokinetics , Triamcinolone Acetonide/administration & dosage , Adult , Female , Tissue Distribution , Male , Middle Aged , Injections, Intralesional , Skin/metabolism , Skin/pathology , Skin/diagnostic imaging , Cryoultramicrotomy/methods , Young Adult , Imaging, Three-Dimensional , Drug Delivery Systems/methods
9.
Toxicol Appl Pharmacol ; 489: 117012, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38906511

ABSTRACT

Keloid formation has been linked to abnormal fibroblast function, such as excessive proliferation and extracellular matrix (ECM) production. Serum deprivation protein response (SDPR) is a crucial regulator of cellular function under diverse pathological conditions, yet its role in keloid formation remains unknown. The current work investigated the function of SDPR in regulating the proliferation, motility, and ECM production of keloid fibroblasts (KFs), as well as to decipher the mechanisms involved. Analysis of RNA sequencing data from the GEO database demonstrated significant down-regulation of SDPR in KF compared to normal fibroblasts (NFs). This down-regulation was also observed in clinical keloid specimens and isolated KFs. Overexpression of SDPR suppressed the proliferation, motility, and ECM production of KFs, while depletion of SDPR exacerbated the enhancing impact of TGF-ß1 on the proliferation, motility, and ECM production of NFs. Mechanistic studies revealed that SDPR overexpression repressed TGF-ß/Smad signal cascade activation in KFs along with decreased levels of phosphorylated Samd2/3, while SDPR depletion exacerbated TGF-ß/Smad activation in TGF-ß1-stimulated NFs. SDPR overexpression also repressed ERK1/2 activation in KFs, while SDPR depletion exacerbated ERK1/2 activation in TGF-ß1-stimulated NFs. Inhibition of ERK1/2 abolished SDPR-depletion-induced TGF-ß1/Smad activation, cell proliferation, motility, and ECM production in NFs. In conclusion, SDPR represses the proliferation, motility, and ECM production in KFs by blocking the TGF-ß1/Smad pathway in an ERK1/2-dependent manner. The findings highlight the role of SDPR in regulating abnormal behaviors of fibroblasts associated with keloid formation and suggest it as a potential target for anti-keloid therapy development.


Subject(s)
Cell Movement , Cell Proliferation , Extracellular Matrix , Fibroblasts , Keloid , MAP Kinase Signaling System , Smad Proteins , Transforming Growth Factor beta1 , Humans , Keloid/pathology , Keloid/metabolism , Keloid/genetics , Fibroblasts/drug effects , Fibroblasts/metabolism , Cell Proliferation/drug effects , Cell Movement/drug effects , Transforming Growth Factor beta1/metabolism , Extracellular Matrix/metabolism , Extracellular Matrix/drug effects , Smad Proteins/metabolism , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Signal Transduction , Cells, Cultured , Mitogen-Activated Protein Kinase 1/metabolism , Male , Female , Mitogen-Activated Protein Kinase 3/metabolism , Adult
10.
Int Immunopharmacol ; 137: 112423, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38861914

ABSTRACT

Fibrosis is the excessive deposition of extracellular matrix in an organ or tissue that results from an impaired tissue repair in response to tissue injury or chronic inflammation. The progressive nature of fibrotic diseases and limited treatment options represent significant healthcare challenges. Despite the substantial progress in understanding the mechanisms of fibrosis, a gap persists translating this knowledge into effective therapeutics. Here, we discuss the critical mediators involved in fibrosis and the role of tranilast as a potential antifibrotic drug to treat fibrotic conditions. Tranilast, an antiallergy drug, is a derivative of tryptophan and has been studied for its role in various fibrotic diseases. These include scleroderma, keloid and hypertrophic scars, liver fibrosis, renal fibrosis, cardiac fibrosis, pulmonary fibrosis, and uterine fibroids. Tranilast exerts antifibrotic effects by suppressing fibrotic pathways, including TGF-ß, and MPAK. Because it disrupts fibrotic pathways and has demonstrated beneficial effects against keloid and hypertrophic scars, tranilast could be used to treat other conditions characterized by fibrosis.


Subject(s)
Fibrosis , Signal Transduction , ortho-Aminobenzoates , Humans , ortho-Aminobenzoates/therapeutic use , ortho-Aminobenzoates/pharmacology , Fibrosis/drug therapy , Signal Transduction/drug effects , Animals , Antifibrotic Agents/therapeutic use , Antifibrotic Agents/pharmacology , Keloid/drug therapy , Keloid/pathology , Keloid/metabolism , Transforming Growth Factor beta/metabolism
11.
J Cell Biochem ; 125(7): e30609, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38860429

ABSTRACT

Keloid is a typical fibrotic and inflammatory skin disease with unclear mechanisms and few therapeutic targets. In this study, we found that BMP1 was significantly increased in a collagen high-expressing subtype of fibroblast by reanalyzing a public single-cell RNA-sequence data set of keloid. The number of BMP1-positive fibroblast cells was increased in keloid fibrotic loci. Increased levels of BMP1 were further validated in the skin tissues and fibroblasts from keloid patients. Additionally, a positive correlation between BMP1 and the Keloid Area and Severity Index was found in keloid patients. In vitro analysis revealed collagen production, the phosphorylation levels of p65, and the IL-1ß secretion decreased in BMP1 interfered keloid fibroblasts. Besides, the knockdown of BMP1 inhibited the growth and migration of keloid fibroblast cells. Mechanistically, BMP1 inhibition downregulated the noncanonical TGF-ß pathways, including p-p38 and p-ERK1/2 signaling. Furthermore, we found the delivery of BMP1 siRNAs could significantly alleviate keloid in human keloid-bearing nude mice. Collectively, our results indicated that BMP1 exhibited various pathogenic effects on keloids as promoting cell proliferation, migration, inflammation, and ECM deposition of fibroblast cells by regulating the noncanonical TGF-ß/p38 MAPK, and TGF-ß/ERK pathways. BMP1-lowing strategies may appear as a potential new therapeutic target for keloid.


Subject(s)
Bone Morphogenetic Protein 1 , Fibroblasts , Inflammation , Keloid , Keloid/metabolism , Keloid/pathology , Keloid/genetics , Humans , Fibroblasts/metabolism , Fibroblasts/pathology , Bone Morphogenetic Protein 1/metabolism , Bone Morphogenetic Protein 1/genetics , Animals , Mice , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Male , Mice, Nude , Cell Proliferation , Female , Cell Movement , Fibrosis , Adult , Transforming Growth Factor beta/metabolism , MAP Kinase Signaling System
12.
PeerJ ; 12: e17551, 2024.
Article in English | MEDLINE | ID: mdl-38887622

ABSTRACT

Background: Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic disorders are significantly influenced by ferroptosis, and targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role and mechanism of ferroptosis in keloid development. Methods: Keloid tissues from keloid patients and normal skin tissues from healthy controls were collected. Iron content, lipid peroxidation (LPO) level, and the mRNA and protein expression of ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). Keloid fibroblasts (KFs) were isolated from keloid tissues, and treated with ferroptosis inhibitor ferrostatin-1 (fer-1) or ferroptosis activator erastin. Iron content, ferroptosis-related marker levels, LPO level, mitochondrial membrane potential, ATP content, and mitochondrial morphology in KFs were detected. Furthermore, the protein levels of α-smooth muscle actin (α-SMA), collagen I, and collagen III were measured to investigate whether ferroptosis affect fibrosis in KFs. Results: We found that iron content and LPO level were substantially elevated in keloid tissues and KFs. SLC7A11, GPX4, and Nrf2 were downregulated and TFRC was upregulated in keloid tissues and KFs. Mitochondria in keloid tissues and KFs exhibited ferroptosis-related pathology. Fer-1 treatment reduced iron content, restrained ferroptosis and mitochondrial dysfunction in KFs, Moreover, ferrostatin-1 restrained the protein expression of α-SMA, collagen I, and collagen III in KFs. Whereas erastin treatment showed the opposite results. Conclusion: Ferroptosis exists in keloid. Ferrostatin-1 restrained ECM deposition and fibrosis in keloid through inhibiting ferroptosis, and erastin induced ECM deposition and fibrosis through intensifying ferroptosis.


Subject(s)
Cyclohexylamines , Ferroptosis , Fibroblasts , Fibrosis , Keloid , NF-E2-Related Factor 2 , Phenylenediamines , Phospholipid Hydroperoxide Glutathione Peroxidase , Humans , Ferroptosis/drug effects , Keloid/pathology , Keloid/metabolism , Keloid/drug therapy , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Cyclohexylamines/pharmacology , Fibrosis/metabolism , Fibrosis/pathology , Phenylenediamines/pharmacology , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Male , Lipid Peroxidation/drug effects , Female , Adult , Iron/metabolism , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Receptors, Transferrin/metabolism , Receptors, Transferrin/genetics , Piperazines/pharmacology , Actins/metabolism , Actins/genetics , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Membrane Potential, Mitochondrial/drug effects
13.
Front Immunol ; 15: 1326728, 2024.
Article in English | MEDLINE | ID: mdl-38915394

ABSTRACT

Keloids are a common connective tissue disorder with an ill-understood etiopathogenesis and no effective treatment. This is exacerbated because of the absence of an animal model. Patient-derived primary keloid cells are insufficient as they age through passaging and have a limited supply. Therefore, there is an unmet need for development of a cellular model that can consistently and faithfully represent keloid's pathognomic features. In view of this, we developed keloid-derived immortalized fibroblast (KDIF) cell lines from primary keloid fibroblasts (PKF) by transfecting the human telomerase reverse transcriptase (hTERT) gene. The TERT gene encodes the catalytic subunit of the telomerase enzyme, which is responsible for maintaining the cellular replicative potential (cellular immortalization). Primary fibroblasts from keloid-specific lesional (peripheral, middle, and top) as well as extralesional sites were isolated and evaluated for cell line development and comparative cellular characteristics by employing qRT-PCR and immunofluorescence staining. Moreover, the immortalized behavior of KDIF cell lines was evaluated by comparing with cutaneous fibrosarcoma and dermatofibrosarcoma protuberans cell lines. Stable KDIF cell lines with elevated expression of hTERT exhibited the cellular characteristics of site-specific keloid fibroblasts. Histochemical staining for ß-galactosidase revealed a significantly lower number of ß-gal-positive cells in all three KDIF cell lines compared with that in PKFs. The cell growth curve pattern was studied over 10 passages for all three KDIF cell lines and was compared with the control groups. The results showed that all three KDIF cell lines grew significantly faster and obtained a fast growing characteristic as compared to primary keloid and normal fibroblasts. Phenotypic behavior in growth potential is an indication of hTERT-mediated immortalized transformation. Cell migration analysis revealed that the top and middle KDIF cell lines exhibited similar migration trend as site-specific PKFs. Notably, peripheral KDIF cell line showed significantly enhanced cell migration in comparison to the primary peripheral fibroblasts. All KDIF cell lines expressed Collagen I protein as a keloid-associated fibrotic marker. Functional testing with triamcinolone inhibited cell migration in KDIF. ATCC short tandem repeat profiling validated the KDIF as keloid representative cell line. In summary, we provide the first novel KDIF cell lines. These cell lines overcome the limitations related to primary cell passaging and tissue supply due to immortalized features and present an accessible and consistent experimental model for keloid research.


Subject(s)
Fibroblasts , Keloid , Telomerase , Humans , Keloid/pathology , Keloid/metabolism , Fibroblasts/metabolism , Telomerase/genetics , Telomerase/metabolism , Cell Line , Cell Line, Transformed , Male , Female , Adult , Middle Aged
14.
Ann Acad Med Singap ; 53(2): 113-116, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38920235

ABSTRACT

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.


Subject(s)
Keloid , Humans , Keloid/therapy , Cicatrix, Hypertrophic/therapy , Cicatrix, Hypertrophic/drug therapy , RNA/therapeutic use , Dermatology/methods , Skin Diseases/therapy , Skin Diseases/drug therapy , Genetic Therapy/methods
15.
Int J Mol Sci ; 25(10)2024 May 13.
Article in English | MEDLINE | ID: mdl-38791322

ABSTRACT

A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.


Subject(s)
Genetic Predisposition to Disease , Interleukin-6 , Keloid , Polymorphism, Single Nucleotide , Receptors, Interleukin-6 , Humans , Keloid/genetics , Keloid/pathology , Interleukin-6/genetics , Receptors, Interleukin-6/genetics , Male , Female , Adult , Poland , Middle Aged , Promoter Regions, Genetic , Case-Control Studies , Haplotypes , Alleles , Adolescent , Young Adult , Gene Frequency , Genotype , Infant, Newborn , Genetic Association Studies
16.
Biomater Sci ; 12(13): 3321-3334, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38812375

ABSTRACT

Keloid is a type of scar formed by the overexpression of extracellular matrix substances from fibroblasts following inflammation after trauma. The existing keloid treatment methods include drug injection, surgical intervention, light exposure, cryotherapy, etc. However, these methods have limitations such as recurrence, low treatment efficacy, and side effects. Consequently, studies are being conducted on the treatment of keloids from the perspective of inflammatory mechanisms. In this study, keloid models are created to understand inflammatory mechanisms and explore treatment methods to address them. While previous studies have used animal models with gene mutations, chemical treatments, and keloid tissue transplantation, there are limitations in fully reproducing the characteristics of keloids unique to humans, and ethical issues related to animal welfare pose additional challenges. Consequently, studies are underway to create in vitro artificial skin models to simulate keloid disease and apply them to the development of treatments for skin diseases. In particular, herein, scaffold technologies that implement three-dimensional (3D) full-thickness keloid models are introduced to enhance mechanical properties as well as biological properties of tissues, such as cell proliferation, differentiation, and cellular interactions. It is anticipated that applying these technologies to the production of artificial skin for keloid simulation could contribute to the development of inflammatory keloid treatment techniques in the future.


Subject(s)
Keloid , Skin, Artificial , Keloid/therapy , Humans , Animals , Models, Biological , Tissue Engineering , Tissue Scaffolds/chemistry , Skin/metabolism , Skin/pathology
17.
Ann Plast Surg ; 92(6): 635-641, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38747571

ABSTRACT

BACKGROUND: Keloid is a dermal fibroproliferative disease unique to humans. Due to the ambiguity in its pathophysiology and the frequent recurrence of keloid, there is no clear consensus on the treatment of keloid and there are many treatment methods defined. In order to benefit from the positive effects of fat grafting on pathological scars, we applied fat grafting to patients who underwent keloid enucleation. METHODS: Fifteen ear keloid patients included in the study. All patients underwent the same surgical procedure by the same surgeon. Routine follow-ups and examinations were performed to evaluate the results and in addition, the Patient and Observer Scar Assessment Scale (POSAS) survey was used. RESULTS: In the study, 15 patients were followed for a median (IQR) period of 21 (13-28) months. No recurrence was observed in any patient during follow-up, which occurred for a median of 21 (13-28) months. In the questionnaire filled out by the patients, the preoperative median value was found to be 48 (IQR: 12), whereas the postoperative median value was found to be 14 (IQR: 8). According to the patients, there was a statistically significant ( P < 0.05) positive improvement after surgery. CONCLUSIONS: Historically, surgical procedures were avoided because the surgical recurrence rate was very high, but today, recurrence rates are decreasing with combined treatments. These treatment combinations may require more than one intervention and require frequent clinical follow-ups. With our technique of fat grafting after enucleation, the treatment was completed with a single operation and no additional intervention was required.


Subject(s)
Adipose Tissue , Keloid , Humans , Keloid/surgery , Male , Female , Adipose Tissue/transplantation , Adult , Follow-Up Studies , Treatment Outcome , Young Adult , Middle Aged , Adolescent , Ear Diseases/surgery
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 197-206, 2024 Feb 28.
Article in English, Chinese | MEDLINE | ID: mdl-38755716

ABSTRACT

Scars are classified into 5 types: Superficial scars, hypertrophic scars, atrophic scars, depressed scars, and keloid. These types are primarily characterized by abnormal production of fibroblasts and collagen, as well as the disorderly arrangement of connective tissue. Laser treatment for scars involves the coordinated activation of various signaling pathways and cytokines. However, the exact pathological mechanism for scar formation remains unclear, leading to a lack of radical treatment. Recently, laser treatment has gained popularity as a new minimally invasive approach for scar treatment. The emergence of new theories such as fractional, picosecond laser, and laser-assisted drug delivery has led to continuous advance in laser treatment. Up to now, it has been developed numerous novel treatments, including combined with drug, physical, and other treatments, which have shown superior therapeutic effects. In order to optimize laser treatment in the future, it is crucial to combine new materials with postoperative care. This will help clinicians develop more comprehensive treatment strategies. Therefore, it is important to explore treatment options that have broader applicability.


Subject(s)
Cicatrix , Keloid , Laser Therapy , Humans , Cicatrix/therapy , Laser Therapy/methods , Keloid/radiotherapy , Keloid/therapy , Cicatrix, Hypertrophic/radiotherapy , Cicatrix, Hypertrophic/therapy
19.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731893

ABSTRACT

Keloids (KD) and hypertrophic scars (HTS), which are quite raised and pigmented and have increased vascularization and cellularity, are formed due to the impaired healing process of cutaneous injuries in some individuals having family history and genetic factors. These scars decrease the quality of life (QOL) of patients greatly, due to the pain, itching, contracture, cosmetic problems, and so on, depending on the location of the scars. Treatment/prevention that will satisfy patients' QOL is still under development. In this article, we review pharmacotherapy for treating KD and HTS, including the prevention of postsurgical recurrence (especially KD). Pharmacotherapy involves monotherapy using a single drug and combination pharmacotherapy using multiple drugs, where drugs are administered orally, topically and/or through intralesional injection. In addition, pharmacotherapy for KD/HTS is sometimes combined with surgical excision and/or with physical therapy such as cryotherapy, laser therapy, radiotherapy including brachytherapy, and silicone gel/sheeting. The results regarding the clinical effectiveness of each mono-pharmacotherapy for KD/HTS are not always consistent but rather scattered among researchers. Multimodal combination pharmacotherapy that targets multiple sites simultaneously is more effective than mono-pharmacotherapy. The literature was searched using PubMed, Google Scholar, and Online search engines.


Subject(s)
Cicatrix, Hypertrophic , Keloid , Humans , Keloid/drug therapy , Keloid/therapy , Cicatrix, Hypertrophic/drug therapy , Cicatrix, Hypertrophic/therapy , Combined Modality Therapy , Quality of Life
20.
Article in Chinese | MEDLINE | ID: mdl-38563174

ABSTRACT

Objective:To explore the clinical efficacy of surgical excision combined with low-energy X-ray irradiation in the treatment of ear keloids. Methods:Clinical data of 32 cases of ear keloid lesions that received surgical treatment alone or surgery combined with radiotherapy from March 2019 to November 2022 in the Department of Otorhinolaryngology Head and Neck Surgery of the Tianjin First Central Hospital were retrospectively analyzed. Among them, 10 cases received radiotherapy and 22 cases did not receive radiotherapy. The radiotherapy group received irradiation with a large divided dose of 50 kV low-energy X-rays. The mode of fractionation radiotherapy was as follows: the first was 10 Gy of intraoperative radiation therapy and the second was 8 Gy on the 3rd postoperative day for a total of 18 Gy. The local efficacy and skin radiation reaction were observed at a follow-up of 8-52 months. Results:The median follow-up was 26 months, and as of the date of the last follow-up, 9 cases were cured and 1 case was ineffective in the radiotherapy group, with an effective rate of 90.0%, while 9 cases were cured and 13 cases were ineffective in the no-radiotherapy group, with an effective rate of 40.9%. The recurrence of ear keloids was not related to the side, site, or etiology of the patient's onset(P>0.05). Recurrence was related to whether or not the patients received radiotherapy(χ²=4.885, P<0.05), and the recurrence rate in the radiotherapy group(10.0%) was significantly lower than that in the non-radiotherapy group(59.1%). Conclusion:Surgical excision combined with low-energy X-ray irradiation therapy is an effective method of treating keloids in the ear, especially with intraoperative radiation therapy can achieve more satisfactory results.


Subject(s)
Keloid , Humans , X-Rays , Keloid/radiotherapy , Keloid/surgery , Retrospective Studies , Treatment Outcome , Combined Modality Therapy , Recurrence
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