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Many studies have recently used several deep learning methods for detecting skin cancer. However, hyperspectral imaging (HSI) is a noninvasive optics system that can obtain wavelength information on the location of skin cancer lesions and requires further investigation. Hyperspectral technology can capture hundreds of narrow bands of the electromagnetic spectrum both within and outside the visible wavelength range as well as bands that enhance the distinction of image features. The dataset from the ISIC library was used in this study to detect and classify skin cancer on the basis of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis (SK). The dataset was divided into training and test sets, and you only look once (YOLO) version 5 was applied to train the model. The model performance was judged according to the generated confusion matrix and five indicating parameters, including precision, recall, specificity, accuracy, and the F1-score of the trained model. Two models, namely, hyperspectral narrowband image (HSI-NBI) and RGB classification, were built and then compared in this study to understand the performance of HSI with the RGB model. Experimental results showed that the HSI model can learn the SCC feature better than the original RGB image because the feature is more prominent or the model is not captured in other categories. The recall rate of the RGB and HSI models were 0.722 to 0.794, respectively, thereby indicating an overall increase of 7.5% when using the HSI model.

Che-Hsing Li,1,2,&ast; Jiunn-Liang Ko,1,3,4,&ast; Yu-Ping Hsiao,5,6 Ming-Hung Tsai,7 Yen-Chein Lai,8 I-Lun Hsin,3,4 Yu-Ting Kang,3,4 Gwo-Tarng Sheu,1,3,4 Wea-Lung Lin,6,9 Ming-Fang Wu1,4,6 1Divisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan; 2Graduate Program in Immunology & Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA; 3Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; 4CSMU Lung Cancer Research Center, Chung Shan Medical University, Taichung, 402, Taiwan; 5Division of Dermatology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan; 6School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; 7Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40447, Taiwan; 8Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan; 9Department of Pathology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan&ast;These authors contributed equally to this workCorrespondence: Ming-Fang WuDivisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, 110, Sec. 1, Jianguo N. Road, Taichung, 40201, TaiwanTel +886-4-24739595#34711Email mfwu0111@gmail.comPurpose: Pemetrexed-based chemotherapy (Pem-C) is the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, limited tumor-associated proteins in blood are available to predict pemetrexed response and/or survival.Patients and Methods: Plasma samples from three responders and three nonresponders with stage IIIB–IV NSCLC were collected prior to Pem-C and analyzed using Proteome ProfilerTM Human XL Oncology Array to detect 84 oncology-related proteins. The plasma concentrations of cathepsin S, endoglin (ENG), and matrix metalloproteinases 3 and 9 in 71 patients with advanced NSCLC treated with Pem-C were further measured using enzyme-linked immunosorbent assay based on the remarkable differences in the four proteins between responders and nonresponders in the array results.Results: Pem-C responders had significantly higher ENG levels but not the other three markers than nonresponders (mean ENG level: 27.1 ± 7.4 vs 22.3 ± 6.9, p < 0.01). High ENG concentration was correlated with improved progression-free survival (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.31– 0.86, p < 0.01) and overall survival (HR: 0.55, 95% CI: 0.32– 0.94, p < 0.05) in patients treated with Pem-C, and the ENG level was an independent factor in our cohort (HR: 0.54, 95% CI: 0.33– 0.89, p < 0.05). ENG concentration in Pem-C responders also significantly increased at the time of best response (p < 0.05).Conclusion: Cumulatively, this study reveals that ENG is correlated with Pem-C responsiveness in patients, which indicates the potential use of plasma ENG levels as a non-invasive biomarker for pemetrexed-based treatment in patients with non-squamous NSCLC.Keywords: endoglin, pemetrexed-based therapy, prognostic factor, non-squamous non-small cell lung cancer, biomarker

Angiopoietin-like protein 4 (ANGPTL4) is a hypoxia-induced gene, and its high expression is associated with poor prognosis and promotion of tumour progression in several cancers. Some studies reported that ANGPTL4 is affected by epigenetic regulation. Our previous results demonstrated that ANGPTL4 is highly expressed in most lung cancer cell lines than in normal cell lines and is upregulated by HIF-1α accumulation under NiCl2 exposure. The accurate role of ANGPTL4 and its methylation status caused by nickel in the lung carcinogenesis is not fully explored yet. In this study, we found that ANGPTL4 and HIF-1α in lung adenocarcinoma (LUAD) tissues were significantly upregulated compared with those in normal tissues in The Cancer Genome Atlas (TCGA) cohort (p < 0.001). The ANGPTL4 expression was statistically correlated to advanced stage (p = 0.019) and N value (p = 0.002). The Kaplan-Meier analysis revealed that ANGPTL4 and HIF-1α expression levels were independently associated with the 5-year survival of patients with LUAD in TCGA database and immunohistochemistry staining. In vitro experiments indicated that ANGPTL4 was upregulated by the demethylation agent. The methylation-specific PCR and bisulfite sequencing assessed the methylation status of the ANGPTL4 promoter, and results showed that NiCl2-treated cells had low ANGPTL4 methylation status. We further demonstrated that the DNA demethylase, TET1, was significantly increased under NiCl2 exposure. The knockdown of TET1 expression repressed the NiCl2-induced ANGPTL4. We also showed that nickel-induced TET1 was stimulated by HIF-1α. Our work established ANGPTL4 as a potential oncogene that contributes to lung cancer progression and nickel-elicited carcinogenesis.

Background Chronic exposure to ultraviolet (UV) rays causes severe skin damage by inducing oxidative stress and inflammation. Identifying a safe and natural substance for skin protection is a crucial research goal. Objective The aim of this study was to clarify the effects of genistein on skin inflammation and photoaging by using 3 models (humans: skin parameters; animals: wrinkle formation; and cells: anti-inflammatory effects). Methods Food frequency questionnaire data and serum and skin parameter data from 120 volunteers (a group with a genistein-rich diet [RG group] and a control group). Human keratinocytes were pretreated with genistein before ultraviolet B (UVB) irradiation. Genistein was topically applied to the dorsal skin of rats. Results The blood samples of the RG group had lower serum uric acid levels and blood urea nitrogen levels. The dynamic elasticity level in the RG group was higher than that in the controls. Genistein pretreatment suppressed the expression of proinflammatory cytokines (CXCL1, IL-1, MIF, and PLANH1) and the proteins released by UVB-treated keratinocytes. Topical application of genistein to the dorsal skin of rats reduced the severity of UVB-induced wrinkling. Both intake and topical application of genistein combated UVB-induced inflammation and aging. Conclusions Genistein could be used as a safe and natural compound for use in novel anti-inflammatory agents for topical application. Graphical abstract The experimental design procedure, including the skin parameter and blood serum measurements of 137 participants. Genistein-rich compounds provide protection against UVB-induced inflammation, as determined using in vitro and in vivo animal model experiments.

Burns can cause cell death and irreversible tissue damage. We examined the pathway of human dermis fibroblasts cell death caused by skin burns and the roles of chloroquine in human skin keratinocytes HaCaT wound healing. Western blot assays were performed to assess expression of proteins associated with autophagy, apoptosis, and endoplasmic reticulum stress in skin cells following burns. Changes in apoptosis-related proteins were assessed using flow cytometry, and wound cell migration was examined using wound healing assays. The burn animal model was used to test whether chloroquine would promote wound healing. In human burned fibroblasts, expression of LC3B-II and Cleave-caspase-7 was increased, whereas expression of Beclin-1, p62, and Grp78 was decreased. Severe burn induced ER stress and ERK phosphorylation, but PD98059 or necrostatin-1 treatment cells did not affect expression of autophagy LC3B-II protein and can induce apoptosis. Even though added with TGF-β and FGF did not repair autophagy caused by burns. Suggesting that autophagy and apoptosis were involved in heat-injured mechanism. Recombinant Wnt3a protein can help restore expression of β-catenin which reduced following burns in keratinocytes. Wnt3a protein can promote migration of keratinocytes after burns. Interesting, chloroquine increased expression of LC3B-II protein and restored cell migration activity after 24 h of burns. Consistently, surgical dressing containing chloroquine promoted wound healing in a burn animal mode. Autophagy and Wnt/β-catenin is two signalling pathways that participate in cell repair and wound healing in human fibroblasts, keratinocytes. Surgical dressing containing chloroquine can recover wound healing in burned rats.

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity, depleting Escherichia-Shigella and the Enterobacteriaceae family, and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut–kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity; depleting Escherichia-Shigella and the Enterobacteriaceae family; and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut–kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.

Nickel compounds are associated with lung and skin cancer incidence increase and accumulation of nickel in the body contributes to carcinogenesis. Upregulation of certain integrins in the primary tumor is associated with cancer metastasis and poor prognosis. However, the molecular mechanisms of nickel-induced cancer metastasis are still unclear. The purpose of the present study was to investigate the effects of nickel chloride (NiCl2 ) on the progression of cancer during metastasis. The results of showed that NiCl2 induces the expression of integrin β3 mRNA and protein in a dose- and time-dependent manner. Inhibition of integrin αvβ3 activation by ITGB3 ligand mimetics and GR144053, as well as downregulation of ITGB3 by lentiviral shRNA gene silencing, diminished NiCl2 -induced secretion of vascular endothelial growth factor-a (VEGF-a). Furthermore, pretreatment with type I TGF-β receptor inhibitor, SB525334, suppressed the expression of ITGB3 at cell surface and secretion of VEGF-a in NiCl2 -treated cells. In conclusion, NiCl2 induces the expression of ITGB3 through TGF-β signaling activation, followed by increasing VEGF-a secretion, revealing a novel role for ITGB3 in nickel compound-induced cancer metastasis and tumor angiogenesis.

Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.

Background: Facial angiofibromas may be present since early childhood in individuals with tuberous sclerosis complex (TSC), causing substantial cosmetic disfigurement. Current therapies are partially effective, but they are uncomfortable, produce scarring, and are especially expensive. Objective: The aim of the present study was to evaluate the efficacy of oral everolimus for TSC-associated angiofibromas. Methods: This retrospective study included TSC patients being treated with oral everolimus for subependymal giant cell astrocytomas (SEGAs) and angiomyolipomas (AMLs). We recorded the changes in facial angiofibromas. Changes in the Angiofibroma Grading Scale (AGS) indicators were recorded according to erythema, average lesion size, lesion density, and percent involvement on the forehead, nose, cheeks, and chin. The scores were recorded before and after the administration of oral everolimus. Results: Twenty-one patients being treated with oral everolimus were enrolled in this study. The mean age was 20.5 years (range 11–44 years, 4 males, and 17 females). The mean dose of oral everolimus was 3.6 mg/day. Clinically meaningful and statistically significant improvement was observed in erythema (p = 0.001), average lesion size (p < 0.001), lesion density (p < 0.001), and percent involvement (p < 0.001). Changes in the AGS findings were statistically significant on the forehead (p = 0.001), nose (p < 0.001) cheeks (p < 0.001), and chin (p = 0.004). Conclusion: Everolimus shows evident improvement and is approved for TSC-associated SEGAs and AMLs. The current study demonstrated the efficacy of oral everolimus in reducing facial angiofibromas, showing the parallel benefits of the treatment protocol for TSC.

α-(1,6)-fucosyltransferase 8 (FUT8) is implicated in the pathogenesis of several malignancies, but its role in psoriasis is poorly understood. In this study, we show that FUT8 remodeling of EGFR plays a critical role in the development of psoriasis phenotypes. Notably, elevated FUT8 expression was associated with disease severity in the lesional epidermis of a patient with psoriasis. FUT8 gain of function promoted HaCaT cell proliferation, whereas short hairpin FUT8 reduced cell proliferation and induced a longer S phase with downregulation of cyclin A1 expression. Furthermore, cell proliferation, which is controlled by the activation of EGFR, was shown to be regulated by FUT8 core fucosylation of EGFR. Short hairpin FUT8 significantly reduced EGFR/protein kinase B signaling and slowed EGF‒EGFR complex trafficking to the perinuclear region. Moreover, short hairpin FUT8 reduced ligand-induced EGFR dimerization. Overactivated EGFR was observed in the lesional epidermis of both human patient and psoriasis-like mouse model, whereas conditional knockout of FUT8 in an IL-23 psoriasis-like mouse model ameliorated disease phenotypes and reduced EGFR activation in the epidermis. These findings implied that elevated FUT8 expression in the lesional epidermis is implicated in the development of psoriasis phenotypes, being required for EGFR overactivation and leading to keratinocyte hyperproliferation.

A highly sensitive photoelectrochemical (PEC) biosensor without external bias was developed in this study. The biosensor was configured with a p-Cu2O and n-ZnO heterostructure. Hexamethylenetetramine (HMTA) and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was used to improve the crystal structure of Cu2O and ZnO and reduce the defects in the Cu2O/ZnO interface. This fabrication method provided the highly crystallized Cu2O/ZnO structure with excellent electrical property and photoresponse in visible light. The structure was applied to a biosensor for detecting two different cancerous levels of esophageal cells, namely, OE21 and OE21-1, with a high gain in photocurrent (5.8 and 6.2 times, respectively) and a low detection limit (3000 cells in 50 μL). We believe that such a p-n heterojunction PEC biosensor could advance biosensor development and provide a promising candidate for biomedical applications.

Background In terms of melanoma, recent advances have been made in target therapies and immune checkpoint inhibitors, but durable remission is rare. Ganoderma immunomodulatory proteins (GMI) induce a cytotoxic effect in cancer cells via autophagy. However, the role of GMI in melanoma is not clear. Purpose The aims of this study are to investigate the inhibiting effects of GMI combined with chidamide on survival and metastases of melanoma cells via integrin-related signaling pathway and to propose strategies for combining GMI and chidamide using animal model. Methods Cell viability was measured by cell CCK-8. The activities of apoptosis- and migration-related proteins were detected on Western blot. Flow cytometry was used to analyze cell cycle distribution and sub-G1 fraction in treated melanoma cells. To evaluate the activity of combination GMI and chidamide treatment, an in vivo anti-tumor metastasis study was performed. Results GMI combined with chidamide additively induced apoptosis. GMI inhibited the expressions of Integrin α5, αV, β1, and β3. The level of p-FAK was inhibited by GMI. Combination treatment of GMI and chidamide decreased survivin and increased cleaved caspase-7 and LC3 II/I. Integrin-αV overexpression activated p-FAK pathways in A375.S2 cells. GMI significantly inhibited cell growth and migration of A375.S2 cells on wound healing assay. In vivo, GMI combined with chidamide suppressed distal tumor metastasis. Conclusion GMI inhibits the migration and growth of melanoma cells via integrin-related signaling pathway. GMI and chidamide induces apoptosis. In vivo, GMI and chidamide additively reduce distant metastases. GMI and chidamide are potential immunotherapeutic adjuvant for metastatic melanoma.

Background Glycolic acid (GA), commonly present in fruits, has been used to treat dermatological diseases. Extensive exposure to solar ultraviolet B (UVB) irradiation plays a crucial role in the induction of skin inflammation. The development of photo prevention from natural materials represents an effective strategy for skin keratinocytes. Objective The aim of this study was to investigate the molecular mechanisms underlying the glycolic acid (GA)-induced reduction of UVB-mediated inflammatory responses. Methods We determined the effects of different concentrations of GA on the inflammatory response of human keratinocytes HaCaT cells and C57BL/6J mice dorsal skin. After GA was topically applied, HaCaT and mice skin were exposed to UVB irradiation. Results GA reduced the production of UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators [interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP-1)] at both mRNA and protein levels. GA inhibited the UVB-induced promoter activity of NF-κB in HaCaT cells. GA attenuated the elevation of senescence associated with β-galactosidase activity but did not affect the wound migration ability. The topical application of GA inhibited the genes expression of IL-1β, IL-6, IL-8, COX-2, and MCP-1 in UVB-exposed mouse skin. The mice to UVB irradiation after GA was topically applied for 9 consecutive days and reported that 1–1.5% of GA exerted anti-inflammatory effects on mouse skin. Conclusion We clarified the molecular mechanism of GA protection against UVB-induced inflammation by modulating NF-κB signaling pathways and determined the optimal concentration of GA in mice skin exposed to UVB irradiation.

Ketoconazole, an antifungal agent, has been used to inhibit hormone synthesis in types of prostate and breast cancer. Immunomodulatory proteins of Ganoderma microsporum (GMI) inhibit the tumor necrosis factor-α- and epidermal growth factor-induced metastatic ability of lung cancer cells. Cutaneous malignant melanoma is a highly invasive and metastatic skin cancer. However, to the best of our knowledge, there is limited understanding regarding the effects of ketoconazole and GMI on melanoma. The current study aimed to investigate the inhibitory effects of GMI combined with ketoconazole on melanoma survival and metastasis. The effects of GMI combined with ketoconazole on the viability, migration and protein expression of melanoma cells were determined by MTT assay, Boyden chamber assay and western blot analysis, respectively. The expression of monocyte chemoattractant protein-1 (MCP-1) was investigated by enzyme-linked immunoabsorbent assay. The present results indicate that ketoconazole enhances the GMI-induced decrease in proliferation and migration of A375.S2 melanoma cells in a concentration-dependent manner. Ketoconazole was identified to reduce the level of GMI-induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK)-α and autophagy; however, ketoconazole did not affect p-AMPK-β levels in A375.S2 cells. In addition, ketoconazole and dorsomorphin dihydrochloride, an AMPK inhibitor, were revealed to reduce MCP-1 secretion in A375.S2 cells. In summary, the present study revealed that ketoconazole enhances GMI-inhibited proliferation and migration of A375.S2 melanoma cancer cells, and inhibits the secretion of MCP-1.

5-Fluorouracil (5-FU) is used in the treatment of head and neck cancer patients. However, adverse effects experienced such as mucositis and poor appetite may lead to interruption in chemotherapy. The aim of this study is to evaluate the efficacy of GMI, one fungal immunomodulatory protein found in Ganoderma microsporum, for mucositis induced by 5-FU in a mouse model. Mice were administered 5-FU intraperitoneally for 4 days per cycle for a total of 2 chemotherapy cycles. In addition, mice were pretreated with GMI or phosphate-buffered saline 3 days before 5-FU intraperitoneal injection and daily until day 14. On histological analysis, GMI prevented 5-FU-induced damage to the intestinal mucosa and tongue epithelium. We also demonstrated that GMI enhanced the cytotoxicity of 5-FU in 2 oral cancer cell lines, while GMI could not promote this effect in an oral normal cell. In conclusion, GMI alleviates 5-FU-induced damage and decelerates cell death in normal alimentary tract tissue.

An artificial intelligence algorithm to detect mycosis fungoides (MF), psoriasis (PSO), and atopic dermatitis (AD) is demonstrated. Results showed that 10 s was consumed by the single shot multibox detector (SSD) model to analyze 292 test images, among which 273 images were correctly detected. Verification of ground truth samples of this research come from pathological tissue slices and OCT analysis. The SSD diagnosis accuracy rate was 93%. The sensitivity values of the SSD model in diagnosing the skin lesions according to the symptoms of PSO, AD, MF, and normal were 96%, 80%, 94%, and 95%, and the corresponding precision were 96%, 86%, 98%, and 90%. The highest sensitivity rate was found in MF probably because of the spread of cancer cells in the skin and relatively large lesions of MF. Many differences were found in the accuracy between AD and the other diseases. The collected AD images were all in the elbow or arm and other joints, the area with AD was small, and the features were not obvious. Hence, the proposed SSD could be used to identify the four diseases by using skin image detection, but the diagnosis of AD was relatively poor.

AHAs (α-hydroxy acids), including glycolic acid (GA), have been widely used in cosmetic products and superficial chemical peels. Inflammasome complex has been shown to play critical roles in inflammatory pathways in human keratinocytes. However, the anti-inflammatory mechanism of GA is still unknown. The aim of this study is to investigate the relationship between the expression of the inflammasome complex and epigenetic modification to elucidate the molecular mechanism of the anti-inflammatory effect of GA in HaCaT cells. We evaluated NLRP3, NLRC4, AIM2, and ASC inflammasome complex gene expression on real-time polymerase chain reaction (PCR). Methylation changes were detected in these genes following treatment with DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-Aza) with or without the addition of GA using methylation-specific PCR (MSP). GA inhibited the expressions of these inflammasome complex genes, and the decreases in the expressions of mRNA were reversed by 5-Aza treatment. Methylation was detected in NLRC4 and ASC on MSP, but not in NLRP3 or AIM2. GA decreased NLRC4 and ASC gene expression by increasing not only DNA methyltransferase 3B (DNMT-3B) protein level, but also total DNMT activity. Furthermore, silencing of DNMT-3B (shDNMT-3B) increased the expressions of NLRC4 and ASC. Our data demonstrated that GA treatment induces hypermethylation of promoters of NLRC4 and ASC genes, which may subsequently lead to the hindering of the assembly of the inflammasome complex in HaCaT cells. These results highlight the anti-inflammatory potential of GA-containing cosmetic agents in human skin cells and demonstrate for the first time the role of aberrant hypermethylation in this process.

Casticin, a polymethoxyflavone occurring in natural plants, has been shown to have anticancer activities. In the present study, we aims to investigate the anti-skin cancer activity of casticin on melanoma cells in vitro and the antitumor effect of casticin on human melanoma xenografts in nu/nu mice in vivo. A flow cytometric assay was performed to detect expression of viable cells, cell cycles, reactive oxygen species production, levels of [Formula: see text] and caspase activity. A Western blotting assay and confocal laser microscope examination were performed to detect expression of protein levels. In the in vitro studies, we found that casticin induced morphological cell changes and DNA condensation and damage, decreased the total viable cells, and induced G2/M phase arrest. Casticin promoted reactive oxygen species (ROS) production, decreased the level of [Formula: see text], and promoted caspase-3 activities in A375.S2 cells. The induced G2/M phase arrest indicated by the Western blotting assay showed that casticin promoted the expression of p53, p21 and CHK-1 proteins and inhibited the protein levels of Cdc25c, CDK-1, Cyclin A and B. The casticin-induced apoptosis indicated that casticin promoted pro-apoptotic proteins but inhibited anti-apoptotic proteins. These findings also were confirmed by the fact that casticin promoted the release of AIF and Endo G from mitochondria to cytosol. An electrophoretic mobility shift assay (EMSA) assay showed that casticin inhibited the NF-[Formula: see text]B binding DNA and that these effects were time-dependent. In the in vivo studies, results from immuno-deficient nu/nu mice bearing the A375.S2 tumor xenograft indicated that casticin significantly suppressed tumor growth based on tumor size and weight decreases. Early G2/M arrest and mitochondria-dependent signaling contributed to the apoptotic A375.S2 cell demise induced by casticin. In in vivo experiments, A375.S2 also efficaciously suppressed tumor volume in a xenotransplantation model. Therefore, casticin might be a potential therapeutic agent for the treatment of skin cancer in the future.

Wound infection extends the duration of wound healing and also causes systemic infections such as sepsis, and, in severe cases, may lead to death. Early prevention of wound infection and its appropriate treatment are important. A photoreactive modified gelatin (GE-BTHE) was synthesized by gelatin and a conjugate formed from the 3,3&prime, 4,4&prime, benzophenone tetracarboxylic dianhydride (BTDA) and the 2-hydroxyethyl methacrylate (HEMA). Herein, we investigated the photocurable polymer solution (GE-BTHE mixture) containing GE-BTHE, poly(ethylene glycol) diacrylate (PEGDA), chitosan, and methylene blue (MB), with antimicrobial functions and photodynamic antimicrobial chemotherapy for wound dressing. This photocurable polymer solution was found to have fast film-forming property attributed to the photochemical reaction between GE-BTHE and PEGDA, as well as the antibacterial activity in vitro attributed to the ingredients of chitosan and MB. Our in vivo results also demonstrated that untreated wounds after 3 days had the same scab level as the GE-BTHE mixture-treated wounds after 20 s of irradiation, which indicates that the irradiated GE-BTHE mixture can be quickly transferred into artificial scabs to protect wounds from an infection that can serve as a convenient excisional wound dressing with antibacterial efficacy. Therefore, it has the potential to treat nonhealing wounds, deep burns, diabetic ulcers and a variety of mucosal wounds.

Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway.

Electrochemical-metallization-type resistive random access memories (ReRAMs) show promising performance as next-generation nonvolatile memory. In this paper, the Cu chemical displacement technique (CDT) is used to form the bottom electrode of ReRAM devices. Compared with conventional deposition methods, the Cu-CDT method has numerous advantages for ReRAM fabrication, including low cost, low temperature fabrication, and the provision of unconsolidated Cu film and large surface roughness. Moreover, the Cu-CDT method is a favorable candidate for overcoming the Cu etching problem and is thus suitable for fabricating ReRAM devices. Using this technique, the surface morphology of a thin Cu film can be easily controlled. The obtained results show that the electric fields during the Forming and SET operations decreased, and the on-state current increased in the RESET operation, as the Cu-CDT displacement time was increased. The Cu-CDT samples exhibited a low operation field, large memory window (>106), and excellent endurance switching cycle characteristics. Moreover, this paper proposes a model to explain the electrical characteristics of ReRAM, which are dependent on the surface morphology.

In this study, a polyimide (PI) thin film was synthesized as a resistive layer for creating resistive random access memory (ReRAM). The switch between high- and low-resistance states is caused by the formation and dissociation of dipole direction and Schottky barrier. The impact of imidization on memory properties was evaluated in detail by clarifying the transmission mechanism, and reliability properties including retention and endurance were improved using thermal imidization. In addition, the proposed PI-based ReRAM demonstrated superior performance levels compared with those of electrochemical-metallization-based and valence-change-based ReRAMs, including higher RON/ROFF ratio (> 107) and lower operation energy (

Background Atopic dermatitis (AD) is the single most common allergic disease in children. STAT6 has been noted as a hub molecule in IL-4 mediated response and AD pathogenesis. However, the association between STAT6 genetic variants and childhood AD has never been thoroughly examined. Objective We investigate the association between STAT6 genetic variants and childhood AD risk in Taiwanese population. Methods We used data from the Han Chinese in Beijing genome panel of International HapMap Project and the Taiwan Children Health Study cohort to investigate the association of STAT6 genetic variants and childhood AD risks. Four tagged SNPs were selected from HapMap database and rs324011 was most significantly associated with childhood AD. Subsequently, deep sequencing around rs324011 and unconditional/conditional logistic models were applied. Results rs324011 showed statistical significance for the occurrence of childhood AD (OR: 1.23; 95% CI: 1.01–1.51) and rs167769 showed borderline statistical significance (OR: 1.21; 95% CI: 0.99–1.49). Likelihood ratio tests revealed that haplotypes (rs167769/rs324011) were associated with childhood AD (global p = 0.0018). T alleles of two STAT6 intron2 SNPs, rs324011 and rs167769, increased STAT6 promoter activity significantly in luciferase reporter assay. Conclusion T allele of rs324011 in STAT6 would increase the risk of AD occurrence in children. Haplotypes of rs324011/rs167769 were also significantly associated with childhood AD in Taiwanese population.

A limited copper (Cu)-source Cu:SiO2 switching layer composed of various Cu concentrations was fabricated using a chemical soaking (CS) technique. The switching layer was then studied for developing applications in resistive random access memory (ReRAM) devices. Observing the resistive switching mechanism exhibited by all the samples suggested that Cu conductive filaments formed and ruptured during the set/reset process. The experimental results indicated that the endurance property failure that occurred was related to the joule heating effect. Moreover, the endurance switching cycle increased as the Cu concentration decreased. In high-temperature tests, the samples demonstrated that the operating (set/reset) voltages decreased as the temperature increased, and an Arrhenius plot was used to calculate the activation energy of the set/reset process. In addition, the samples demonstrated stable data retention properties when baked at 85 °C, but the samples with low Cu concentrations exhibited short retention times in the low-resistance state (LRS) during 125 °C tests. Therefore, Cu concentration is a crucial factor in the trade-off between the endurance and retention properties; furthermore, the Cu concentration can be easily modulated using this CS technique.

Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA induced apoptosis based on the observations of DAPI staining, DNA fragmentation, and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs). Flow cytometric assays also showed that MA increased the production of mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was significantly decreased whereas extracellular acidification rate (ECAR) was increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic reticulum stress associated protein expression such as GRP78, GADD153, and ATF6α. We demonstrated that MA had anti-proliferative effect in HaCaT cell through the inhibition of cell cycle progression at G0/G1, and the induction of programmed cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.