LSD1 interacting with HSP90 promotes skin wound healing by inducing metabolic reprogramming of hair follicle stem cells through the c-MYC/LDHA axis.

It has been demonstrated that hair follicle stem cells (HFSCs) can contribute to wound closure and repair. However, the specific mechanism remains unclear due to the complexity of the wound repair process. Lysine-specific demethylase 1 (LSD1), an important gene for the regulation of stem cell differentiation, has been reported to participate in wound healing regulation. Heat shock protein 90 (HSP90), a chaperone protein, is recently discovered to be a driver gene for wound healing. This study explored the molecular mechanisms by which the binding between LSD1 and HSP90 affects the role of HFSCs during skin wound healing. Following bioinformatics analysis, the key genes acting on HFSCs were identified. The expression of LSD1, HSP90, and c-MYC was found to be upregulated in differentiated HFSCs. Analysis of their binding affinity revealed that LSD1 interacted with HSP90 to enhance the stability of the transcription factor c-MYC. Lactate dehydrogenase A (LDHA) has been documented to be essential for HFSC activation. Therefore, we speculate that LDHA may induce the differentiation of HFSCs through glucose metabolism reprogramming. The results showed that c-MYC activated LDHA activity to promote glycolytic metabolism, proliferation, and differentiation of HFSCs. Finally, in vivo animal experiments further confirmed that LSD1 induced skin wound healing in mice via the HSP90/c-MYC/LDHA axis. From our data, we conclude that LSD1 interacting with HSP90 accelerates skin wound healing by inducing HFSC glycolytic metabolism, proliferation, and differentiation via c-MYC/LDHA axis.

A multicenter, randomized, double-blinded, placebo-controlled, phase â ¢ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

CPR5 positively regulates pattern-triggered immunity via a mediator protein.

Plant cells possess a two-layered immune system consisting of pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), mediated by cell surface pattern-recognition receptors and intracellular nucleotide-binding leucine-rich repeat receptors (NLRs), respectively. The CONSTITUTIVE EXPRESSION OF PR GENES 5 (CPR5) nuclear pore complex protein negatively regulates ETI, including ETI-associated hypersensitive response. Here, we show that CPR5 is essential for the activation of various PTI responses in Arabidopsis, such as resistance to the non-adapted bacterium Pseudomonas syringae pv. tomato DC3000 hrcC- . In a forward-genetic screen for suppressors of cpr5, we identified the mediator protein MED4. Mutation of MED4 in cpr5 greatly restored the defective PTI of cpr5. Our findings reveal that CPR5 plays opposite roles in regulating PTI and ETI, and genetically regulates PTI via MED4.

Development and validation of the psoriasis scale among the system of quality of life instruments for chronic diseases QLICD-PS (V2.0).

BACKGROUND AND PURPOSE: Psoriasis (PS) is difficult to cure with a high incidence. Therefore, the quality of life (QOL) of people with Psoriasis has caused widespread concern. Universal scales respond poorly to subtle changes caused by specific diseases, which makes it challenging to fully understand the impact of QOL in patients with psoriasis. In view of the deficiencies of the universal scale and the lack of a specific scale suitable for Chinese cultural background, this study aims to develop the psoriasis scale among the system of QOL instruments for chronic diseases QLICD-PS (V2.0). METHODS: The scale QLICD-PS (V2.0) was developed based on the procedural decision-making approach and the experience of establishing scales at home and abroad. 122 patients with psoriasis were participated in measuring QOL 3 times before and after treatments. The reliability was assessed by test-retest reliability (Pearson's correlation coefficients) and also internal consistency (Cronbach's alpha coefficients). Qualitative analysis was adopted to evaluate content validity; item-domain correlation analysis, multi-dimensional scaling analysis, and factor analysis were adopted to evaluate the construct validity; the SF-36 scale was used as the criterion to evaluate the criterion-related validity due to lack of gold standard. Paired t tests were performed to evaluate the responsiveness on each domain/facet as well as the total of the scale, with Standardized Response Mean (SRM) being calculated. RESULTS: The QLICD-PS was composed of the general module including 3 domains (28 items) and the psoriasis specific module (13 items). The Cronbach's α of the specific module, the general module and the total scale of the QLICD-PS was 0.78, 0.87 and 0.74 respectively, the split-half reliability of the specific module, the general module and the total scale was 0.81, 0.91 and 0.81, respectively, both indicating high reliability. Correlation and factor analysis confirmed good construct validity and criterion-related validity. After treatments, the score changes in the total scale were statistically significant with SRM being 0.5, showing moderate responsiveness. CONCLUSION: As the first psoriasis-specific QOL scale developed by the modular approach in Chinese, the QLICD-PS showed good reliability, validity and responsiveness, and could be used to measure the QOL of Patients with psoriasis specifically and sufficiently.

A Case of CD5-Positive Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type Secondary to Chronic Lymphedema.

ABSTRACT: Primary cutaneous lymphoma occurring at the site of lymphedema is a rare complication. A total of 13 cases of primary cutaneous lymphoma associated with chronic lymphedema have been reported in international studies. We reported a case of cutaneous diffuse large B-cell lymphoma (DLBCL) (leg type) secondary to chronic lymphedema of the lower limbs. Histopathology showed hyperkeratosis of epidermis, acanthosis, and significant edema in the superficial dermis, with diffuse mononuclear infiltration in the dermis. Immunohistochemical studies revealed the expression of CD5, CD20, Pax-5, Bcl-2, Bcl-6, MUM-1, c-myc, and Ki-67. Therefore, the diagnosis of cutaneous DLBCL (leg type) was made. The study further confirmed the association between lymphoma and lymphedema. Especially, it showed CD5 expression. CD5-positive DLBCLs is a specific subgroup of DLBCLs, only approximately 10% of DLBCLs express CD5.

The protective effects of TGR5 against ultraviolet B irradiation in epidermal stem cells.

Repetitive exposure to ultraviolet radiation (UVR) results in continuous insults to the skin, including continuous loss of the capacities of epidermal stem cells (ESCs). Takeda G-protein-coupled receptor-5 (TGR5) participates in a variety of physiological activities, but its biological function in skin has not been reported. In this study, we report that TGR5 could be detected in ESCs and its expression was reduced after ultraviolet B (UV-B) irradiation. Treatment with the specific TGR5 agonist 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide (GPBARA) prevented UV-B-induced oxidative stress by reducing 4-hydroxy-2-nonenal and increasing the level of glutathione. We also found that the presence of GPBARA improved UV-B irradiation-induced mitochondrial dysfunction by elevating mitochondrial membrane potential. Interestingly, our results indicate that GPBARA pretreatment suppressed UV-B irradiation-induced reduced cell viability, release of lactic dehydrogenase, and secretion of high mobility group box 1. Notably, GPBARA pretreatment inhibited UV-B irradiation-induced decrease in integrin ß1 and Krt19, dependent on TGR5. Mechanistically, we found that the activation of TGR5 by GPBARA increased Wnt1, Wnt3a, Myc, and cyclin D1 in ESCs. Our data suggest a new function of TGR5 in regulating ESCs.

Increasing seed size and quality by manipulating BIG SEEDS1 in legume species.

Plant organs, such as seeds, are primary sources of food for both humans and animals. Seed size is one of the major agronomic traits that have been selected in crop plants during their domestication. Legume seeds are a major source of dietary proteins and oils. Here, we report a conserved role for the BIG SEEDS1 (BS1) gene in the control of seed size and weight in the model legume Medicago truncatula and the grain legume soybean (Glycine max). BS1 encodes a plant-specific transcription regulator and plays a key role in the control of the size of plant organs, including seeds, seed pods, and leaves, through a regulatory module that targets primary cell proliferation. Importantly, down-regulation of BS1 orthologs in soybean by an artificial microRNA significantly increased soybean seed size, weight, and amino acid content. Our results provide a strategy for the increase in yield and seed quality in legumes.

Chromoblastomycosis Caused by Fonsecaea nubica: First Report in Northern China and Literature Review.

Chromoblastomycosis is found worldwide with higher incidence in tropical and subtropical regions. Fonsecaea spp. is one of the major causative agents of this disease. First case of chromoblastomycosis due to Fonsecaea nubica in Northern China is reported in a 75-year-old Chinese male. We firstly summarized molecular identification methods of Fonsecaea spp. and all the strains of F. nubica reported in the literature. Sequencing of internal transcribed spacer alone and/or combined with actin (ACT1), partial cell division cycle (CDC42) and partial beta-tubulin (BT2) were most commonly used to identify species, while lactase (Lac), homogentisate (HmgA) and polyketide synthase (PKS1) were also used in some cases. Most strains were isolated from South America and Eastern China. Five clinical cases of chromoblastomycosis due to F. nubica from Asia and Europe were also reviewed. All the five patients were male, over 30 years old, and their lesions occurred after trauma.

Regulation of compound leaf development in Medicago truncatula by fused compound leaf1, a class M KNOX gene.

Medicago truncatula is a legume species belonging to the inverted repeat lacking clade (IRLC) with trifoliolate compound leaves. However, the regulatory mechanisms underlying development of trifoliolate leaves in legumes remain largely unknown. Here, we report isolation and characterization of fused compound leaf1 (fcl1) mutants of M. truncatula. Phenotypic analysis suggests that FCL1 plays a positive role in boundary separation and proximal-distal axis development of compound leaves. Map-based cloning indicates that FCL1 encodes a class M KNOX protein that harbors the MEINOX domain but lacks the homeodomain. Yeast two-hybrid assays show that FCL1 interacts with a subset of Arabidopsis thaliana BEL1-like proteins with slightly different substrate specificities from the Arabidopsis homolog KNATM-B. Double mutant analyses with M. truncatula single leaflet1 (sgl1) and palmate-like pentafoliata1 (palm1) leaf mutants show that fcl1 is epistatic to palm1 and sgl1 is epistatic to fcl1 in terms of leaf complexity and that SGL1 and FCL1 act additively and are required for petiole development. Previous studies have shown that the canonical KNOX proteins are not involved in compound leaf development in IRLC legumes. The identification of FCL1 supports the role of a truncated KNOX protein in compound leaf development in M. truncatula.

Combination treatment of oral terbinafine with topical terbinafine and 10% urea ointment in hyperkeratotic type tinea pedis.

Hyperkeratotic-type tinea pedis is chronic and recalcitrant to topical antifungal agents. Some topical antifungal agents are effective; however, long duration of therapy is required, which often reduce the treatment compliance of patients. To seek for short period therapy of hyperkeratotic type tinea pedis, in this study, we observed the efficacy and safety of treatment of topical terbinafine and 10% urea ointment combined oral terbinafine. Participants with hyperkeratotic type tinea pedis were randomly assigned to two groups. Patients in group I were treated with oral terbinafine for 2 weeks and topical terbinafine and 10% urea ointment for 4 weeks, whereas in group II, only the above topical agents were applied for 12 weeks. Clinical improvement rates and fungal eradication rates were compared between the two groups at 24 weeks after the initiation of treatment. The group I had stopped the topical therapy 8 weeks earlier than group II. There were no significant differences in mycological eradication rates and clinical improvement rates between the two groups, besides, no major side effects were noted in both groups. The short combination therapy with oral terbinafine was effective and safe; it should be a valuable option for patients with hyperkeratotic type tinea pedis.

Cultural threads in writing mastery: a structural analysis of perfectionism, learning self-efficacy, and motivation as mediated by self-reflection in Chinese EFL learners.

BACKGROUND: The study explores language acquisition in Chinese English as a Foreign Language (EFL) education, where English proficiency is crucial for global opportunities. As China gains prominence, the demand for English skills rises beyond communication to include academic and business success. The Chinese education system emphasizes proficient English writing for further education and professional achievement. This research investigates the complex linguistic context for EFL learners in China, analyzing the intersection of psychological factors, cultural nuances, varied pedagogy, and individual experiences. METHODS: Structural Equation Modeling (SEM) is utilized for analysis, enabling the creation of a metric set to explore intangibles such as perfectionism, learning self-efficacy, motivation, study habits, cultural influences, and introspection. The research utilizes a diverse sample from multiple universities across different regions of China, incorporating demographic factors to encompass the varied characteristics within the EFL learner community. RESULTS: Results reveal that perfectionism (ß = 0.30, p < 0.001), learning self-efficacy (ß = 0.25, p = 0.005), motivation (ß = 0.35, p < 0.001), study habits (ß = 0.20, p = 0.01), and self-reflection (ß = 0.28, p < 0.001) significantly predict writing proficiency. Cultural effects (Beta = 0.15, p = 0.05) show a statistically significant, albeit minimal, impact. Mediation-moderation analysis underscores perfectionism as a mediator (Beta = 0.25, p = 0.005), emphasizing its influence on other predictors. Cultural factors act as moderators (Beta = 0.15, p = 0.01), shaping the link between predictors and writing skills. The combined mediation and moderation effects on writing proficiency are positively significant (Beta = 0.20, p = 0.02). CONCLUSIONS: This study makes a significant theoretical contribution, enhancing existing models and providing practical insights for EFL educators and policymakers. Emphasizing the intricate relationship between psychological factors and cultural dynamics underscores the necessity for a sophisticated, culturally sensitive approach to language acquisition in Chinese EFL instruction. Beyond language skills, the research recognizes the importance of fostering a conducive environment that encourages personal development, socio-cultural awareness, and a holistic learning approach.

Death-Associated Protein-1 Plays a Role in the Reproductive Development of Nilaparvata lugens and the Transovarial Transmission of Its Yeast-Like Symbiont.

Death-associated protein-1 (DAP-1) plays a crucial role in cell growth, migration, autophagy, and apoptosis in mammals. However, its function in insects remains unclear. In the present study, we cloned and identified Nilaparvata lugens DAP-1 (NlDAP-1). NlDAP-1 was expressed during all developmental stages and in all tissues of N. lugens, being particularly higher in the ovaries of female adults. RNAi with double-stranded NlDAP-1 RNA significantly inhibited the expression of NlDAP-1, leading to premature death (dying seven days earlier), delayed ovarian development, and fewer offspring (76.7% reduction in eggs with 77.4% reduction in egg hatching rate). Additionally, an immunofluorescence experiment showed that NlDAP-1 was highly expressed when yeast-like symbionts (YLSs) entered N. lugens oocytes, and inhibiting the expression of NlDAP-1 disturbed the process; the RNAi of NlDAP-1 caused a 34.9% reduction in the YLSs that entered oocytes. These results indicate that NlDAP-1 plays a crucial role in the reproductive development of N. lugens and the transovarial transmission of its YLSs.

Relationship between bullous pemphigoid and malignancy: A Mendelian randomization study.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, which primarily affects the elderly. However, the relationship between BP and malignancy remains controversial in traditional observational studies. The aim of this study, which included only European populations, was to assess the potential causative link between BP and 13 types of malignant tumors in a two-sample Mendelian randomization (MR) study. BP was not associated with an increased risk of developing 13 types of malignant tumors. This study did not find a causal relationship between BP and malignant tumors. However, further research is warranted to examine the generalizability of this conclusion in non-European populations.

A SNP resource for Douglas-fir: de novo transcriptome assembly and SNP detection and validation.

BACKGROUND: Douglas-fir (Pseudotsuga menziesii), one of the most economically and ecologically important tree species in the world, also has one of the largest tree breeding programs. Although the coastal and interior varieties of Douglas-fir (vars. menziesii and glauca) are native to North America, the coastal variety is also widely planted for timber production in Europe, New Zealand, Australia, and Chile. Our main goal was to develop a SNP resource large enough to facilitate genomic selection in Douglas-fir breeding programs. To accomplish this, we developed a 454-based reference transcriptome for coastal Douglas-fir, annotated and evaluated the quality of the reference, identified putative SNPs, and then validated a sample of those SNPs using the Illumina Infinium genotyping platform. RESULTS: We assembled a reference transcriptome consisting of 25,002 isogroups (unique gene models) and 102,623 singletons from 2.76 million 454 and Sanger cDNA sequences from coastal Douglas-fir. We identified 278,979 unique SNPs by mapping the 454 and Sanger sequences to the reference, and by mapping four datasets of Illumina cDNA sequences from multiple seed sources, genotypes, and tissues. The Illumina datasets represented coastal Douglas-fir (64.00 and 13.41 million reads), interior Douglas-fir (80.45 million reads), and a Yakima population similar to interior Douglas-fir (8.99 million reads). We assayed 8067 SNPs on 260 trees using an Illumina Infinium SNP genotyping array. Of these SNPs, 5847 (72.5%) were called successfully and were polymorphic. CONCLUSIONS: Based on our validation efficiency, our SNP database may contain as many as ~200,000 true SNPs, and as many as ~69,000 SNPs that could be genotyped at ~20,000 gene loci using an Infinium II array-more SNPs than are needed to use genomic selection in tree breeding programs. Ultimately, these genomic resources will enhance Douglas-fir breeding and allow us to better understand landscape-scale patterns of genetic variation and potential responses to climate change.

Control of dissected leaf morphology by a Cys(2)His(2) zinc finger transcription factor in the model legume Medicago truncatula.

Plant leaves are diverse in their morphology, reflecting to a large degree the plant diversity in the natural environment. How different leaf morphology is determined is not yet understood. The leguminous plant Medicago truncatula exhibits dissected leaves with three leaflets at the tip. We show that development of the trifoliate leaves is determined by the Cys(2)His(2) zinc finger transcription factor PALM1. Loss-of-function mutants of PALM1 develop dissected leaves with five leaflets clustered at the tip. We demonstrate that PALM1 binds a specific promoter sequence and down-regulates the expression of the M. truncatula LEAFY/UNIFOLIATA orthologue SINGLE LEAFLET1 (SGL1), encoding an indeterminacy factor necessary for leaflet initiation. Our data indicate that SGL1 is required for leaflet proliferation in the palm1 mutant. Interestingly, ectopic expression of PALM1 effectively suppresses the lobed leaf phenotype from overexpression of a class 1 KNOTTED1-like homeobox protein in Arabidopsis plants. Taken together, our results show that PALM1 acts as a determinacy factor, regulates the spatial-temporal expression of SGL1 during leaf morphogenesis and together with the LEAFY/UNIFOLIATA orthologue plays an important role in orchestrating the compound leaf morphology in M. truncatula.

M1 macrophages may be effective adjuvants for promoting Th­17 differentiation in HBeAg positive hepatitis patients with ALT ≤2ULN.

Hepatitis B virus (HBV) infection can activate macrophages to accelerate liver disease progression, including inflammation and fibrosis. However, the exact mechanism remains undetermined. The present study assessed the effects of macrophage polarization and the related cytokines on Th­17 differentiation in HBeAg positive individuals with a HBV infection, and also evaluated the potential association of Th­17 cell frequency with the severity of liver injury. A cross­sectional study design was used to collect the clinical parameters, blood samples and liver tissue samples of patients with alanine transaminase £2x upper limit of normal and confirmed hepatitis B who underwent liver puncture in Qishan Hospital between January 2019­December 2021. Macrophage and Th­17 cell related factors were assayed using ELISA. The expression and quantification of cell surface antigen and intracellular markers in cells were assessed using flow cytometry. Pathological staining, including hematoxylin and eosin, reticular fiber staining and immunohistochemical staining were used to assess inflammation and fibrosis in the liver tissue. In the peripheral blood of patients with HBV infection, the number of CD14+ macrophages was significantly increased compared with the healthy control, especially in the hepatitis B e antigen (HBeAg) positive group. CD14+ macrophages were predominantly of the M1 type based on the assessment of the phenotype using flow cytometry and cytokine secretion. Furthermore, the percentage of M1 phenotype and related cytokines were positively correlated with Th­17 differentiation. IL­17A secreted by Th­17 was positively correlated with the degree of liver inflammation and fibrosis, as well as with the severity of liver disease, which indicated that the differentiation of Th­17 may be involved in the progression of liver disease. HBeAg may promote Th­17 differentiation and IL­17A production by M1 macrophages to accelerate the pathogenesis of liver inflammation and fibrosis in CHB patients.

Molecular Characterization and RNA Interference Analysis of SLC26A10 From Nilaparvata lugens (Stål).

SLC26A10 is a member of the SLC26 gene family, but its role in insects is still unclear. We cloned the SLC26A10 gene of Nilaparvata lugens (NlSLC26A10) and found NlSLC26A10 contained 11 transmembrane regions and a STAS domain. Expression pattern analysis showed NlSLC26A10 expression was more upregulated in adults than in nymphs, highest in the ovary. After injection of double-stranded RNA (dsRNA) of NlSLC26A10, the mRNA level of NlSLC26A10 significantly decreased and, consequently, the ovarian development of adult females was hindered; the amount and the hatchability of eggs and yeast-like symbionts in mature oocytes decreased. Further study showed that NlSLC26A10 might result in decreased juvenile hormone level and vitellogenin expression. These results indicate that NlSLC26A10 plays an essential role in the reproduction of N. lugens.

Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 Plays an Important Role in the Development and Reproduction of Nilaparvata lugens.

The brown planthopper, Nilaparvata lugens, is a difficult-to-control insect pest affecting rice yields in Asia. As a structural component of the inter-alpha-trypsin inhibitor (ITI), the inter-alpha-trypsin inhibitor heavy chain (ITIH) has been reported to be involved in various inflammatory or malignant disorders, ovarian development, and ovulation. To reveal the function of ITIH4 in N. lugens, the gene encoding N. lugens ITIH4 (NlITIH4) was cloned and characterized. NlITIH4 contains a signal peptide, a vault protein inter-alpha-trypsin domain, and a von Willebrand factor type A domain. qPCR analysis showed that NlITIH4 was expressed at all developmental stages and in all tissues (fat body, ovary, and gut), with the highest expression in the fat body. Double stranded NlITIH4 (dsNlITIH4) injection clearly led to an RNAi-mediated inhibition of the expression of NlITIH4 and resulted in reduced survival, delayed ovarian development, and reduced egg production and egg hatching. These results indicate that NlITIH4 plays an important role in the development and reproduction of N. lugens.

Treatment of psoriasis with recombinant human LFA3-antibody fusion protein: a multi-center, randomized, double-blind trial in a Chinese population.

To evaluate clinical efficacy and safety of injectable recombinant human LFA3-antibody fusion protein (rhLFA3-IgFP), a multi-center, randomized, double-blind, double-dummy, parallel-controlled clinical trial was performed in 212 cases of moderate to severe psoriasis. Intramuscular injection of rhLFA3-IgFP (15 mg/week) and oral administration of blank dummy methotrexate at the dose of 7.5 mg/week was performed in the patients in the experimental group, and control patients were orally administered with methotrexate at the dose of 7.5 mg/week and intramuscularly injected with the blank dummy rhLFA3-IgFP (15 mg/week). PASI was determined prior to and at 2, 4, 6, 8, 12, 16, 20 weeks after the treatment. The efficacy evaluation was carried out on 192 patients, and no significant differences were found in PASI50, PASI75 & PASI90 between the two groups after twelve weeks' treatment (p>0.05). After discontinuation, PASI scores continued to decrease drastically in the experiment group, whereas they increased in the control group. At 8 weeks after discontinuation, PASI scores were decreased by 62.32% (p<0.05) and 52.67% (p<0.05) in the experimental and control groups, respectively. No serious adverse reactions were observed. In conclusion, the results of our investigation demonstrated that rhLFA3-IgFP was an effective therapy for chronic plaque psoriasis with lasting action and low incidence of adverse reactions.

LncRNA NORAD engages in psoriasis by binding to miR-26a to regulate keratinocyte proliferation.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. It was reported that lncRNA Non-coding RNA-activated by DNA damage (NORAD) has potential regulatory effects on skin diseases. Our previous studies found that lncRNA NORAD was highly expressed and its potential target miR-26a was down-regulated in psoriasis model mice. Here, we aimed to investigate the role of NORAD in the development of psoriasis. METHODS: IL-22/LPS (interleukin-22/lipopolysaccharide)-stimulated HaCaT (human immortalized keratinocytes) cell model and imiquimod-induced mouse model were established. Keratin 6 (K6), Keratin 16 (K16), Keratin 17 (K17), and Cell division cycle 6 (CDC6) levels were detected by western blot. Cell activity was detected by CCK-8, MTT, and EdU assays. Quantitative real-time PCR was performed to examine the levels of NORAD, miR-26a, CDC6, K6, K16, and K17. Haematoxylin-eosin staining was applied to observe the degree of skin thickening and hyperplasia. Fluorescence in situ hybridization detects the location of NORAD. RNA immunoprecipitation, RNA pull-down, and Luciferase test were performed to detect the interaction between NORAD and miR-26a. RESULTS: In IL-22/LPS-stimulated HaCaT cells, NORAD, CDC6, and keratinocyte proliferation-related proteins (K6, K16, and K17) were up-regulated and miR-26a was down-regulated. Cell survival and proliferation were also increased. However, the results were reversed after interference with NORAD. Also, in vitro experiments revealed that NORAD negatively regulated miR-26a. In IL-22/LPS-stimulated HaCaT cells and skin of imiquimod-induced mice, we found that lower NORAD resulted in an increase of miR-26a and a decrease of CDC6, further decreased levels of keratinocyte proliferation-related proteins (K6, K16, and K17).