Molecular Triplet Generation Enabled by Adjacent Metal Nanoparticles.

High-efficiency generation of spin-triplet states in organic molecules is of great interest in diverse areas such as photocatalysis, photodynamic therapy, and upconversion photonics. Recent studies have introduced colloidal semiconductor nanocrystals as a new class of photosensitizers that can efficiently transfer their photoexcitation energy to molecular triplets. Here, we demonstrate that metallic Ag nanoparticles can also assist in the generation of molecular triplets in polycyclic aromatic hydrocarbons (PAHs), but not through a conventional sensitization mechanism. Instead, the triplet formation is mediated by charge-separated states resulting from hole transfer from photoexcited PAHs (anthracene and pyrene) to Ag nanoparticles, which is established through the rapid formation and subsequent decay of molecular anions revealed in our transient absorption measurements. The dominance of hole transfer over electron transfer, while both are energetically allowed, could be attributed to a Marcus inverted region of charge transfer. Owing to the rapid charge separation and the rapid spin-flip in metals, the triplet formation yields are remarkably high, as confirmed by their engagement in production of singlet oxygen with a quantum efficiency reaching 58.5%. This study not only uncovers the fundamental interaction mechanisms between metallic nanoparticles and organic molecules in both charge and spin degrees of freedom but also greatly expands the scope of triplet "sensitization" using inorganic nanomaterials for a variety of emerging applications.

Age and urban-rural disparities in cutaneous melanoma mortality rates in the United States during the COVID-19 pandemic.

Most recent studies on the coronavirus disease 2019 (COVID-19) pandemic and cutaneous melanoma (CM) focused more on delayed diagnosis or advanced presentation. We aimed to ascertain mortality trends of CM between 2012 and 2022, focusing on the effects of the COVID-19 pandemic. In this serial population-based study, the National Vital Statistics System dataset was queried for mortality data. Excess CM-related mortality rates were estimated by calculating the difference between observed and projected mortality rates during the pandemic. Totally there were 108,853 CM-associated deaths in 2012-2022. CM-associated mortality saw a declining trend from 2012 to 2019 overall. However, it increased sharply in 2020 (ASMR 3.73 per 100,000 persons, 5.95% excess mortality), and remained high in 2021 and 2022, with the ASMRs of 3.82 and 3.81, corresponding to 11.17% and 13.20% excess mortality, respectively. The nonmetro areas had the most pronounced rise in mortality with 12.20% excess death in 2020, 15.33% in 2021 and 20.52% in 2022, corresponding to a 4-6 times excess mortality risk compared to large metro areas during the pandemic. The elderly had the most pronounced rise in mortality, but the mortality in the younger population was reduced.

Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress.

Introduction: The new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib. Methods: hydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS. Results: Deu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis. Conclusion: Deu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.

Serine deficiency exacerbates psoriatic skin inflammation by regulating S-adenosyl methionine-dependent DNA methylation and NF-κB signalling activation in keratinocytes.

BACKGROUND: Serine metabolism is crucial for tumour oncogenesis and immune responses. S-adenosyl methionine (SAM), a methyl donor, is typically derived from serine-driven one-carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear. OBJECTIVES: To investigate the association between serine metabolism and psoriatic skin inflammation. METHODS: Clinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism-regulated psoriatic keratinocyte inflammation. An imiquimod (IMQ)-induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation. RESULTS: The expression of serine synthesis pathway enzymes, including the first rate-limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic-related signalling pathways, including the tumour necrosis factor-alpha (TNF-α) signalling pathway, interleukin (IL)-17 signalling pathway and NF-κB signalling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL-6 in keratinocytes with or without IL-17A, IL-22, IL-1α, oncostatin M and TNF-α (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL-6 by inhibiting SAM-dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL-6 by increasing the activation of NF-κB via SAM inhibition. SAM treatment effectively alleviated IMQ-induced psoriasis-like skin inflammation in mice. CONCLUSIONS: Our study revealed the crucial role of PHGDH in antagonising psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis.

Excess psoriasis and psoriatic arthritis mortality during the COVID-19 pandemic in the United States: A nationwide population-based study from 2010 to 2021.

BACKGROUND: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. OBJECTIVES: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic. METHODS: We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. RESULTS: Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%-17.9%) and 2021 (19.8%, 95% CI: 18.0%-21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA. CONCLUSIONS: Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.

Inhibition of Serum- and Glucocorticoid-Regulated Protein Kinase-1 Aggravates Imiquimod-Induced Psoriatic Dermatitis and Enhances Proinflammatory Cytokine Expression through the NF-kB Pathway.

Although the anti-inflammatory effect of serum- and glucocorticoid-regulated protein kinase 1 (SGK1) has been established in other diseases, the possible regulatory role of SGK1 in psoriasis and the underlying molecular mechanisms remain largely unknown. In this study, we found that SGK1 expression was decreased in macrophages from patients with psoriasis. Moreover, a specific pharmacological SGK1 inhibitor, EMD638683, significantly enhanced imiquimod-mediated toll-like receptor 7/8 activity and proinflammatory cytokine production in RAW264.7 cells, and this result was confirmed by Sgk1 small interfering RNA. Further mechanistic data showed that SGK1 inhibition increased the phosphorylation of Bruton's agammaglobulinemia tyrosine kinase; moreover, Bruton's agammaglobulinemia tyrosine kinase inhibition abrogated the proinflammatory effects of the SGK1 inhibitor on toll-like receptor 7/8 activation, thereby validating that SGK1 inhibition enhances the toll-like receptor 7/8 pathway by increasing Bruton's agammaglobulinemia tyrosine kinase phosphorylation. In addition, our in vivo results showed that SGK1 inhibition significantly increased the secretion of proinflammatory cytokines, including IL-1ß, IL-6, and TNF-α, and the infiltration of T helper 17 cells in an imiquimod-induced psoriasis mouse model. Altogether, these results show that SGK1 plays a critical role in the pathogenesis of psoriasis by modulating inflammatory responses in skin lesions, indicating that SGK1‒Bruton's agammaglobulinemia tyrosine kinase signaling could be a novel therapeutic target for the control of psoriasis.

Diagnostic Value of Dual-Energy CT Virtual Non-Calcium and Rho/Z Images for Bone Marrow Infiltration in Primary Malignant Bone Tumors.

RATIONALE AND OBJECTIVES: We investigated the diagnostic performance of dual-energy CT (DECT) virtual non-calcium (VNCa) and Rho/Z images for bone marrow infiltration of primary malignant bone tumors (PMBTs). MATERIALS AND METHODS: We retrospectively analyzed 65 patients with PMBT who underwent DECT and MRI within 2 weeks. DECT was used to evaluate the presence and extent of marrow involvement surrounding PMBTs using the SCT, VNCa, and Rho/Z images. MRI was used as the reference standard for measurements. CT values of normal and involved bone marrow areas were measured on VNCa images, and Zeff values were measured on Rho/Z images. The statistical methods used were the 2*C chi-square test, ANOVA test, paired samples t test, and diagnostic performance of the different variables were evaluated using receiver operating characteristic curves. RESULTS: VNCa and Rho/Z images showed higher accuracy (91%, 92% vs. 67%) and sensitivity (90%, 92% vs. 69%) than SCT images for diagnosing bone marrow infiltration in patients with PMBT. The maximum longitudinal diameter of tumor involvement measurements was statistically different between VNCa and SCT, Rho/Z and SCT, MRI, and SCT (all p < 0.05, p = 0.047, p = 0.049, and p = 0.023, respectively). The maximum transverse diameter was statistically significant between SCT and MRI, VNCa and MRI, Rho/Z and MRI (all p < 0.05, and p = 0.015, and p = 0.044, and p = 0.047, respectively). The HU or Zeff values based on the area of interest of VNCa and Rho/Z images differed significantly between the normal and infiltrated bone marrow area (p < 0.001). Receiver operating characteristic curve analysis revealed area under the curves of 0.995 and 0.988, respectively, with cut-off values of -31.57 HU and 7.8, and the sensitivity of both was 96.9%. CONCLUSION: DECT-VNCa and Rho/Z images have good diagnostic value when evaluating bone marrow infiltration in PMBTs.

Recognizing skin conditions in patients with cirrhosis: a narrative review.

Background: The skin is a major target organ for extrahepatic manifestations of liver diseases, and dermatologic abnormalities are common in patients with hepatic disorders. Clinical examination of the skin, nails and hair can allow for appropriate recognition, early diagnosis and treatment of liver diseases, and improvement in the quality of life and life expectancy of affected patients.Methods: We searched 3 databases (Pubmed,Medline and Embase) and selected studies about cirrhosis related skin manifestations and their pathophysiology.Results: A total of 73 articles were included in the review. Studies displayed the spectrum of cutaneous manifestations related to hormonal and vascular changes as well as nail and hair changes in patients with cirrhosis and/or portal hypertension.Conclusion: Cutaneous alterations are important clues or potential indications in the diagnosis of liver cirrhosis. Familiarity with skin conditions can be promptly diagnosed and appropriate management initiated.KEY MESSAGESManifestations of the liver and skin disorders are interrelated in various ways. Cutaneous changes may be the first clue that a patient has liver disease.The skin is a major target organ for extrahepatic manifestations of liver diseases. A broad range of cutaneous alterations can be present in patients with cirrhosis, such as vascular, nail, hair, hormonal changes, etc.Recognizing these signs is crucial so that potential underlying diseases including liver disease can be promptly diagnosed and appropriate management timely initiated.

Combination of clinical and spectral-CT parameters for predicting lymphovascular and perineural invasion in gastric cancer.

PURPOSE: The purpose of this study was to investigate the utility of combining clinical and spectral computed tomography (CT) parameters for the preoperative evaluation of lymphovascular invasion (LVI) and perineural invasion (PNI) in gastric cancers (GCs). MATERIALS AND METHODS: Patients with gastric adenocarcinoma who underwent spectral-CT examination were retrospectively examined. All diagnoses were confirmed by pathology, and the patients were divided into positive and negative groups based on LVI/PNI occurrence. Clinical characteristics, including demographic information, serum tumor markers, and gastroscopic pathological information, were collected. The effective atomic number (Zeff), iodine concentration (IC), and water concentration were measured in the arterial (AP) and venous phase (VP). Differences between the two groups were searched for using independent sample t-test, Mann-Whitney U test, or chi-square (χ2) test and diagnostic performances of the different variables were evaluated using receiver operating characteristic (ROC) curve. RESULTS: A total of 121 patients (96 men, 25 women; mean age: 59 ± 8.7 [SD] years, range: 36-82 years) with gastric adenocarcinoma were included in the study. The serum level of the tumor marker CA125, as well as Zeff and IC in the LVI/PNI-positive group, were significantly higher than in the negative group, and the histological grade and Borrmann type differed between the two groups (all P < 0.05). The discriminating capability analysis demonstrated that CA125 exhibited a favorable performance, and the VP parameters' diagnostic efficacy was superior to that of the AP parameters. The efficacy of the combination of clinical and spectral-CT parameters was superior to that of individual parameters (all AUC > 0.85). The clinical parameters combined with Zeff and IC in the AP and VP exhibited a high evaluation efficacy (AUC = 0.890 [95% CI: 0.826-0.955]; F1 score = 0.888; accuracy = 84.3% [102/121; 95% CI: 76.7-89.8]; sensitivity = 86.2% [75/87; 95% CI: 76.8-92.4]; specificity = 79.4% [27/34; 95% CI: 61.6-90.1]). CONCLUSIONS: Clinical and spectral-CT parameters exhibit considerable capabilities in the preoperative evaluation of LVI and PNI in GCs. The combination of clinical and spectral-CT parameters effectively predicts LVI and PNI in GCs.

CT, MRI, and radiomics studies of liver metastasis histopathological growth patterns: an up-to-date review.

The histopathological growth patterns (HGPs) of liver metastases (LMs) are independently associated with the long-term prognosis of the primary tumor, with different HGPs predicting different patient outcomes and clinical treatment decisions. Non-invasive imaging biomarkers for stratification of HGPs are beneficial for treatment monitoring, evaluation of efficacy, and prognosis prediction of LMs. This review describes the state of research regarding computed tomography (CT), magnetic resonance imaging (MRI), and radiomics imaging biomarkers for LM-HGPs; discusses the advantages of CT, MRI, and radiomics for classification of LM-HGPs; and provides a reference for the stratification of LM-HGPs. Finally, the difficulties and deficiencies of CT, MRI, and radiomics in LM-HGP research are summarized along with the proposed directions for future research.

Vanishing Point Detection Method Based on Constrained Classification for Checkpoints on Urban Roads.

To solve the problems of computational complexity and inaccuracy in classical vanishing point detection algorithms, such as the cascaded Hough transform, a vanishing point detection method based on constrained classification is proposed. First, the short line data are filtered to avoid interference in straight line detection, and then, the line segment is screened and classified by hierarchical clustering according to the image characteristics of the line segment and the variation pattern of angle similarity. Subsequently, Three types of straight line segments with the most significant angle differences are acquired. To prevent the optimization algorithm from getting stuck in the "wrong" local optimum neighborhood or failing to locate the global optimum, a set of constraints are set to further restrict the search. Afterward, the classified line segments are projected into a finite rhombic space, which are then quantified. The point with the maximum vote is eventually identified as the vanishing point. Experimental results show that the proposed method not only greatly reduces the computational complexity of vanishing points but also largely improves the accuracy of vanishing point detection.

The Levels of Wnt5a and Its Receptors Frizzled5 and Frizzled2 as Immunohistochemical Biomarkers of Severity of Psoriasis.

PURPOSE: Psoriasis is a systemic, chronic and inflammatory condition. The exact pathogenesis is unclear. The abnormal expression of Wnt5a pathway in psoriasis vulgaris has been confirmed. Whether it is related to the severity of psoriasis is unclear. METHODS: Thirty-eight skin lesions from psoriasis vulgaris patients and 22 healthy adult skin tissues were taken. The semi-quantitative immunohistochemistry score of Wnt5a, Frizzled5 and Frizzled2 was evaluated under a microscope by two independent dermatologists. Psoriasis area and severity index (PASI) score system was used to evaluate the disease severity. RESULTS: The average PASI score of the patients was 16.25 ± 7.8, and the average duration of disease was 19.6 ± 10.4 months. Wnt5a, Frizzled5 and Frizzled2 were highly expressed in psoriasis lesions. The semi-quantitative immunohistochemistry scores of Wnt5a, Frizzled5 and Frizzled2 were positively correlated with PASI scores (r = 0.71, r = 0.46, r = 0.65, respectively, all P-value < 0.01), but not correlated with duration of disease (r = 0.11, r = 0.17, r = 0.29, respectively, all P-value > 0.05). There were significant positive correlations between Wnt5a and Frizzled5 (r = 0.57, P-value < 0.01), as well as Wnt5a and Frizzled2 (r = 0.59, P-value < 0.01). CONCLUSION: Wnt5a and its receptors play an important role in pathogenesis of psoriasis vulgaris and are positively correlated with the severity of psoriasis, and may be one of the immunohistochemical predictors of the severity of the disease.

The pathological role of Wnt5a in psoriasis and psoriatic arthritis.

Psoriasis (PsO) is a chronic inflammatory skin disease with both local and systemic components. PsO-associated arthritis, known as psoriatic arthritis (PsA), develops in approximately 13%-25% of PsO patients. Various factors associated with both PsO and PsA indicate that these conditions are part of a single disease. Identification of novel targets for the development of drugs to treat both PsO and PsA is desirable to provide more patient-friendly treatment regimens. Such targets will likely represent 'common checkpoints' of inflammation, for example key components or transduction cascades of the signalling pathways involved. Emerging evidence supports involvement of the non-canonical Wnt signalling pathways in the development of both PsO and PsA, especially the Wnt5a-activated signalling cascades. These, together with interlinked factors, are crucial in the interactions among keratinocytes, immune cells and inflammatory factors in PsO, as well as among chondrocytes, osteoblasts and osteoclasts that trigger both subchondral bone remodelling and cartilage catabolism in PsA. This review focuses on the pathological role of Wnt5a signalling and its interaction with other interlinked pathways in both PsO and PsA, and also on the main challenges for future research, particularly with respect to molecules targeting Wnt signalling pathways for the treatment of PsO and PsA.

Identification of Gli1-interacting proteins during simvastatin-stimulated osteogenic differentiation of bone marrow mesenchymal stem cells.

Simvastatin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Our study aimed to illuminate the underlying mechanism, with a specific focus on the role of Hedgehog signaling in this process. BMSCs cultured with or without 10-7 mol/L simvastatin were subjected to evaluation of osteogenic differentiation capacity. Osteogenic markers such as type 1 collagen (COL1) and osteocalcin (OCN), as well as key molecules of Hedgehog signaling molecules, were examined by Western blot and real-time polymerase chain reaction (PCR). Co-immunoprecipitation and mass spectrometry assays were applied to screen for Gli1-interacting proteins. Cyclopamine (Cpn) was used as a Hedgehog signaling inhibitor. Our results indicated that simvastatin increased alkaline phosphatase (ALP) activity; mineralization of extracellular matrix; mRNA expression of ALP, COL1, and OCN; and expression and nuclear translocation of Gli1. Contrasting effects were observed in Cpn-exposed groups, but were partially rescued by the simvastatin treatment. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that Gli1-interacting proteins were primarily associated with mitogen-activated protein kinase (MAPK) (P = 7.04E-04 ), hippo, insulin, and glucagon signaling. Further, hub genes identified by protein-protein interaction network analysis included Gli1-interacting proteins such as Ppp2r1a, Rac1, Etf1, and XPO1/CRM1. In summary, the current study showed that the mechanism by which simvastatin stimulates osteogenic differentiation of BMSCs involves activation of Hedgehog signaling, as indicated by interactions with Gli1 and, most notably, the MAPK signaling pathway.

The first case report of kerion-type scalp mycosis caused by Aspergillus protuberus.

BACKGROUND: Scalp mycosis is often caused by dermatophytes and was so called tinea capitis. There is no published report caused by Aspergillus protuberus. We report a rare case of kerion-type scalp mycosis caused by A. protuberus. CASE PRESENTATION: A 5-year-old girl developed pyogenic mass with pain for 8 days and got a fever for 2 days prior to admission. Surgical incision and drainage of the mass, intravenous cefuroxime and metronidazole in the local hospital aggravated the skin lesions. Species identification was performed by observation of morphologic and biochemical characteristicsand sequencing of the internal transcribed spacer (ITS) and ß-tubulin (BT2). Treatment with oral and topical antifungal agents was effective with no relapse during the six months of clinical follow-up. CONCLUSIONS: Aspergillusis a opportunistic pathogenic fungus and its infection occurs mostly in patients with underlying conditions and immunocompromised statuses. So far no report of kerion-type scalp infection has been reported. The first case of kerion-type scalp mycosis caused by A. protuberus was described to highlight the importance of mycological examination that helps to recognize rare pathogenic fungi. Any boggy lesion with hair loss over the scalp and non-responsive to antibiotics should be suspected as resulting from fungal infection, and mycological examination should be performed, especially in children.

Yes-associated protein promotes the abnormal proliferation of psoriatic keratinocytes via an amphiregulin dependent pathway.

Psoriasis is a chronic inflammatory skin disease with high morbidity, poor treatment methods and high rates of relapse. Keratinocyte hyperproliferation and shortened cell cycles are important pathophysiological features of psoriasis. As a known oncogene, Yes-associated protein (YAP) plays a role in promoting cell proliferation and inhibiting cell apoptosis; however, whether YAP is involved in the pathogenesis of psoriasis remains to be determined. Amphiregulin (AREG), a transcriptional target of YAP, was found to be upregulated in psoriasis, and overexpression of AREG promoted keratinocyte proliferation. In the present study, immunohistochemistry showed that YAP expression was elevated in the skin of psoriasis patients and in the Imiquimod (IMQ) mouse model of psoriasis. Knockdown of YAP in HaCaT cells inhibited cell proliferation, caused cell cycle arrest in G0/G1 phase and promoted apoptosis. These changes in YAP-knockdown HaCaT cells were related to changes in AREG expression. We concluded that YAP may play an important role in the regulation of abnormal keratinocyte proliferation via an AREG-dependent pathway and that YAP could be a new target in the treatment of psoriasis.

Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin.

BACKGROUND: Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin. OBJECTIVE: To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin. METHODS: Following topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter. RESULTS: Our results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration. CONCLUSIONS: Our results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin.

Antimicrobial peptide LL-37 promotes YB-1 expression, and the viability, migration and invasion of malignant melanoma cells.

The cathelicidin antimicrobial peptide, LL-37, is a multifunctional peptide with a broad spectrum of antimicrobial activities, such as chemotaxis and neutralizing endotoxins. Previous studies have demonstrated that it LL­37 serves a functional role in the development of numerous types of cancer including ovarian, breast, prostate and lung cancer. However, its role in the development of malignant melanoma (MM) remains unclear. To determine the role of LL­37 and the potential interaction with Y-box binding protein 1 (YB­1) in MM, RNA interference, western blot, reverse transcription-quantitative polymerase chain reaction, MTT and Transwell assays were performed. The current study demonstrated that LL­37 induced YB­1 expression, and increased tumor cell proliferation, migration and invasion of A375 and A875 MM cell lines. In addition, inhibition of nuclear factor­κB (NF­κB) attenuated LL­37­induced YB­1 expression. These results demonstrate that, through the upregulation of YB­1 expression and the activation of the NF­κB signaling pathway, LL­37 may promote the malignant progression of MM cells in vitro.

Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1.

BACKGROUND/AIMS: Psoriasis is one of the most common inflammatory skin disorders, affecting 3% of the general population. Terminalia chebulanin (TC) is a polyphenolic compound that possesses antioxidant and anti-inflammatory activities. The current study was designed to investigate the effect of TC on psoriatic lesions. METHODS: We examined the protective effect of TC against psoriatic lesions in mice and keratinocyte proliferation in HaCaT cells. RESULTS: We found that TC exhibited potent anti-psoriatic activities, as evidenced by improvement of erythema and scaling scores, decrease of epidermal, ear and skinfold thickening, decrease of tumor necrosis factor α (TNFα), interleukin (IL)-17A, IL-23 and matrix metalloproteinase (MMP)-9 expression, and decrease of TBARS content and increase of GSH content in IMQ-treated mice, and decrease of keratinocyte proliferation, TNFα, IL-17A and IL-23 expression, and ROS level in M5-treated cells. All those effects induced by TC were inhibited by zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase (HO)-1, indicating that HO-1 was responsible the anti-psoriatic effect of TC. Moreover, TC inhibited the upregulation of p65 NF-x03BA;B under in vitro psoriatic condition. ZnPP suppressed TC-induced inhibition of p65 NF-x03BA;B expression. Overexpression of p65 NF-x03BA;B significantly suppressed TC-induced decrease of TNFα, IL-17A and IL-23 expression and keratinocyte proliferation, indicating that HO-1-mediated downregulation of NF-x03BA;B was involved in the anti-psoriatic effect of TC. CONCLUSIONS: The data demonstrate that TC may serve as a potential therapeutic option for psoriatic patients.

Amentoflavone protects against psoriasis-like skin lesion through suppression of NF-κB-mediated inflammation and keratinocyte proliferation.

Psoriasis is a one of the most common chronic skin diseases, which affects 0.6-4.8% of the general population. Amentoflavone (AMF) belongs to the biflavonoid class of flavonoids, possessing various biological effects, such as anti-inflammatory, antioxidant, and anti-apoptotic effects. In the present study, we aimed to investigate the effect of AMF on psoriasis in imiquimod (IMQ) psoriasis-like lesions in mice and keratinocyte proliferation in HaCaT cells. We showed that AMF reduced skinfold thickening, and improved erythema and scaling scores and histological lesions in IMQ-treated mice. AMF exerted potent anti-inflammatory effect via influencing a variety of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-17A, IL-22, and IL-23 in local skin lesions and the whole body. In M5 (a cocktail of cytokines)-treated HaCaT cells, AMF significantly inhibited cell proliferation, promoted apoptosis, and inhibited the increase of expression of cyclin D1, cyclin E, IL-17A, and IL-22. In addition, AMF inhibited the upregulation of p65 NF-κB under psoriatic condition. Moreover, overexpression of p65 NF-κB significantly suppressed the effect of AMF on keratinocyte proliferation, apoptosis, and expression of cyclin D1, cyclin E, IL-17A, and IL-22. These results demonstrated that suppression of NF-κB was involved in AMF-resulted anti-proliferative, apoptosis-promoting, anti-inflammatory effects in keratinocytes. The data demonstrate that AMF may serve as potential therapeutic option for patients with psoriasis.