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1.
Cytokine ; 141: 155444, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33529888

RESUMO

BACKGROUND: Rosacea is a chronic inflammatory skin disease whose psychological consequences severely affect patient's quality of life. OBJECTIVE: To identify candidate genes of rosacea for potential development of new target therapies. METHODS: Gene Expression Omnibus datasets were retrieved to obtain differentially expressed genes (DEGs) between rosacea patients and healthy controls. Gene ontology (GO) analyses were used to identify functions of candidate genes. Related signaling pathways of DEGs were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis. Protein-protein interaction (PPI) networks were applied using search tools for the retrieval of interacting genes/proteins and modulations involving PPI networks were evaluated with use of the MCODE app. RESULTS: Samples from 19 rosacea patients and 10 healthy controls of dataset GSE65914 were enrolled. A total of 215 DEGs, 115 GO terms and 6 KEGG pathways were identified. A total of 182 nodes and 456 edges were enriched in PPI networks. Maximal clusters showed 15 central nodes and 96 edges. The toll-like receptor (TLR) signaling pathway was the most significant pathway detected and 5 DEGs were identified as candidate genes which included TLR2, C-C motif chemokine (CCL) 5, C-X-C motif chemokine ligand (CXCL) 9, CXCL10 and CXCL11. The results were verified in rosacea patients with use of real-time polymerase chain reaction and immunohistochemistry. Cell-type enrichment analysis revealed 8 lymphocytes that were enriched in rosacea patients. CONCLUSIONS: The results suggest that both innate and adaptive immune responses were involved in the etiology of rosacea. Five DEGs in the TLR signaling pathway may serve as potential therapeutic target genes.

2.
Lasers Med Sci ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389306

RESUMO

This study is to determine the role of the fractional CO2 laser in topical drug delivery and the impact of local immune responses. Experimental rabbit nails were treated with fractionated CO2 laser at varied fluencies of 20 mJ, 25 mJ, and 30 mJ and half of which were coated with rhodamine B (RhB). Histological examination was performed by hematoxylin and eosin staining; the penetration of RhB was assessed by the use of confocal laser scanning microscopy; and the expressions of IFN-γ and IL-4 mRNA in situ were detected by means of qPCR at 12 h, 24 h, 3 days, and 7 days post-laser irritation. The fractional CO2 laser could generate microscopic treatment zones in nail plates, and the depths of these micropores as well as the permeation of RhB in nails increased significantly in an energy-dependent manner. Importantly, the laser irritation led an upregulation of local IFN-γ mRNA expression accompanied by a downregulation of IL-4 mRNA expression. The ultrapulsed ablative fractionated CO2 laser may assist topical drug delivery, and may drive stronger local Th1 responses due to an imbalance of IFN-γ/IL-4 expressions, suggesting that the combination of ablative fractionated CO2 laser with topical agents would be an effective option for the treatment of onychomycosis.

3.
J Cosmet Dermatol ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33356001

RESUMO

BACKGROUND: There is an increasing demand for fat reduction and body contouring procedures. Noninvasive radiofrequency devices have been used to tighten skin and treat cellulite, but there are few studies confirming their efficacy for abdominal fat reduction. OBJECTIVE: This study explored the effects of four noninvasive radiofrequency (RF) treatments on abdominal fat in Asian subjects, evaluating body weight, body mass index (BMI), and waist circumference. METHODS: In this study, 16 patients with abdominal obesity were treated four times with a noninvasive and contactless selective RF device (VANQUISH ME™, BTL Aesthetics). Treatments were 7 days apart and lasted 45 min each. The BMI and circumference of the upper, middle, and lower abdomen were measured at baseline and after each treatment. RESULTS: There were statistically significant reductions in BMI and abdominal circumference in all 16 patients (P < .05). Most patients only experienced a slight abdominal heat sensation and minimal body sweating during the treatment, and no adverse reactions were observed after the treatment. CONCLUSION: The noninvasive and contactless selective RF technique was effective and safe in reducing fat, BMI, and abdominal circumference.

4.
Dermatol Ther ; : e14572, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219732

RESUMO

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is an extremely rare subtype of primary cutaneous T cell lymphomas mimicking panniculitis. Clinically, patients are usually presented with subcutaneous nodules, which usually leads to initial misdiagnosis as a benign cutaneous condition. Here, we report a 40-year-old female who presented with subcutaneous erythematous nodules on her extremities with fever. On the basis of the clinical presentations, histopathological features and immunohistochemical findings, a diagnosis of SPTCL was made. The patient was treated with the injection of recombinant human interferon α-1b (30 µg) every other day for 3 months. The lesions gradually regressed. No new erythema nodules reappeared during the 10-month follow-up.

7.
Cell Prolif ; 53(11): e12916, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33058377

RESUMO

Healing after mammalian skin injury involves the interaction between numerous cellular constituents and regulatory factors, which together form three overlapping phases: an inflammatory response, a proliferation phase and a remodelling phase. Any slight variation in these three stages can substantially alter the healing process and resultant production of scars. Of particular significance are the mechanisms responsible for the scar-free phenomenon observed in the foetus. Uncovering such mechanisms would offer great expectations in the treatment of scars and therefore represents an important area of investigation. In this review, we provide a comprehensive summary of studies on injury-induced skin regeneration within the foetus. The information contained in these studies provides an opportunity for new insights into the treatment of clinical scars based on the cellular and molecular processes involved.


Assuntos
Cicatriz/fisiopatologia , Pele/fisiopatologia , Cicatrização , Adulto , Animais , Cicatriz/patologia , Feto/patologia , Feto/fisiopatologia , Fibroblastos/patologia , Humanos , Queratinócitos/patologia , Lesões Pré-Natais/patologia , Lesões Pré-Natais/fisiopatologia , Pele/embriologia , Pele/lesões , Pele/patologia
8.
Chin Med J (Engl) ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925288

RESUMO

BACKGROUND: Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia. METHODS: Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein. RESULTS: DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ±â€Š989.10 vs. 4272.67 ±â€Š918.50, P < 0.05). In response to hyperthermia, F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia (WT cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.34 ±â€Š0.02 vs. 0.24 ±â€Š0.01, 0.31 ±â€Š0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ±â€Š0.01 vs. 0.30 ±â€Š0.01, 0.51 ±â€Š0.02, P < 0.001, P < 0.01). WT cells restored to baseline levels observed in the unheated condition, while DnaJA4-KO cells exceeded baseline levels in the recovery. As the upstream factors of F-actin, a similar profile in rho-associated serine/threonine kinase 1 (ROCK 1) and RhoA expressions was observed after hyperthermia. While E-cadherin expression was decreased in response to hyperthermia, it was increased in DnaJA4-KO cells compared with WT cells. CONCLUSIONS: Hyperthermia affects the expression levels of F-actin in HaCaT cells. DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia. DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.

9.
J Cosmet Dermatol ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32783330

RESUMO

BACKGROUND: Infraorbital dark circles (DC) are defined as a symptom that presents darkness under infraorbital eyelids. The objective of this study was to evaluate the efficacy and safety of nano-microneedle-assisted phenylethyl resorcinol (PR) for the treatment of infraorbital dark circles. METHODS: Twenty female participants were randomized to two groups. In the experimental group (group E), participants received topical PR gel under the left orbit once a day and topical plus nano-microneedle-assisted PR gel under the right orbit twice a week. In the control group (group C), participants were treated with gel without PR. Melanin index (MI) and erythema index (EI) were measured before the session (T0), 4 and 8 weeks during the treatment session (T4, T8), and 1 and 2 months after the last session (T12, T16). The global assessment was performed by a blinded dermatologist. RESULTS: The mean value of MI in group E was significantly lower than the baseline at T8 (P < .05), and the right side decreased more significantly than the left side (P < .05). However, there was no difference of MI before and after treatment in group C (P > .05). There was no big difference of the mean EI between the two sides (P > .05). The treatment was well tolerated, and no serious adverse effects were reported. CONCLUSION: PR combined with nano-microneedle could be an effective and safe method for infraorbital DC.

10.
J Cell Mol Med ; 24(17): 10027-10041, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32790210

RESUMO

Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point-dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up-regulation of miR-27a-5p and the latter could down-regulate SMAD2, and these results were verified by qRT-PCR or Western blot. Furthermore, UVA radiation (5 J/cm2 ), knocking down SIRT1 or overexpression of miR-27a-5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR-27a-5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR-27a-5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA-induced skin damage.

11.
Virol J ; 17(1): 99, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646520

RESUMO

BACKGROUND: Human papillomaviruses (HPVs), a group of non-enveloped small viruses with double-stranded circular DNA which lead to multiple skin diseases such as benign warts, are commonly seen in clinics. The current HPV detection systems aim mainly at mucosal HPVs, however, an efficient clinical approach for cutaneous HPVs detection is lacking. OBJECTIVES: To establish a rapid detection system for cutaneous HPVs using a colorimetric loop-mediated isothermal amplification (LAMP) with hydroxynaphthol blue (HNB) dye in combination with microfluidic technology. METHODS: L1 DNA sequences of the 30 cutaneous HPVs were chemically synthesized, and LAMP primers against L1 DNA were designed with use of an online LAMP designing tool. Isothermal amplification was performed with use of a water bath and the amplification results were inspected with the naked eye. Using PCR sequencing as a control method, the specificity and sensitivity of the new detection system were obtained by detecting clinical samples. RESULTS: The lower detection limit of the LAMP assay was 107 viral DNA copies/µl when tested on synthesized L1 DNA sequences, which was better than the conventional PCR. Compared to PCR sequencing, the sensitivity of HPV27, HPV2, HPV1, HPV57, HPV3, HPV4, HPV7 and HPV75 genotypes detections were 100%, whereas the specificity was 34.55, 45.12, 95.83, 98.59 and 97.62% respectively, when tested on clinical samples. CONCLUSIONS: The new cutaneous type HPV detection system is characterized by both a good sensitivity and specificity compared to conventional methods.

12.
Int J Mol Med ; 46(2): 880-888, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32626950

RESUMO

Interleukin (IL)­18, a pro­inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL­18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild­type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903­treated WT mice; and iv) MC903­treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD­like symptoms and severity were evaluated by the scoring of AD (SCORAD). Serum immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP) levels were determined with the use of an enzyme­linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL­1ß, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT­qPCR was performed to assess the mRNA levels of IL­1ß, IL­4, IL­9, STAT3, corticotropin­releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase­1 in the skin lesions. It was demonstrated that IL­18 may function as a pleiotropic pro­inflammatory cytokine in the development of AD­like lesions. IL­18 KO reduced aggravated AD­like lesions induced by MC903, in part by upregulating Th2 cytokines. IL­18 promoted the expression of FLG in the epidermis and CRHR2 in AD­like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL­18 deficiency alleviates AD­induced lesions in mice.

13.
Front Pharmacol ; 11: 736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32499710

RESUMO

Photodamages caused by UVA radiation induced oxidative injuries are closely related to photoaging and skin cancer. Paeoniflorin (PF), extracted from the root of Paeonia lactiflora, has been reported to be an effective antioxidant. PLIN2, known as adipose differentiation-related protein, has been previously involved in the regulation of oxidative stress. In this study, we were sought to investigate the photo-protective property of PF and PLIN2 in UVA-radiated human dermal fibroblasts (HDFs). HDFs were pre-treated with PF (800 µM) followed by UVA radiation (22.5 J/cm2). MTS activity, cell apoptosis, ROS, MDA, and SOD were detected, respectively. The expressions of Nrf2, HO-1, NQ-O1, and PLIN2 were determined using RT-qPCR or western blot. Nrf2 was silenced by siRNA, and PLIN2 was overexpressed via lentiviral transduction. Comparing to the UVA radiation, PF pre-treatment could prominently increase the MTS activity, decrease cell apoptosis, reduce the generations of ROS and MDA, increase the activity of SOD and increase the expression of Nrf2 and its target genes HO-1 and NQ-O1. When Nrf2 was knocked down, PF lost above protective properties. In addition, UVA induced oxidative stress led to upregulation of PLIN2 and the latter could be decreased by PF. Overexpression of PLIN2 improved MTS activity and reduced MDA level in HDFs. The combination of PLIN2 overexpression and PF pre-treatment corporately inhibited UVA-induced injury. Besides, we also found that PF and PLIN2 had a compensatory protection against UVA induced oxidative stress. In conclusion, our study demonstrated that UVA induced photodamages could be inhibited by PF via Nrf2/HO-1/NQ-O1 signaling pathway or by PLIN2, and the combination of PLIN2 overexpression and PF played additive effects against UVA-related oxidative stress.

14.
Front Pharmacol ; 11: 536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410998

RESUMO

Paeoniflorin (PF) possesses multiple biological functions including anti-oxidization. PF is the major bioactive ingredient of total glycosides of paeony (TGP), which could promote re-pigmentation of vitiligo. The study was sought to investigate the effects and potential signaling pathways of PF on hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes. The results showed that pretreatment with 50 µM PF significantly inhibited cell apoptosis, enhanced cell viability, and suppressed reactive oxygen species (ROS) accumulation by enhancing the productions of superoxide dismutase (SOD) and antioxidant enzymes catalase (CAT). Furthermore, PF activated c-Jun amino terminal kinase (JNK) and the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway to counteract H2O2-induced oxidative damage in PIG1 and PIG3V. Taken together, our study firstly demonstrates that PF resists H2O2-induced oxidative stress in melanocytes probably by activating JNK/Nrf2/HO-1 signaling, suggesting a potential therapeutic application of PF on vitiligo.

15.
Food Funct ; 11(6): 5105-5114, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32356551

RESUMO

Phytochemicals from functional foods are common ingredients in dietary supplements and cosmetic products for anti-skin aging effects due to their antioxidant activities. A proprietary red maple (Acer rubrum) leaf extract (Maplifa™) and its major phenolic compound, ginnalin A (GA), have been reported to show antioxidant, anti-melanogenesis, and anti-glycation effects but their protective effects against oxidative stress in human skin cells remain unknown. Herein, we investigated the cytoprotective effects of Maplifa™ and GA against hydrogen peroxide (H2O2) and methylglyoxal (MGO)-induced oxidative stress in human keratinocytes (HaCaT cells). H2O2 and MGO (both at 400 µM) induced toxicity in HaCaT cells and reduced their viability to 59.2 and 61.6%, respectively. Treatment of Maplifa™ (50 µg mL-1) and GA (50 µM) increased the viability of H2O2- and MGO-treated cells by 22.0 and 15.5%, respectively. Maplifa™ and GA also showed cytoprotective effects by reducing H2O2-induced apoptosis in HaCaT cells by 8.0 and 7.2%, respectively. The anti-apoptotic effect of Maplifa™ was further supported by the decreased levels of apoptosis associated enzymes including caspases-3/7 and -8 in HaCaT cells by 49.5 and 19.0%, respectively. In addition, Maplifa™ (50 µg mL-1) and GA (50 µM) reduced H2O2- and MGO-induced reactive oxygen species (ROS) by 84.1 and 56.8%, respectively. Furthermore, flow cytometry analysis showed that Maplifa™ and GA reduced MGO-induced total cellular ROS production while increasing mitochondria-derived ROS production in HaCaT cells. The cytoprotective effects of Maplifa™ and GA in human keratinocytes support their potential utilization for cosmetic and/or dermatological applications.

16.
Cell Res ; 30(10): 854-872, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32457396

RESUMO

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

17.
Dermatol Ther ; 33(3): e13426, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32301192

RESUMO

Reactive carbonyl species including methylglyoxal (MGO) are oxidation metabolites of glucose and precursors of advanced glycation end products (AGEs). They are important mediators of cellular oxidative stress and exacerbate skin complications. Published data supports that certain phenolic compounds can exert cellular protective effects by their antioxidant activity. A phenolic-enriched maple syrup extract (MSX) was previously reported to show protective effects against AGEs- and MGO-induced cytotoxicity in human colon cells but its skin protective effects remain unknown. The protective effects of MSX were evaluated against hydrogen peroxide (H2 O2 )- and MGO-induced cytotoxicity in human keratinocytes (HaCaT cells). Cellular viability and antioxidant activity were evaluated by the luminescent cell viability CellTiter-Glo assay and the reactive oxygen species (ROS) assay, respectively. A single-cell gel electrophoresis (Comet assay) was used to measure the strand breaks in the DNA of HaCaT cells. MSX (at 50 µg/mL) ameliorated H2 O2 - and MGO-induced cytotoxicity by increasing cell viability by 21.5% and 25.9%, respectively. MSX reduced H2 O2 - and MGO-induced ROS production by 69.4% and 56.6%, respectively. MSX also reduced MGO-induced DNA damage by 47.5%. MSX showed protective effects against H2 O2 - and MGO-induced cytotoxicity in HaCaT cells supporting its potential for dermatological and/or cosmeceutical applications.

18.
Int Wound J ; 17(2): 285-299, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31724831

RESUMO

Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria-infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low-moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2 . Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound-cytokine levels, wound-healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria-infected wound healing in animals by promoting wound closure and killing bacteria.

19.
Onco Targets Ther ; 12: 9395-9405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807020

RESUMO

Purpose: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has attracted extensive attention in various types of malignant tumors. However, the role of DNA-PKcs in cutaneous squamous cell carcinoma (cSCC) development has not been elucidated. In this study, we investigated the role of DNA-PKcs in cSCC and the molecular mechanisms of TGF-ß1-induced cSCC progression mediated by DNA-PKcs. Methods: We performed bioinformatic analysis and RT-PCR to examine the DNA-PKcs expression level in cSCC. Then, we downregulated DNA-PKcs using a DNA-PK-specific inhibitor or small interfering RNA (siRNA) to explore the effects of DNA-PKcs on SCL-1 cell migration and invasion. To further investigate the mechanism by which DNA-PKcs promotes cSCC progression, TGF-ß1 and the TGF-ß receptor (TGF-ßR) I/II dual inhibitor LY2109761 were used to examine whether DNA-PKcs participates in TGF-ß1/Smad signaling. Results: DNA-PKcs expression was upregulated in cSCC. DNA-PK inhibition or expression knockdown resulted in inhibited migration and invasion and altered epithelial-mesenchymal transition (EMT) marker expression patterns in SCL-1 cells. Importantly, TGF-ß1 mediated EMT induction in cSCC cells, and DNA-PKcs was identified as a TGF-ß1-responsive gene. TGF-ß1 promoted DNA-PKcs transcription, and DNA-PKcs enhanced the TGF-ß1-induced EMT program involved in cSCC invasion and metastasis by phosphorylating Smad3. Conclusion: This study is the first to show that DNA-PKcs mediates EMT to promote cSCC aggressiveness by targeting the TGF-ß1/Smad signaling pathway, which provides insight into how DNA-PKcs impacts cSCC progression and identifies a new therapeutic target.

20.
J Dermatolog Treat ; : 1-4, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31689168

RESUMO

Background: The application of fractional Q-switched ruby laser (FQSRL) or intense pulsed light (IPL) on Café-au-lait macule (CALM) is rational and the data are lacking.Objective: To evaluate the efficacy and safety of FQSRL and IPL in CALM.Methods: The patients with CALM who were treated with FQSRL or IPL were retrospectively observed from April 2016 to April 2019. The laser/light treatments were conducted at an interval of 3-4 weeks.Results: For FQSRL (N = 67), 88.23%, 95.46%, 100% patients achieved >50% improvement by three sessions, four sessions, and more than four sessions of treatment, respectively. A better and better efficacy was shown with the increasing number of sessions (χ2 = 89.51, p < .01). For IPL (N = 54), 45% and 87.5% achieved >50% improvement by three sessions and more than four sessions of treatments, respectively. More than four sessions achieved better efficacy than less sessions (p < .01). Under various time-points, FQSRL presented more favorable responses than IPL (p < .05). All the adverse effects were tolerable and acceptable.Conclusions: FQSRL or IPL would be an alternative and safe modality for CAML in Chinese patients.

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