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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (H2O2)‐ 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 H2O2‐ and MGO‐induced cytotoxicity by increasing cell viability by 21.5% and 25.9%, respectively. MSX reduced H2O2‐ 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 H2O2‐ and MGO‐induced cytotoxicity in HaCaT cells supporting its potential for dermatological and/or cosmeceutical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Striae gravidarum is a common skin condition resulting after pregnancy, caused by fibroblast dysfunction. Although not considered a disease, it may be considered cosmetically unpleasant to sufferers and remains as a therapeutic challenge to date. OBJECTIVE : To evaluate the efficacy and safety of a sublative bipolar fractional radiofrequency (FRF) system, associated with 0.1% topical tretinoin, in treating striae gravidarum. MATERIALS AND METHODS : Eighteen Chinese women with striae gravidarum on the abdomen were enrolled in the study. The target area of each patient was divided into 4 sites randomly: control, tretinoin, FRF, and tretinoin and FRF. Fractional RF was used 3 times, with 3-month intervals. Changes to striae gravidarum were evaluated through subjective scaling and objective measures, using both high-frequency ultrasound and histological study. RESULTS : Both subjective assessment and skin thickness differences demonstrated significant improvement in the combination site (p <.001). Average optical density and density percentage of neocollagen and elastic fibers were also markedly increased in the combination site (p <.05). The adverse effects of FRF were limited to mild pain and transient erythema, edema, and microcrusts. CONCLUSION: The combined therapy of FRF and topical tretinoin may be a potential method in treating striae gravidarum, with satisfactory efficacy and limited side effects. [ABSTRACT FROM AUTHOR]

Candida albicans is a commensal fungus that associates with human hosts. Under normal circumstances this interaction does not produce any severe life-threatening disease, as macrophages of the innate immune system will result in its clearance. However, disorders may arise in immunosuppressed individuals. To understand the bioactivity of Candida albicans cell wall polysaccharides, which represent an important component of its function, mannoprotein from this fungus was extracted, purified and analyzed. Mannoprotein with α-(1,2) and α-(1,6) linkages was investigated with use of HPLC and NMR. Co-incubation of mannoprotein with macrophages resulted in a mannoprotein with the potential to polarize macrophages to M1 and promote phagocytosis/microbial killing ability thus increasing the clearance of pathogens through Akt2. Moreover, mannoprotein within the cell wall promoted cell proliferation and inhibited apoptosis by activation of the Akt signaling pathway. Collectively, α-(1,6)(1,2)-mannoprotein, one of the five polysaccharides extracted from the cell wall of Candida albicans , demonstrates immune-enhancing effects by activation of the Akt signaling pathway. These findings provide important new insights into the biological effects of polysaccharides on macrophages. Such information can then serve as the foundation for the development of novel anti-fungal medications. • The polysaccharides of cell wall of Candida albicans were purified and identified. • α-(1,6)(1,2)-Mannoprotein polarized macrophage to M1 by activating Akt2. • α-(1,6)(1,2)-Mannoprotein accelerated cell cycle and inhibited apoptosis. • α-(1,6)(1,2)-Mannoprotein promoted phagocytosis and production of NO and ROS. [ABSTRACT FROM AUTHOR]

Flat warts (FWs) usually result from human papillomavirus (HPV) types 3, 10, 28 or 41. Induction therapy was conducted on days 1, 2, 3, 11 and 12, followed by five consecutive weekly sections of maintenance therapy. Treatment of high risk human papillomavirus infection in low grade cervical squamous intraepithelial lesion with mild local thermotherapy: three case reports. [Extracted from the article]

Background: Extramammary Paget's disease (EMPD), a rare skin malignancy with non-specific manifestations, is often misdiagnosed as eczema of scrotum or tinea cruris. Although the diagnosis of EMPD could be confirmed by biopsy, it can be delayed as patients are reluctant to receive invasive operations. Herein, we investigated the serum miRNA expressions of EMPD patients and compared to that of the eczema of scrotum or tinea cruris patients as well as health volunteers for potential diagnostic markers for EMPD.Methods: Altogether 45 subjects including 16 patients diagnosed with EMPD, 12 patients diagnosed with eczema of scrotum or tinea cruris and 17 healthy volunteers were enrolled in this study. Serum from all of subjects were collected to identify miRNAs (by miRNA array global normalization, RT-PCR validation, and receiver operating characteristic curve analysis) that could be potential diagnostic markers for EMPD.Results: The miRNA array analyses revealed that the expressions of 37 miRNAs from the EMPD patients were different (change ≥4-fold) from health volunteers. Among these miRNAs, the expression of miR-155 was significantly increased (p < 0.01) in the EMPD patients as compared with that of the health volunteers and the eczema of scrotum or the tinea cruris patients (no difference between these two control groups). In addition, receiver operating characteristic (ROC) curve analysis showed that diagnostic capacities (defined as the area under curve of ROC) of miR-155 are 0.85 (as compared with health volunteers group) and 0.81 (as compared with the eczema of scrotum or the tinea cruris patients group), respectively.Conclusion: The serum miRNA expression of gene miR-155 in the EMPD patients was differentiated from that of other subjects warranting further validation of miR-155 as a diagnostic marker of EMPD. [ABSTRACT FROM AUTHOR]

Highlights • Hyperthermia induces DNAJA4 expression and P65 phosphorylation in keratinocytes in the presence or absence of HPV infection. • DNAJA4-deficency promotes NF-kappa B (P65) pathway activation in HaCaT cells upon hyperthermia stimulation. • Hyperthermia combined with DNAJA4-deficency causes reduced viability of HaCaT cells. Abstract Background Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. Objectives To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. Methods HaCaT cells were subjected to 44 °C (compared to 37 °C) waterbath for 30 min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. Results DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB, 3 3 NF-kB: nuclear factor-kappa B. was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α 4 4 TNF-α: tumor necrosis factor-alpha. ; IL-1B, 5 5 IL-1B: interleukin-1 beta. TNFAIP3 6 6 TNFAIP3: Tumor necrosis factor alpha-induced protein 3. and IL-8 7 7 IL-8: interleukin-8. were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. Conclusions Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections. [ABSTRACT FROM AUTHOR]

Candida albicans ( C. albicans ) is a commensal organism in human and a well-known dimorphic opportunistic pathogenic fungus. Though plenty of researches on the pathogenesis of C. albicans have been performed, the mechanism is not fully understood. The cell wall components of C. albicans have been documented to play important roles in its pathogenic processes. To further study the infectious mechanism of C. albicans , we investigated the potential functional role of its cell wall mannoprotein in cell cycle and apoptosis of HaCaT cells. We found that mannoprotein could promote the transition of cell cycle from G1/G0 to S phase, in which Cyclin D1, CDK4 and p-Rb, the major regulators of the cell cycle progression, showed significant upregulation, and CDKN1A (cyclin dependent kinase inhibitor 1A (p21)) showed significant downregulation. Mannoprotein also could inhibit apoptosis of HaCaT cells, which was well associated with increased expression of BCL2 (Bcl-2). Moreover, mannoprotein could increase the phosphorylation levels of RELA (p65) and NFKBIA (IκBα), as the key factors of NF-κB signal pathway in HaCaT cells, suggesting the activation of NF-κB signal pathway. Additionally, a NF-κB specific inhibitor, PDTC, could rescue the effect of mannoprotein on cell cycle and apoptosis of HaCaT cells, which suggested that mannoprotein could activate NF-κB signal pathway to mediate cell cycle alternation and inhibit apoptosis. [ABSTRACT FROM AUTHOR]

Resistant non-segmental vitiligo is difficult to be treated. Ablative erbium-YAG (Er:YAG) laser has been used in the treatment of vitiligo, but the ablation of entire epidermis frustrated the compliance of patients. The purpose of this study is to investigate the effects of fractional Er:YAG laser followed by topical betamethasone and narrow band ultraviolet B (NB-UVB) therapy in the treatment of resistant non-segmental vitiligo. The vitiligo lesions of each enrolled patient were divided into four treatment parts, which were all irradiated with NB-UVB. Three parts were, respectively, treated with low, medium, or high energy of Er:YAG laser, followed by topical betamethasone solution application. A control part was spared with laser treatment and topical betamethasone. The treatment period lasted 6 months. The efficacy was assessed by two blinded dermatologists. Treatment protocol with high energy of 1800 mJ/P of fractional Er:YAG laser followed by topical betamethasone solution and in combination with NB-UVB made 60% patients achieve marked to excellent improvement in white patches. The protocol with medium energy of 1200 mJ/P of laser assisted approximate 36% patients achieve such improvement. The two protocols, respectively, showed better efficacies than NB-UVB only protocol. However, fractional Er:YAG laser at low energy of 600 mJ/P did not provide such contributions to the treatment of vitiligo. The fractional Er:YAG laser in combination with topical betamethasone solution and NB-UVB was suitable for resistant non-segmental vitiligo. The energy of laser was preferred to be set at relatively high level. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the efficacy and safety of using a 694-nm fractional Q-switched ruby laser to treat infraorbital dark circles. Thirty women with infraorbital dark circles (predominant color: dark/brown) participated in this open-labeled study. The participants received eight sessions of 694-nm fractional Q-switched ruby laser treatment using a fluence of 3.0-3.5 J/cm2, at an interval of 7 days. The melanin deposition in the lesional skin was observed in vivo using reflectance confocal microscopy (RCM). The morphological changes were evaluated using a global evaluation, an overall self-assessment, and a Mexameter. Twenty-eight of the 30 patients showed global improvements that they rated as excellent or good. Twenty-six patients rated their overall satisfaction as excellent or good. The melanin index indicated a substantial decrease from 240.44 (baseline) to 194.56 (P < 0.05). The RCM results showed a dramatic decrease in melanin deposition in the upper dermis. The adverse effects were minimal. The characteristic finding of dark/brown infraorbital dark circles is caused by increased melanin deposition in the upper dermis. The treatment of these infraorbital dark circles using a 694-nm fractional QSR laser is safe and effective. [ABSTRACT FROM AUTHOR]

There is a lack of data on treatment and prognosis of pemphigus in China. The aim of this study was to evaluate long-term follow-up and prognosis of pemphigus. Forty-seven inpatients with pemphigus vulgaris (PV) and 22 with pemphigus foliaceus (PF) were recruited in this retrospective study. The average age at onset was 51.6 and 54.9 years in PV and PF, respectively. Highdose systemic steroids were administered in 47 PV and 21 PF, of which 18 PV and 8 PF with adjuvant therapies. CD4 lymphocytopenia was found in 5 PV and 2 PF patients at admission and successfully treated by intravenous thymopentin daily. During a mean follow-up of 37.1 months, 41 PV and 19 PF reached remission, 30 PV and 9 PF relapsed, 4 PV and 2 PF died. Major causes of death were relapse of pemphigus due to discontinuation of oral steroids by the patients themselves (four cases) and severe infections (two cases, one with severe CD4 lymphocytopenia). The 1-year mortality rate of PV and PF was 8.5% and 4.5%, respectively. Cox regression analysis indicated that age at onset of pemphigus was an independent risk factor related to the elevated mortality. Our report confirmed the high mortality rate of pemphigus in a Chinese population and stressed that patient education was urgently needed to prevent relapses and deaths. [ABSTRACT FROM AUTHOR]

To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, Pcombined=8.07 × 10−12, odds ratio (OR)=1.18), 11q23.3 (rs638893, Pcombined=2.47 × 10−9, OR=1.22), and 10q22.1 (rs1417210, Pcombined=1.83 × 10−8, OR=0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, Pcombined=8.57 × 10−8, OR=0.88), 10p15.1 (rs3134883, Pcombined=1.01 × 10−5, OR=1.11), and 22q12.3 (rs2051582, Pcombined=2.12 × 10−5, OR=1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations. [ABSTRACT FROM AUTHOR]

Abstract: Recessive congenital methemoglobinemia (RCM) is a very rare disorder caused by NADH-cytochrome b5 reductase (cb5r) deficiency. Two distinct clinical forms, types I and II, caused by cb5r deficiency have been recognized. In type I, the enzyme deficiency is restricted only to erythrocytes with cyanosis being the only major symptom. In contrast, in type II, the enzyme deficiency is generalized to all tissues and associated with neurological impairment, mental and growth retardation and reduced life expectancy, in addition to cyanosis. Recently, we conducted a study on an 11-year-old boy with cb5r deficiency type I. The mutational analysis of the CYB5R3 gene revealed that the boy is homozygous for L72P mutation. Surprisingly, his mother is heterozygous for this L72P mutant, but not his father. Thirteen microsatellite markers of chromosome 22 were selected to analyze the origins of the patient''s chromosome 22. The result showed that both of the chromosome 22(s) of this patient came from the maternal side (uniparental heterodisomy of chromosome 22 with segmental isodisomy). This is the first case report of a patient with cb5r deficiency type I resulting from uniparental disomy and also discloses an alternate mechanism whereby this enzymatic disorder can be derived from a single parent. [Copyright &y& Elsevier]

• The first bioinformatic analysis of GEO in rosacea. • Both innate and adaptive immune responses were involved in the etiology of rosacea. • Five DEGs in the TLR signaling pathway as potential therapeutic target genes. Rosacea is a chronic inflammatory skin disease whose psychological consequences severely affect patient's quality of life. To identify candidate genes of rosacea for potential development of new target therapies. 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. 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. 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. [ABSTRACT FROM AUTHOR]

In this study, the anti-inflammatory mechanisms of Quercetin (Que) on atopic dermatitis (AD)-like skin lesions was examined. The left ear of mice was applied with MC903, followed by Que. administration daily on the ear for 8 days. Then macroscopic and histologic examination was performed to detect the severity of skin lesions. In the skin section of AD mice, we observed that Que. could reduce the expression of CCL17, CCL22, IL-4, IL-6, IFN-γ and TNF-α. In vitro, the anti-inflammatory effects of Que. were examined on human keratinocytes (HaCaT cells) treated with IFN-γ/TNF-α. To unveil the lncRNAs' regulatory role on Que-activated anti-inflammatory function, the next-generation high-throughput sequencing was performed in HaCat cells with or without Que. treatment, which profiled the expression of lncRNAs and mRNAs, the results illustrated that lnc-C7orf30–2, a lncRNA expressed differentially, was correlated with IL-6 expression. Silencing of lnc-C7orf30–2 by RiboTM lncRNA Smart Silencer proved its role on IL-6 expression. Therefore, the results here demonstrated that topical administration of Que. plays a beneficial role in controlling AD symptoms, which may serve as potential candidate for AD treatment. • The anti-inflammatory mechanisms of Quercetin (Que) on atopic dermatitis (AD)-like skin lesions was examined. • Que. plays a beneficial role in controlling AD symptoms in vivo and in vitro. • lnc-C7orf30–2, a lncRNA expressed differentially, is correlated with IL-6 expression. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies are a family of closely related but heterogeneous autoantibodies that may have different biological and pathogenic properties. The article investigates the distribution of six kinds of Antiphospholipid antibodies (aPL) in the serum of healthy volunteers. Whole peripheral blood samples of 82 healthy volunteers were drawn from blood donors with median age of 39.3 years. The findings suggest that healthy volunteers possess aPL. Some aPL are natural autoantibodies that are present in healthy individuals. Other aPL present in sera from healthy individuals are those that may be uncovered by heating sera at 56 degrees Celsius for 30 minutes.

Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth., Competing Interests: The author declares that there are no competing financial interests., (© 2024 Cheng et al.)

Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/sites/default/files/attachments/resources/2016/03/16-current-bmj-education-coi-form.pdf.

Competing Interests: Conflicts of interest The medical instrument for infrared thermotherapy is a patented device (Patent No: US 8,246,668 B2) owned by The First Hospital of China Medical University; Rui-Qun Qi, Xing-Hua Gao, and Hong-Duo Chen are original patent holders. The patent was transferred to and manufactured by Liaoning Yanyang Medical Instrument Co Ltd.

Competing Interests: Conflicts of interest The medical instrument for infrared thermotherapy is a patented device (Patent No: US 8,246,668 B2) owned by The First Hospital of China Medical University; Rui-Qun Qi, Xing-Hua Gao, and Hong-Duo Chen are original patent holders. The patent was transferred to and manufactured by Liaoning Yanyang Medical Instrument Co Ltd.

Background: Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo., Objective: This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients., Method: 48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd)., Results: Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p < 0.05). No difference was seen between Group A and Group B or Group A and Group C (p > 0.05). More patients complained higher pain score in Group A as compared with Group C (p < 0.05)., Conclusion: The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the efficacy and safety of resveratrol combined with ablative fractional CO 2  laser system (AFL) treating skin photoaging., Methods: Thirty-two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period., Results: All subjects in TG achieved improvements of their photoaging signs compared to pre-treatment both the laser side and the non-laser side at 6 months (p < 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p < 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p < 0.05). On the non-laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p < 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG., Conclusion: The resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL., (© 2021 Wiley Periodicals LLC.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)

Background: Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases., Purpose: To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients., Methods: Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies., Results: 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml., Conclusion: Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Yang, Hu, Zhang, Cai, Guo, Xiao, Chen, Gao and Qiao.)

Primary cutaneous localized amyloidosis (PCLA) is a pruritic disorder with no radical cure. We trialed a combined therapy of ablative fractionated CO2 laser, topical retinoid, corticosteroids and levovitamin C on five patients. All patients responded with no intolerant signs. Two-year follow-up visit showed no recurrence. This might be a effective method awaiting more samples for further stronger evidence.

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.

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 ± 989.10 vs. 4272.67 ± 918.50, 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 ± 0.02 vs. 0.24 ± 0.01, 0.31 ± 0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ± 0.01 vs. 0.30 ± 0.01, 0.51 ± 0.02, 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., (Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

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/cm 2 ), 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., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Interleukin (IL)‑18, a pro‑inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL‑18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild‑type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903‑treated WT mice; and iv) MC903‑treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD‑like 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 enzyme‑linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL‑1β, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT‑qPCR was performed to assess the mRNA levels of IL‑1β, IL‑4, IL‑9, STAT3, corticotropin‑releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase‑1 in the skin lesions. It was demonstrated that IL‑18 may function as a pleiotropic pro‑inflammatory cytokine in the development of AD‑like lesions. IL‑18 KO reduced aggravated AD‑like lesions induced by MC903, in part by upregulating Th2 cytokines. IL‑18 promoted the expression of FLG in the epidermis and CRHR2 in AD‑like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL‑18 deficiency alleviates AD‑induced lesions in mice.

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.

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., (Copyright © 2020 Lu, Jiang, Yuan, Jiang, Yang, Zhu, Sun, Qi, Liu, Wang, Wu, Gao and Chen.)

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 (H 2 O 2 )-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 H 2 O 2 -induced oxidative damage in PIG1 and PIG3V. Taken together, our study firstly demonstrates that PF resists H 2 O 2 -induced oxidative stress in melanocytes probably by activating JNK/Nrf2/HO-1 signaling, suggesting a potential therapeutic application of PF on vitiligo., (Copyright © 2020 Yuan, Lu, Wang, Feng, Jiang, Gao, Qi, Wu and Chen.)

Pomegranate phenolics have been reported to exert skin beneficial effects but their mechanisms of action remain unclear. Herein, we investigated a standardized commercial pomegranate extract (PE; Pomella®) and its phenolics including punicalagin (PA), ellagic acid (EA), and urolithin A (UA) for their protective effects against hydrogen peroxide (H 2 O 2 )-induced oxidative stress and cytotoxicity in human keratinocyte HaCaT cells. PE, PA, and EA reduced the production of H 2 O 2 -induced ROS in HaCaT cells by 1.03-, 1.37-, and 2.67-fold, respectively. PE, PA, and UA increased the viability of H 2 O 2 -stimulated HaCaT cells by 89.9, 94.9, and 90.0%, respectively. PE, PA, and UA reduced apoptotic cell populations by 3.39, 7.11, and 8.26%, respectively. In addition, PE, PA and UA decreased H 2 O 2 -stimulated caspase-3 level by 2.31-, 2.06-, and 2.68-fold, respectively. The ameliorative effects of this PE and its phenolics against the H 2 O 2 -induced oxidative stress and cytotoxicity in keratinocytes support their utilization as natural cosmeceuticals for skin health.
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Objectives: To explore potential effects of recombinant human fibroblast growth factor 20 (rhFGF20) in the growth of cultured mouse vibrissal follicles., Results: The growth of cultured mouse vibrissal follicles was significantly induced by rhFGF20 in a dose dependent pattern in the in vitro vibrissal follicle organ culture model. However, too high concentration of rhFGF20 could inhibit the growth of vibrissal follicles. We further demonstrated that rhFGF20 stimulated the proliferation of hair matrix cells and activated Wnt/β-catenin signaling pathway., Conclusions: The rhFGF20 might be a potential therapeutic agent to treat hair loss disorders.

Prostanoids, including prostaglandins (PGs) and thromboxane A2 (TXA2), are a family of lipid-derived autacoids that modulate many physiological systems and pathological contexts. Prostanoids are generated by sequential metabolism of arachidonic acid, catalysed by cyclo-oxygenase, to PGH2, which is then converted to PGD2, PGE2, PGF2α, PGI2 and TXA2, catalysed by their specific synthases. Recent evidence suggests that prostanoids play a role in regulating hair growth. The PGF2α analogue is Food and Drug Administration-approved in the US and routinely used to enhance the growth of human eyelashes. PGE2 is reported to protect from radiation-induced hair loss in mice. Conversely, PGD2 inhibits hair growth. This paper reviews the metabolism of prostanoids and the expression pattern of prostanoid receptors in hair follicles, focussing on their different and opposing effects on hair growth and the underlying mechanisms. This has potential clinical relevance in the treatment and prevention of hair disorders.

To assess the sociodemographic data and clinical information of outpatients affected by vitiligo in the northeast of China, vitiligo patients or guardians who presented to the clinic were invited to participate in an exploratory questionnaire. The questionnaire consisted of two sections related to vitiligo, including sociodemographic data and clinical information. A total of 983 vitiligo patients answered the questionnaire. The rates of female and male patients were comparable. The investigated patients were mostly young and middle-aged. Most patients suffered from vitiligo in childhood or young adulthood. Vitiligo vulgaris was the most common type of vitiligo in clinic and 53.0% of patients were categorized as body surface area (BSA) of 10% or less. In response to the latest treatment, 43.6% of patients achieved good response (completely stopped or almost disappeared). More patients at active stage showed good response than the patients at stable stage (χ 2 = 7.866, P < 0.05). Chronic comorbid condition(s) were observed in 12.6% of patients with BSA of more than 10%, whereas those were seen in 6.0% of patients with BSA of 10% or less (χ 2 = 12.969, P < 0.05). In conclusion, active vitiligo seems to respond better than stable vitiligo and complications with other autoimmune diseases more frequently observed in severe patients than mild patients. The current study presented a comprehensive understanding of vitiligo in the northeast of China., (© 2017 Japanese Dermatological Association.)

Interleukin (IL)-17 signaling serves an important role in the development and pathogenesis of psoriasis; a chronic skin disease characterized by increased dermal vascularity and the hyperproliferation of keratinocytes. microRNA (miR)‑203 is preferentially expressed in the skin and is an important regulator of keratinocyte differentiation. miR‑203 has been implicated in a number of skin diseases, including psoriasis. However, the role of miR‑203 in IL‑17‑induced vascular endothelial growth factor (VEGF) secretion has yet to be elucidated. The present study demonstrated that miR‑203 expression was upregulated in the ears of IL‑17‑stimulated mice and IL‑17‑treated HaCaT cells. In addition, the IL‑17‑induced increase in miR‑203 expression activated the Janus kinase/signal transducer and activator of transcription signaling pathway and promoted VEGF secretion in HaCaT cells. Furthermore, miR‑203 was observed to bind to the 3'‑untranslated region of suppressor of cytokine signaling 3 (SOCS3) and inhibited SOCS3 expression. The results suggest that miR‑203 expression may be upregulated by IL‑17 stimulation, and miR‑203 is a positive regulator of IL‑17‑induced VEGF secretion. The present study may support potential therapeutic strategies for the treatment of psoriasis.

Background: Stable non-segmental vitiligo is often resistant to conventional therapies., Objectives: The purpose of this study was to investigate the effect of three types of fractional lasers in the treatment of stable non-segmental vitiligo., Materials & Methods: Twenty patients were enrolled in the study. The vitiligo lesions of each patient were divided into four treatment parts, and all parts were treated with narrowband ultraviolet-B (NB-UVB). Three of the four parts were respectively treated with three types of fractional lasers (two ablative 10,600-nm CO 2 lasers and one non-ablative 1,565-nm laser), followed by topical betamethasone solution application. The treatment period lasted six months. Efficacy and satisfaction were respectively assessed by dermatologists and patients., Results: The ablative CO 2 lasers, in combination with topical betamethasone solution and NB-UVB, achieved marked to excellent improvement on white patches assessed by dermatologists. Patients showed high satisfaction scores for the treatments. The non-ablative 1,565-nm fractional laser did not provide any further benefit in the treatment of vitiligo. No severe adverse events developed for any of the treatments., Conclusion: The treatment protocol with ablative CO 2 lasers, in combination with topical betamethasone solution and NB-UVB, was suitable for stable non-segmental vitiligo. For vitiligo, the ablative fractional CO 2 laser is more effective than the non-ablative fractional laser.

Background: Although pulsed dye laser (PDL) has long been regarded as the gold standard in treating port-wine stain (PWS), advanced PWS with deeper coloration may display resistance because of limited penetration depth of 585 or 595-nm light. Recently, a dual-wavelength laser system has been reported to achieve pronounced fading in many patients., Objective: The objective was to evaluate the efficacy and safety of a dual-wavelength laser device in treatment of neck and facial PWS in a direct side-by-side comparison., Methods: Sixteen Chinese patients with neck and/or facial PWSs were enrolled in the study. All lesions were randomly divided into two area, treated area and adjacent untreated area. Five successive treatments using a dual-wavelength laser system (595-nm PDL combined with 1,064-nm Nd:YAG laser) were delivered on treated areas at 4- to 6-week intervals. The adjacent area was not treated as self control. Two blinded dermatologists evaluated the clinical changes by comparing the before and after photos. Erythema index (EI) values were measured with a non-invasive instrument., Results: After five sessions of treatment, over 62.5% (10/16) patients achieved more than 50% (moderate or significant) improvement. The efficacy maintained at the 3-month follow-up visit. The values of EI on treated area showed a significant decrease. Adverse effects of treated area were limited., Conclusion: Using this split-face module, the dual-wavelength laser system is proved to be effective and well tolerated in treating neck and facial PWSs in Chinese patients. Adverse effects were minimal and acceptable.