Anti-DNA antibody-targeted D-peptide nanoparticles ameliorate lupus nephritis in MRL/lpr mice.

Peptide ALW (ALWPPNLHAWVP) targeting anti-dsDNA antibodies has shown promising therapeutic effects in alleviating lupus nephritis, but is potentially limited by poor stability and non-kidney targeting. We recently developed a D-form modified ALW, called D-ALW, which has the capacity to widely inhibit pathogenic polyclonal anti-dsDNA antibody reactions. Further modification of D-ALW using PEG-PLGA nanoparticles to enhance good kidney-targeting ability and extend half-life. Here, we demonstrate that the D-form modified ALW maintains higher binding and inhibition efficiencies and achieves higher stability. Most importantly, D-ALW nanoparticles exhibit excellent kidney-targeting ability and prolong the half-life of the peptides in BALB/c mice. Additionally, compared to D-ALW, D-ALW nanoparticles significantly reduce the glomerular deposition of IgG and C3, improve renal histopathologies, such as glomerular proliferation and inflammatory cells infiltration, and markedly prolong lifespan in MRL/lpr lupus-prone mice. Overall, these results establish that the D-ALW nanoparticles offer synergistic benefits in both safety and efficacy, providing long-term renal preservation and treatment advantages in lupus nephritis.

Genetic association between asthma and alopecia areata: A two-sample Mendelian randomization study.

BACKGROUND: Many patients with asthma experience alopecia areata (AA) in their lives. However, it is unclear whether asthma causes or results from AA. Our objective was to investigate the genetic causal relationship between asthma and AA. METHODS: Two-sample Mendelian randomization (MR) was used to assess the causal relationship between asthma and AA based on the largest publicly available genome-wide association study summary statistics. Androgenetic alopecia (AGA) and cicatricial alopecia (CA) were chosen as the control groups for AA. The main estimates were obtained using inverse variance weighting meta-analysis (IVW), Mendelian randomization-Egger (MR-Egger), maximum likelihood estimation, and the weighted median. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger, and leave-one-out methods. Lastly, we conducted a reverse MR analysis to evaluate the possibility of reverse causation. RESULTS: Genetically, asthma is associated with an increased risk of AA, while the association between genetically predicted AGA or CA and asthma was negative. The risk of AA increased by 1.86 times in patients with asthma under the IVW method (OR = 1.86, 95% CI = 1.31-2.629, p < 0.001). The reverse MR analysis did not find evidence supporting reverse causality from three phenotypes of alopecia to asthma. Sensitivity analyses yielded consistent causal estimates. CONCLUSION: This study suggests that asthma is causally associated with AA. The findings deepen our understanding of the role of asthma in the pathology of AA, which emphasizes the potential for opening a new vista for the prevention and diagnosis of AA.

First report of anthracnose of Lithocarpus polystachyus caused by Colletotrichum fructicola in China.

Lithocarpus polystachyus (Wall. ex A. DC.), an economically valuable plant species belonging to the Fagaceae family, has been used as herbal tea to prevent diabetes because of the high content of flavonoids and dihydrochalcones in the leaves (Shang et al. 2022). In July 2022, the severe leaf lesion on L. polystachyus was first observed in Yongshun County, Xiangxi autonomous prefecture (28°45'34''N, 109°40'11''E), Hunan province, China. Yongshun County is characterized by hills and mountains, situated in a subtropical region with a mild and humid climate. A second outbreak in July 2023 was observed in the same area. The observed incident rates in the past two years were 87.3% and 90.6%, respectively. Once infected, almost all plant leaves will be infected, leading to a substantial reduction in the yield of L. polystachyus. The disease presented symptoms characterized by round or irregularly shaped lesions that initially manifested as brown spots. These lesions frequently merged into larger, dark-brown areas along the leaf margins before eventually wilting. To ascertain the pathogenic species responsible for this disease, fungal isolation was conducted using a tissue separation method (Xu et al. 2023). The infected leaf tissues were surface-disinfected with 75% ethanol and 0.1% HgCl then small pieces (1×1 cm), were placed onto potato dextrose agar (PDA) medium (Sigma-Aldrich, 70139) and incubated at 28°C for 6-9 days. Colonies were villiform and initially white, becoming gray after 6 days. Sterilized dissecting needles were used to pick single hyphal tips from the edge of the colonies and placed onto PDA for strain purification. After 15 days, the purified colonies grew fluffy white hyphae with abundant conidia. The conidia were cylindrical, had round ends, and ranged from 5.75 to 14.83 µm long and 1.75 to 2.38 µm wide (n=50). According to morphological and cultural characteristics, these isolates were preliminarily identified as Colletotrichum fructicola Prihast., L. Cai & K.D. Hyde (Damm et al. 2012). To further affirm the identity of the pathogen, DNA was extracted from mycelia using a DNA extraction kit (Sigma-Aldrich, G2N70). The internal transcribed spacer (ITS) region, the transcription elongation factor (TEF), and the actin (ACT) gene were then amplified from genomic DNA extracted from three isolates (Cof1, Cof2, and Cof3) using specific primers. The primers utilized were ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R and ACT-512F/ACT-783R (Carbone and Kohn 1999) for ITS region, transcription elongation factor gene and actin gene amplification, respectively. Sequence identity indicated that these isolates were highly homologous to C. fructicola. The ITS (Genbank No. PP002156, OR880553 and OR880554), TEF (No. PP061421, PP061422 and PP061423), and ACT (No. PP061418, PP061419 and PP061420) sequences of the isolates Cof1, Cof2, and Cof3 shared 99 to 100% identity with their counterparts (No. OR083309, MF627961, and OQ427895) in C. fructicola, respectively. A neighbor-joining phylogenetic tree constructed using MEGA11 (Tamura et al. 2021) also indicated that these isolates were C. fructicola. Both morphological and molecular characteristics confirmed the identification of this pathogen as C. fructicola. Colletotrichum species are known to cause anthracnose disease in a variety of economically important crops (Sharma and Kulshrestha 2015). To further validate the ability of the isolated C. fructicola to induce the same symptoms as observed in the field, the pathogenicity assay was assessed following Koch's postulates (Gradmann, 2014). Conidial suspensions (1×105 conidia per mL) from three isolates were individually inoculated onto artificially wounded leaves of 3-year-old L. polystachyus. Negative controls were established by inoculating leaf wounds with sterile distilled water. The plants were incubated in a greenhouse at 28°C and 90% humidity with a 12-h photoperiod. The experiment was replicated three times. Necrotic lesions were observed on all pathogen-inoculated wounds within 6 days after inoculation, whereas controls showed no observable symptoms. Morphological and molecular characterization of re-isolated pathogens from infected leaves indicated that the pathogens were identical. To our knowledge, this is the first report of anthracnose of L. polystachyus caused by C. fructicola in China. Farmers in the local mountainous areas are economically reliant on L. polystachyus production, while anthracnose has caused over half of the trees to lose their commercial value, resulting in significant economic losses. Our findings hold great promise for advancing strategies in the prevention and treatment of anthracnose in L. polystachyus.

Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells.

Anti-double-stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti-dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti-dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti-dsDNA IgG. The results revealed that TWEAK dose-dependently enhanced cellular internalization of anti-dsDNA IgG and the expression of high-mobility group box 1 (HMGB1). In addition, TWEAK and anti-dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti-dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor-κB and phosphatidylinositide 3-kinase/protein kinase B pathways. Therefore, TWEAK/Fn14 signaling contributes to the penetration of anti-dsDNA IgG and relevant fibrotic processes in mesangial cells.

BP180 dysfunction triggers spontaneous skin inflammation in mice.

BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed ΔNC16A) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.

ER-to-Golgi blockade of nascent desmosomal cadherins in SERCA2-inhibited keratinocytes: Implications for Darier's disease.

Darier's disease (DD) is an autosomal dominantly inherited skin disorder caused by mutations in sarco/endoplasmic reticulum Ca2+ -ATPase 2 (SERCA2), a Ca2+ pump that transports Ca2+ from the cytosol to the endoplasmic reticulum (ER). Loss of desmosomes and keratinocyte cohesion is a characteristic feature of DD. Desmosomal cadherins (DC) are Ca2+ -dependent transmembrane adhesion proteins of desmosomes, which are mislocalized in the lesional but not perilesional skin of DD. We show here that inhibition of SERCA2 by 2 distinct inhibitors results in accumulation of DC precursors in keratinocytes, indicating ER-to-Golgi transport of nascent DC is blocked. Partial loss of SERCA2 by siRNA has no such effect, implicating that haploinsufficiency is not sufficient to affect nascent DC maturation. However, a synergistic effect is revealed between SERCA2 siRNA and an ineffective dose of SERCA2 inhibitor, and between an agonist of the ER Ca2+ release channel and SERCA2 inhibitor. These results suggest that reduction of ER Ca2+ below a critical level causes ER retention of nascent DC. Moreover, colocalization of DC with ER calnexin is detected in SERCA2-inhibited keratinocytes and DD epidermis. Collectively, our data demonstrate that loss of SERCA2 impairs ER-to-Golgi transport of nascent DC, which may contribute to DD pathogenesis.

A unified mitochondria mechanistic target of rapamycin acyl-coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells.

Metformin exhibits antiproliferative and proapoptotic effects in a variety of diseases, characterized by malignant and nonmalignant hyperplastic cells; however, the underlying molecular mechanism of metformin in psoriasis has not been elucidated. In the current study, we found that after metformin treatment the proliferation of human immortalized keratinocytes (HaCaT) was significantly inhibited, while cell apoptosis was increased in a dose-dependent manner, accompanied with enhanced protein expression of acyl-coenzyme A dehydrogenase 10 (ACAD10). Furthermore, mechanism analysis revealed that ACAD10 expression is induced by downregulated activities of mechanistic target of rapamycin 1 (mTORC1) signaling rather than AMP-activated protein kinase signaling. The inactivation of mTORC1 by rapamycin pretreatment or rotenone-induced mitochondrial complex inhibition showed a similar effect because of the metformin treatment on the proliferation and apoptosis of HaCaT keratinocytes. Overexpression of mTORC1 almost reversed the antiproliferation and proapoptosis effects induced by metformin. This study showed that the metformin treatment inhibited HaCaT cells proliferation and promoted apoptosis by affecting the mitochondrial-mTORC1 signaling and elevated the ACAD10 expression. Hence, metformin can be used as a potential therapeutic agent for psoriasis.

MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/ß-catenin pathway.

MicroRNAs (miRNAs) participate in the development and progression of melanoma. However, while dysregulation of microRNA-378 (miR-378) has been seen in various cancer types, its clinical importance and function in melanoma are poorly elucidated. In this work, miR-378 expression in melanoma and in adjacent non-cancerous tissue was evaluated with a quantitative real-time polymerase chain reaction. A series of assays (wound healing, Transwell, and nude mouse subcutaneous tumor model) were used to investigate the implications of abnormal miR-378 regulation on melanoma cell migration and invasion in vitro, and on tumorigenicity in vivo. Prediction and conformation of the miR-378 target gene was undertaken using bioinformatic analysis and luciferase reporter system. Expression of miR-378 was often increased in melanoma, and shown to potentiate its migration, invasion, and tumorigenicity. miR-378 acted, at least partially, through inhibition of the potential target FOXN3 and via Wnt/ß-catenin pathway activation. The findings indicate that miR-378 triggers melanoma development and progression. This miRNA could be a novel diagnostic and prognostic biological marker and provide utility for targeted treatment of melanoma.

Tumor Necrosis Factor (TNF) Receptor Expression Determines Keratinocyte Fate upon Stimulation with TNF-Like Weak Inducer of Apoptosis.

The interaction between tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) regulates the fate of keratinocytes, depending on the relative expression of TNF receptor (TNFR) 1 or TNFR2. However, the precise mechanism underlying this TWEAK-mediated regulation remains unclear. The aim of this study was to provide comprehensive insight into the roles of Fn14, TNFR1/2, and other relevant molecules in the fate of keratinocytes. Further, we sought to elucidate the structural basis for the interaction of TWEAK and Fn14 in regulating cellular outcomes. Normal keratinocytes (mainly expressing TNFR1) and TNFR2-overexpressing keratinocytes were stimulated with TWEAK. Through immunoprecipitation and Western blotting of keratinocyte lysates, we elucidated the associations between Fn14, TNFR-associated factor 2 (TRAF2), cellular inhibitor of apoptosis protein 1 (cIAP1), and TNFR1/2 molecules. Additionally, we found that TRAF2 exhibited binding to Fn14, cIAP1, and TNFR1/2. Our data suggest that TWEAK induces apoptosis in normal keratinocytes and proliferation in TNFR2-overexpressing keratinocytes in a TNF-α-independent manner; however, inhibition of TRAF2 appears to reverse this effect. Interestingly, the interaction between TWEAK and Fn14 increased TNFR1-associated death domain protein and caspase-8 expression in normal keratinocytes and promoted cytoplasmic import of cIAP1 in TNFR2-overexpressing keratinocytes. In conclusion, we found that the Fn14-TRAF2-TNFR signaling axis mediates TWEAK's regulation of the fate of keratinocytes, possibly in a manner involving the TNF-α-independent TNFR signal transduction.

[Design of Multifunctional Automated External Defibrillator Based on STM32].

This paper presents a design of multifunctional portable automated external defibrillator based on STM32F103VC SCM. The defibrillator mainly realizes the defibrillation and ECG analysis function, and according to the clinical actual need, increases information storage and transmission function, query of local records, the function of synchronous LCD display and voice prompt in the defibrillation process. The device uses the defibrillating electrodes to measure body resistance, ECG and so on. We detailedly researched and achieved the discharge module of biphasic defibrillation apparatus based on the damping of two order discharge circuit, and finished the real-time LCD display and voice prompt modules of defibrillation information based on the control of PIC24FJ256DA210 chip.

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling.

Tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) engages its sole receptor, fibroblast growth factor-inducible 14 (Fn14), which participates in various inflammatory and immunologic processes. TWEAK/Fn14 interaction induces different cell fates depending on the local microenvironment, which correlates with certain expression profiles of TNF receptors (TNFR). The predominant expression of TNFR1 or TNFR2 facilitates cell death or proliferation, respectively, on TWEAK/Fn14 activation. TNFR-associated factors (TRAF) interact with Fn14, cellular inhibitor of apoptosis protein (cIAP)-1, and TNFR, consequently transducing signals from TWEAK to downstream cytokines and cell cycle mediators. An Fn14-TRAF2-TNFR axis has been suggested in the function of TWEAK/Fn14 signaling, which may serve as a target in the development of novel therapeutic strategies for many diseases that have Fn14-overexpressing cells in affected tissues. The aims of this review are: 1) to present the main results on TWEAK/Fn14 regulation of cell fates, 2) to analyze the mechanism of the Fn14-TRAF2-TNFR axis, and 3) to summarize the potential strategies in the pharmacologic targeting of this axis.

microRNA-216b inhibits cell proliferation and migration in human melanoma by targeting FOXM1 in vitro and in vivo.

MicroRNAs (miRNAs) play an increasingly important role in cancer growth by coordinately suppressing genes that control cell migration, proliferation, and invasion. The above results can be achieved through the regulation of gene expression by miRNAs by suppressing translation or the direct sequence-specific degradation of the targeted mRNA. In the present study, we indicate that the expression of miR-216b could be effectively repressed both in human melanoma tissues through a comparison with primary melanoma and in human melanoma cell lines through a comparison with a normal human keratinocyte line. Moreover, miR-216b induced a clear decrease in melanoma cell proliferation and migration in vitro. Forkhead box M1 (FOXM1) was confirmed as a target gene of miR-216b, and the overexpression of miR-216b markedly repressed the luciferase activity of reporter plasmids containing the FOXM1 3'-UTR (untranslated region). Furthermore, miR-216b suppressed melanoma cell growth in nude mice in vivo, with the effects of miR-216b overexpression on melanoma cell growth and proliferation reversed by FOXM1 overexpression. The results demonstrated that miR-216b is a tumor suppressor in melanoma, identified the FOXM1 signaling pathway as a target of miR-216b action, and suggested a potential therapeutic role for miR-216b in melanoma.

TWEAK/Fn14 Activation Participates in Skin Inflammation.

Tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) participates in multiple biological activities via binding to its sole receptor-fibroblast growth factor-inducible 14 (Fn14). The TWEAK/Fn14 signaling pathway is activated in skin inflammation and modulates the inflammatory responses of keratinocytes by activating nuclear factor-κB signals and enhancing the production of several cytokines, including interleukins, monocyte chemotactic protein-1, RANTES (regulated on activation, normal T cell expressed and secreted), and interferon gamma-induced protein 10. Mild or transient TWEAK/Fn14 activation contributes to tissular repair and regeneration while excessive or persistent TWEAK/Fn14 signals may lead to severe inflammatory infiltration and tissue damage. TWEAK also regulates cell fate of keratinocytes, involving the function of Fn14-TNF receptor-associated factor-TNF receptor axis. By recruiting inflammatory cells, promoting cytokine production, and regulating cell fate, TWEAK/Fn14 activation plays a pivotal role in the pathogenesis of various skin disorders, such as psoriasis, atopic dermatitis, cutaneous vasculitis, human papillomavirus infection and related skin tumors, and cutaneous autoimmune diseases. Therefore, the TWEAK/Fn14 pathway may be a potential target for the development of novel therapeutics for skin inflammatory diseases.

2940-nm Er:YAG fractional laser enhanced the effect of topical drug for psoriasis.

We observed the promoting effects of the 2940-nm erbium:YAG (Er:YAG) fractional laser in topical drug delivery for psoriasis. A total of five (four males and one female) recalcitrant psoriasis patients were given laser treatment eight times at 1-week intervals with the following parameters: 5-11% spot density and 100-µm energy depth. The psoriatic skin lesions on the left knee and the corresponding lesions at the right ones of each psoriasis patient were randomly divided into two groups: laser + topical drug group (L) and drug alone group (D). The psoriatic lesions in both groups were treated with the same topical treatment (calcipotriol ointment). The corresponding psoriatic lesions in the L group received extra 2940-nm Er:YAG laser irradiation before topical treatment. The photos of psoriatic lesions were taken before each treatment. The final photos were obtained from the patients at the seventh day after the final treatment. Drug alone or in combination with laser Er:YAG both reduced psoriatic lesions. However, with the increase in the number of treatments, increasing differences were observed between the treatment and the control sides. The therapeutic outcomes in the L groups were better than those in the D groups. Psoriasis area and severity index (PASI) scores for five cases of both groups were decreased. However, the scores in the L groups were lower than those in the D groups. The use of 2940 nm Er:YAG promoted the absorption of topical drugs for psoriasis, improving the therapeutic effect.

[Research and Design of a System for Detecting Automated External Defbrillator Performance Parameters].

OBJECTIVES: In order to regularly detect the performance parameters of automated external defibrillator (AED), to make sure it is safe before using the instrument, research and design of a system for detecting automated external defibrillator performance parameters. METHODS: According to the research of the characteristics of its performance parameters, combing the STM32's stability and high speed with PWM modulation control, the system produces a variety of ECG normal and abnormal signals through the digital sampling methods. RESULTS: Completed the design of the hardware and software, formed a prototype. CONCLUSIONS: This system can accurate detect automated external defibrillator discharge energy, synchronous defibrillation time, charging time and other key performance parameters.

Dihydroartemisinin suppresses growth of squamous cell carcinoma A431 cells by targeting the Wnt/ß-catenin pathway.

The antimalarial effects of dihydroartemisinin (DHA) have been well documented. However, its potential against skin cancer has not been explored as yet. Therefore, we assessed the function of DHA as an inhibitory factor of squamous cell carcinoma in A431 cells and the underlying mechanism was explored. After stimulation of A431 cells and Hacat cells (normal human keratinocyte cells, as control) with various doses of DHA, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the proliferation of both cell lines and cell apoptosis was analyzed by flow cytometric analysis. Furthermore, after pretreatment with the Wnt/ß-catenin signaling pathway activator BIO or anti-caspase-3 antibody, mRNA levels of antiapoptotic gene survivin and proapoptotic gene caspease-3 were explored by quantitative real-time PCR, the corresponding protein levels were detected by western blotting, and the proliferation of A431 cells was also analyzed. DHA inhibited the proliferation and viability of A431 cells in a time-dependent and dose-dependent manner and induced cell apoptosis. We also observed decreased surviving expression and increased caspase-3 expression of A431 cells. Furthermore, these effects depended on the suppression of Wnt/ß-catenin signaling as pretreatment with the Wnt activator BIO markedly dampened the DHA-induced effects. More interestingly, when the caspase-3 expression was silenced using an antibody, the DHA-induced growth inhibition of A431 cells was offset significantly. Our results confirm that DHA inhibits skin cancer A431 cells by suppressing Wnt/ß-catenin signaling. Our findings provide a potential target for squamous cell carcinoma treatment.

Lipopolysaccharide induces TREM-1-dependent HIF-1α expression in human keratinocyte cell line.

Bacterial infection is an important factor that can trigger and exacerbate psoriasis. The protein triggering receptor expressed on myeloid cells type-1 (TREM-1) is overexpressed in psoriasis and decreased after a successful treatment. Hypoxia inducible factor-1α (HIF-1α), subunit of the transcription factor HIF-1, has participated in angiogenesis and inflammation in psoriasis. Increased expressions of TREM-1 and HIF-1α are associated with the infection of microbial pathogens. However, the association between TREM-1 and HIF-1α still needs to be elucidated. Results of immunofluorescence showed an overexpression of TREM-1 and HIF-1α in HaCaT keratinocytes exposed to 1 µg/mL of lipopolysaccharide (LPS). Particularly, silencing of TREM-1 expression by siRNA suppressed the inducible effect of LPS on phosphoinositide 3-kinase (PI3 K)/Akt, the critical transduction mediator, and HIF-1α. Furthermore, the PI3 K inhibitor wortmannin effectively blocked the increased level of HIF-1α induced by LPS. However, there was no significant change in LPS-induced expression of TREM-1. Expressions of TREM-1, HIF-1α, and phosphorylated Akt proteins were further examined by real-time PCR and Western blot, respectively. Our data suggest that TREM-1 and HIF-1α are expressed on keratinocytes and could be upregulated by bacterial infection. Moreover, LPS-induced TREM-1 has an ability to mediate the expression of HIF-1α in HaCaT cells through the PI3 K/Akt pathway. Our study provides new insights into the possible mechanism of TREM-1 and HIF-1α in psoriasis.

Rasch analysis holds no brief for the use of the Dermatology Life Quality Index (DLQI) in Chinese neurodermatitis patients.

BACKGROUND: The Dermatology Life Quality Index (DLQI) is the most widely used measure of health-related quality of life (HRQoL) associated with skin disease. Recently, the psychometric properties of the DLQI have caused some controversy because the instrument appears not to meet the requirements of modern test theory. The purpose of this study was to assess whether these psychometric issues also occur in Chinese patients with neurodermatitis. METHODS: One hundred fifty consecutive outpatients (83 males and 67 females) seeking treatment for neurodermatitis were assessed for eligibility for this prospective study between July 1, 2011 and September 30, 2011. The DLQI and a demographic questionnaire were completed. One female participant who incompletely answered the DLQI was excluded. Data were analyzed using the Rasch model in order to obtain meaningful scores for the DLQI. Scale assessment included analysis of rating scale function, item fit to the Rasch model, aspects of person-response validity, unidimensionality, person-separation reliability, and differential item function. RESULTS: The rating scale advanced monotonically for all items in the DLQI, but item 9 did not demonstrate acceptable goodness-of-fit (Infit MnSq values >1.3) to the Rasch model. The 10 items of the DLQI met the criteria for person-separation reliability (PSI = 2.38) and the first latent dimension (general QoL) accounted for 50.8 % of the variance; but the variance explained by the second dimension (7.1 %) exceeded the criterion of 5 %. There were also limitations related to person-response validity, because ≥ 5 % (18.1 %) of cases demonstrated unacceptable fit. There was no uniform differential item functioning. CONCLUSIONS: For neurodermatitis patients, the DLQI seems to have poor fit to the Rasch model; therefore, we recommend against using this instrument with neurodermatitis patients.

The long-term effect of 1550 nm erbium:glass fractional laser in acne vulgaris.

We evaluated the short-term and long-term effects of the 1550 nm erbium:glass (Er:glass) fractional laser in the treatment of facial acne vulgaris. Forty-five (9 male and 36 female) acne patients were treated 4 times at 4-week intervals with the following parameters: 169 spot density and 15-30 mJ/cm(2) fluence. There was no control group. The laser spots were adjustable (maximum overlap: 20%) according to the treatment area, and delivered in rows in order to cover all the face. Clinical photographs were taken. The IGA scores and lesion counts were performed for each treatment. Their current state was obtained by phone call follow-up to determine the long-term effect and photographs were offered by themselves or taken in hospital. After four treatments, all patients had an obvious reduction of lesion counts and IGA score and the peak lesion counts decreased to 67.7% after the initial four treatment sessions. For long-term effect, 8 patients lost follow-up, hence 37 patients were followed-up. 8 patients were 2-year follow up, 27 at the 1-year follow-up, and all patients at the half-year follow-up. The mean percent reduction was 72% at the half-year follow-up, 79 at the 1-year follow-up and 75% at the 2-year follow-up. Side effects and complications were limited to transient erythema and edema, and few patients suffered from transient acne flare-ups and sensitivity. All patients responded that their skin was less prone to oiliness. In conclusion, acne can be successfully treated by 1550 nm Er:glass fractional laser, with few side effects and prolonged acne clearing.

Wnt/ß-Catenin and Wnt5a/Ca Pathways Regulate Proliferation and Apoptosis of Keratinocytes in Psoriasis Lesions.

BACKGROUND / AIMS: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro. METHODS: The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC), and ß-catenin were determined, and cell cycle activity, proliferation and apoptosis were assessed. RESULTS: The expression of WNT5A, FZD2 and FZD5 mRNA and protein were increased in psoriatic lesions. Wnt5a knockdown suppressed proliferation and induced apoptosis in HaCaT and NHK cells. Additionally, expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting analyses demonstrated reduction in ß-catenin and PKC protein levels. CONCLUSION: Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/ß-catenin or Wnt5a/Ca(2+) pathways.