NTSM: a non-salient target segmentation model for oral mucosal diseases.

BACKGROUND: Oral mucosal diseases are similar to the surrounding normal tissues, i.e., their many non-salient features, which poses a challenge for accurate segmentation lesions. Additionally, high-precision large models generate too many parameters, which puts pressure on storage and makes it difficult to deploy on portable devices. METHODS: To address these issues, we design a non-salient target segmentation model (NTSM) to improve segmentation performance while reducing the number of parameters. The NTSM includes a difference association (DA) module and multiple feature hierarchy pyramid attention (FHPA) modules. The DA module enhances feature differences at different levels to learn local context information and extend the segmentation mask to potentially similar areas. It also learns logical semantic relationship information through different receptive fields to determine the actual lesions and further elevates the segmentation performance of non-salient lesions. The FHPA module extracts pathological information from different views by performing the hadamard product attention (HPA) operation on input features, which reduces the number of parameters. RESULTS: The experimental results on the oral mucosal diseases (OMD) dataset and international skin imaging collaboration (ISIC) dataset demonstrate that our model outperforms existing state-of-the-art methods. Compared with the nnU-Net backbone, our model has 43.20% fewer parameters while still achieving a 3.14% increase in the Dice score. CONCLUSIONS: Our model has high segmentation accuracy on non-salient areas of oral mucosal diseases and can effectively reduce resource consumption.

Chondroitin sulfate/silk fibroin hydrogel incorporating graphene oxide quantum dots with photothermal-effect promotes type H vessel-related wound healing.

Chronic wounds with bacterial infection present formidable clinical challenges. In this study, a versatile hydrogel dressing with antibacterial and angiogenic activity composite of silk fibroin (SF), chondroitin sulfate (CS), and graphene oxide quantum dots (GOQDs) is fabricated. GOQDs@SF/CS (GSC) hydrogel is rapidly formed through the enzyme catalytic action of horseradish peroxidase. With the incorporation of GOQDs both gelation speed and mechanical properties have been enhanced, and the photothermal characteristics of GOQDs in GSC hydrogel enabled bacterial killing through photothermal treatment (PTT) at ∼51 °C. In vitro studies show that the GSC hydrogels demonstrate excellent antibacterial performance and induce type H vessel differentiation of endothelial cells via the activated ERK1/2 signaling pathway and upregulated SLIT3 expression. In vivo results show that the hydrogel significantly promotes type H vessels formation, which is related to the collagen deposition, epithelialization and, ultimately, accelerates the regeneration of infected skin defects. Collectively, this multifunctional GSC hydrogel, with dual action of antibacterial efficacy and angiogenesis promotion, emerges as an innovative skin dressing with the potential for advancing in infected wound healing.

Possible interplay of diabetes mellitus and thyroid diseases in oral lichen planus: A pooled prevalence analysis.

The existence of a comorbidity between diabetes mellitus (DM) as well as between thyroid diseases (TD) and oral lichen planus (OLP), respectively, was substantially demonstrated. However, there is not enough attention to the concurrent status of both TD and DM in OLP patients. Herein, this short communication aimed to compare 1) the prevalence of DM when TD was concurrently investigated and that of DM when TD status was ignored; 2) the prevalence of TD when DM was concurrently investigated and that of TD when DM status was ignored in the studies. The pooled prevalence (9.86 %; 95 % confidence intervals [CI], 9.22-10.53 %) of DM when TD was concurrently investigated was significantly higher than that (8.13 %; 95%CI, 8.03-9.12 %) when TD status was not investigated in OLP patients. The pooled prevalence (12.48 %; 95%CI, 11.77-13.22 %) of TD when DM was concurrently investigated was significantly higher than that (10.45 %; 95%CI, 9.52-11.46 %) when DM status was not investigated in OLP patients. Thus, it is logical to presume for the first time that there is possible interplay of DM and TD in OLP occurrence. TD and DM should serve as important confounding factors each other in clinical investigation on OLP and associated comorbidities.

Decreased ZMIZ1 suppresses melanogenesis in vitiligo by regulating mTOR/AKT/GSK-3ß-mediated glucose uptake.

The loss of epidermal melanocytes is a distinguishing feature of vitiligo (VIT), a prevalent and long-lasting skin ailment. While various hypotheses exist to explain the cause of VIT, the precise mechanisms leading to this disease remain unclear. Zinc finger MIZ-type containing 1 (ZMIZ1) has a strong link with the development and occurrence of VIT. However, the exact role of ZMIZ1 and its underlying mechanisms in VIT are not well understood. Our study aims to illustrate that targeting ZMIZ1 is an effective therapeutic and prophylactic strategy for treating VIT. We obtained the RNA expression profile of VIT samples using RNA-seq and determined the locations and expression of ZMIZ1 in these samples via immunochemistry. Glucose uptake was analyzed through immunofluorescence and glucose uptake assay. We evaluated mRNA levels using qPCR and used plasmids transfection to knock down ZMIZ1 in PIG1 and PIG3V cell lines. The activation of the mTOR/AKT/GSK-3ß signalling pathway was assessed using Western blotting analysis. We found that ZMIZ1 expression was decreased in VIT samples. Decreased ZMIZ1 expression inhibits the proliferation, migration, and invasion of melanocytes in vitro. Moreover, we revealed that decreased ZMIZ1 could also inhibit the glucose uptake of melanocytes in vitro. Decreased ZMIZ1 expression inhibits the activation of the mTOR/AKT/GSK-3ß pathway and the expression of melanin synthesis-related proteins in melanocytes. Finally, we demonstrated that decreased ZMIZ1 may inhibit the cell viability of melanocytes and the synthesis of melanin by mTOR/AKT/GSK-3ß-mediated oxidative stress in vitro. In conclusion, our study suggests that decreased ZMIZ1 suppresses melanogenesis in vitiligo by regulating the mTOR/AKT/GSK-3ß-mediated glucose uptake in vitro, making ZMIZ1 an attractive therapeutic target for the treatment of VIT.

POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, but its occurrence and progression mechanisms remain unclear. In addition-there is a lack of effective targeting drugs. The second major subunit of DNA polymerase (POLE2) catalyzes the prolongation of new strand replication and modifies exonuclease domain activity. Our previous study found that POLE2 was associated with OSCC progression, but the mechanism remains unclear. METHODS: The expression of POLE2 in OSCC tissues was detected using immunological assays. Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC. POLE2 expression was inhibited in OSCC cells, and the effects of gene and protein expression were detected using RT-PCR and Western blotting. The POLE2 knockout model was constructed by transfecting a lentiviral vector. Cell proliferation, apoptosis, and migration were detected using various assays including colony formation, MTT, flow cytometry, wound healing assay, Transwell assay, and the Human Apoptosis Antibody Array. The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice. After 30 days, tumors were removed under anesthesia and tumor weight and dimension were recorded. Tumor cell proliferation was analyzed using Ki67 staining. RESULTS: POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues. In addition, POLE2 gene levels were statistically correlated with tumor classification and prognosis. Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro. Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation. We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3, CD40, CD40L, DR6, Fas, IGFBP-6, p21, and SMAC. In addition, POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway. CONCLUSION: POLE2 is closely related to the progression of OSCC. Thus, POLE2 may be a potential target for OSCC treatment.

Pemphigus and pemphigoid research by dermatologists and stomatologists: A scientometric and comparative study.

Background/purpose: Pemphigus and pemphigoid are systemic bullous autoimmune diseases affecting skin and/or mucosal membranes with the life-threatening nature, especially pemphigus vulgaris. The papers published by dermatologists and stomatologists preferentially represent their concerns of a mucocutaneous disease. Materials and methods: The objective of this study was to compare the scientometric characteristics of pemphigus and pemphigoid publications by dermatologists and stomatologists in the Scopus database. Results: There are 9276 and 760 papers published by dermatologists and stomatologists, respectively. The annual number of the publications by dermatologists stably raised from 218 to 526 during 2007-2022; while the number by stomatologists raised with a small amount from 18 to 51 during this period. For the most-cited top-200 papers, the total citation count is 42,766 and the h index is 148 for pemphigus publications by dermatologists; whereas the count is 14,689 and h index is 63 for publications by stomatologists. Notably, first signs of pemphigus often appear in oral mucosa, manifesting as erythema, blisters, as well as mouth ulcer, gingivitis, lichen planus-like pemphigus. Conclusion: This study firstly reports the scientometric characteristics of pemphigus publications by dermatologists and stomatologists. The scale and citations of dermatologists' publications greatly outweigh stomatologists' ones, suggesting stomatologists can learn from and more cooperate with dermatologists regarding pemphigus research.

Identifying immuno-related diagnostic genes and immune infiltration signatures for periodontitis and alopecia areata.

BACKGROUND: Although there have been indications that periodontitis (PD) may be susceptible to alopecia areata (AA), the underlying mechanism of its pathogenesis remains poorly understood. The objective of our study is to conduct further research into the occurrence of this complication. METHODS: The gene expression omnibus (GEO) database was the source of acquisition for both PD and AA datasets. Various methods, including the differentially expressed genes (DEGs) analysis, functional enrichment analysis, protein-protein interaction (PPI) network construction, Cytohubba algorithms, and RandomForest algorithms, were utilized to identify candidate hub immuno-related genes (IRGs) for diagnosing AA with PD. The diagnostic efficacy was assessed by constructing receiver operating characteristic (ROC) curves. To further deepen our understanding, immune cell infiltration, flow cytometry assay, and immunofluorescence techniques were employed to uncover immune cell dysregulation in PD and AA. RESULTS: 899 and 803 DEGs were detected in AA and PD, respectively, with an intersection of 150 common DEGs enriched in immune regulation. Further analysis of the junction of shared DEGs and IRGs was analyzed using the PPI network, Mcode, and Cytohubba algorithms. Three hub genes (CTSS, IL2RG, and ITGAL) were subsequently selected by Cytohubba and RandomForest algorithms and were found to be promising candidate hub genes with high diagnostic values (AUC ranging from 0.776 to 0.909) for diagnosing AA with PD. Additionally, various dysregulated immune cells were observed, with mast cells potentially serving as markers for AA and plasma for PD. CONCLUSION: Three candidate hub IRGs (CTSS, IL2RG, and ITGAL) were identified with considerable diagnostic values. Besides, mast cells could serve as markers for AA, while plasma may indicate PD. Our research has the potential to identify shared diagnostic candidate genes and immune cells for AA and PD patients.

A machine learning study on the fatigue crack path of short crack on an α titanium alloy.

In the present study, a physics-informed neural network model based on Bayesian hyperparameter optimization is proposed for the prediction of short crack growth paths. A large number of cyclic loadings at a lower amplitude were applied to an α titanium sample by an ultrasonic fatigue machine to ensure a sufficient amount of data for machine learning. The grain size, grain orientation and grain boundary direction on the path, as well as crack growth direction, were selected as feature data for training the prediction model. The optimizations of the size ratio and the angle operation were conducted to compare different data processing methods, respectively. After evaluation, eventually, a model for predicting crack growth path is obtained with a reliable performance of 10% tolerance on the path angle at each grain boundary. And the prediction effect of the proposed model is better than that of some classic machine learning models and slip trace analysis. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Cryptococcosis Inhibits the Immune Response of Dendritic Cells Through the snhg1-miR-145a-3p-Bcl2 Axis.

OBJECTIVES: Dendritic cells are one of the first host cells that cryptococcus encounters. However, the correlations among cryptococcus, dendritic cells, and long noncoding RNA remain unclear. This study was undertaken to investigate the effects of long noncoding RNAs on dendritic cells with cryptococcus infection. MATERIALS AND METHODS: We treated dendritic cells with cryptococcus and then detected expression of CD80, CD86, and major histocompatibility complex class II in dendritic cells with a real-time fluorescent quantitative polymerase chain reaction assay. We used nextgeneration sequencing and bioinformatics analysis to determine the competitive endogenous RNA mechanisms, confirmed via real-time polymerase chain reaction, dual luciferase reporter, and RNA-binding protein immunoprecipitation assays. RESULTS: After treatment of dendritic cells with 1 × 108 CFU/mL cryptococcus for 12 hours, dendritic cell viability was normal, whereas mRNA expression levels of CD80, CD86, and major histocompatibility complex class II in dendritic cells were substantially increased. With next-generation sequencing, we discovered 4 small nucleolar RNA host genes (snhg1, snhg3, snhg4, and snhg16) in cryptococcus-treated dendritic cells compared with wild-type dendritic cells. Bioinformatics analysis combined with real-time polymerase chain reaction led us to speculate that cryptococcus may affect the maturation and apoptosis of dendritic cells by regulating snhg1-miR-145a-3p-Bcl2. Further polymerase chain reaction, dual luciferase reporter, and RNA-binding protein immunoprecipitation experiments revealed that snhg1 acted as a sponge for miR145a-3p to inhibit the expression of miR-145a-3p and that miR-145a-3p promoted the expression of Bcl2 by directly targeting the 3'-UTR of Bcl2. Functional recovery experiments showed that cryptococcus promoted the maturation and apoptosis and inhibited the proliferation of dendritic cells through the snhg1-Bcl2 pathway. CONCLUSIONS: This study lays a foundation for the further understanding of the pathogenic role of snhg1-miR-145a-3p-Bcl2 axis in cryptococcosis.

Association of polymorphisms in Th1/Th2-related cytokines (IFN-γ, TGFß1, IL-1ß, IL-2, IL-4, IL-18) with oral lichen planus: A pooled analysis of case-control studies.

Background/purpose: Increasing evidence suggests that single-nucleotide polymorphisms (SNPs) in Th1/Th2-related cytokine genes correlated with oral lichen planus (OLP) susceptibility. However, these results were inconsistent and inconclusive. Hence, the aim of this study is to draw a more precise estimation of the genetic associations between SNPs in 6 cytokines (IFN-γ, IL-18, TGFß1, IL-1ß, IL-2, IL-4) and OLP. Materials and methods: A systematic literature search was conducted to identify all eligible case-control studies on the association between SNPs in 6 cytokines and OLP susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. Results: A significant association of IFN-γ (874A/T) polymorphism with OLP was found (OR, 1.49; 95%CI, 1.22-1.81; P < 0.001) based on 6 eligible studies. A significant association of IL-18 (137G/C) polymorphism with OLP was found (OR, 1.64; 95%CI, 1.24-2.18; P < 0.001) based on 3 studies. A marginally significant association of TGFß1 (509C/T) polymorphism in allele model with OLP was found (OR, 1.31; 95%CI, 1.01-1.71; P = 0.05) based on 4 studies. Nevertheless, lack of significant association of IL-1ß (3954C/T), IL-2 (330T/G), IL-4 (590C/T), and IL-18 (607C/A) polymorphisms with OLP was found (P > 0.05) based on 3 studies, respectively. Conclusion: This is the first meta-analysis to investigate the associations of 6 cytokines polymorphisms with OLP, suggesting that SNPs in IFN-γ, IL-18, and TGFß1 may act as genetic factors for OLP risk. Further well-designed studies with larger sample size and multiple ethnicities are needed to validate these associations.

[Identification of circular RNA expression profiles in oral lichen planus].

PURPOSE: To construct the expression profile of circular RNA (circRNA) in human oral lichen planus (OLP), and to identify and validate the differentially expressed circRNA in oral lichen planus tissues and provide theoretical basis for the diagnosis and treatment of this disease. METHODS: Six patients newly diagnosed with OLP from September to December 2018 in the Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital and 6 healthy volunteers were enrolled in this study. RNA sequencing and evaluation in OLP tissues and normal oral mucosa were performed by high-throughput RNA sequencing technology, and the differences between groups were analyzed. qRT-PCR was used to validate the results. Statistical analysis was conducted with SPSS 24.0 software package. Finally, bioinformatics techniques GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway were used to analyze the functions and related pathways of the dysregulated genes. RESULTS: According to the sequencing results, 85 differentially expressed circRNAs with fold change > 2 were identified in OLP tissues compared to the normal oral mucosa, including 66 upregulated circRNAs and 19 downregulated circRNAs. Three circRNAs with the most significant up-regulation and down-regulation were selected for qRT-PCR verification in expanded samples, and the results were consistent with the sequencing results. Bioinformatics analysis suggested that the differentially expressed circRNAs may play an important role in the occurrence and progression of oral lichen planus. CONCLUSIONS: Differentially expressed circRNAs between oral lichen planus tissues and normal oral mucosa were identified, which may be involved in the pathogenic mechanism of oral lichen planus and could be potential biomarkers for diagnosis and treatment of this disease.

RNA-Seq based transcriptome analysis in oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a T cell-mediated autoimmune disease recognized as an oral potential malignant disorder (OPMD) with the precise mechanism unknown. This study focused on the transcriptional profiles of OLP to elucidate its potential pathogenesis. METHODS: We conducted RNA sequencing on matched 6 OLP tissues and 6 normal oral mucosal tissues. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and weighted gene co-expression network analysis (WGCNA) were performed on differentially expressed genes (DEGs). We utilized qRT-PCR to validated the top dysregulated genes and hub genes in another 10 pairs of specimens. RESULTS: A total of 153 DEGs (p-values< 0.05) were detected from RNA-Seq. According to GO and KEGG analysis, the dysregulated genes were mainly related to T cell related pathway and Wnt signaling. Based on the WGCNA analysis, 5 modules with high intramodular connectivity and hub genes in each module were gained. CONCLUSIONS: RNA-Seq and bioinformatic methods offered a valuable understanding of the biological pathways and key genes in the regulation of OLP. The identified DEGs and hub genes categorized into 2 groups including T cell regulation and inflammation and Wnt signaling pathway may serve as potential novel molecular targets for therapy.

Epidermal stimulating factors-gelatin/polycaprolactone coaxial electrospun nanofiber: ideal nanoscale material for dermal substitute.

In this study, an ideal nano-scale material, named epidermal stimulating (ES) factors-gelatin/polycaprolactone (GT/PCL) nanofiber, was fabricated using a coaxial electrospinning technique. The ES-GT/PCL nanofibers possessed a highly porous structure with qualified mechanical properties for transplantation. With ES factors stored in the core and GT/PCL in the shell, the ES factors could be protected and released in a sustained manner. After seeding L929 cell line on ES-GT/PCL nanofibers for 7 days in vitro, the proliferation of cells was nearly 1.5 folds compared to the control group. The in vivo study showed that ES-GT/PCL nanofibers can accelerate skin wound healing rate during the healing course, especially on the early stage. The epidermal and dermal thickness, as well as skin appendages and fat tissue, were the most similar to the native skin. These findings provided valuable insights into the addition of multiple bioactive factors to nanometre biomaterials, and optimising the advantages of the compositions as a promising potential dermal substitute construct.

Regeneration of Subcutaneous Cartilage in a Swine Model Using Autologous Auricular Chondrocytes and Electrospun Nanofiber Membranes Under Conditions of Varying Gelatin/PCL Ratios.

The scarcity of ideal biocompatible scaffolds makes the regeneration of cartilage in the subcutaneous environment of large animals difficult. We have previously reported the successful regeneration of good-quality cartilage in a nude mouse model using the electrospun gelatin/polycaprolactone (GT/PCL) nanofiber membranes. The GT/PCL ratios were varied to generate different sets of membranes to conduct the experiments. However, it is unknown whether these GT/PCL membranes can support the process of cartilage regeneration in an immunocompetent large animal model. We seeded swine auricular chondrocytes onto different GT/PCL nanofiber membranes (GT:PCL = 30:70, 50:50, and 70:30) under the sandwich cell-seeding mode. Prior to subcutaneously implanting the samples into an autologous host, they were cultured in vitro over a period of 2 weeks. The results revealed that the nanofiber membranes with different GT/PCL ratios could support the process of subcutaneous cartilage regeneration in an autologous swine model. The maximum extent of homogeneity in the cartilage tissues was achieved when the G5P5 (GT: PC = 50: 50) group was used for the regeneration of cartilage. The formed homogeneous cartilage tissues were characterized by the maximum cartilage formation ratio. The extents of the ingrowth of the fibrous tissues realized and the extents of infiltration of inflammatory cells achieved were found to be the minimum in this case. Quantitative analyses were conducted to determine the wet weight, cartilage-specific extracellular matrix content, and Young's modulus. The results indicated that the optimal extent of cartilage formation was observed in the G5P5 group. These results indicated that the GT/PCL nanofiber membranes could serve as a potential scaffold for supporting subcutaneous cartilage regeneration under clinical settings. An optimum GT/PCL ratio can promote cartilage formation.

Altered expression of CCN1 in oral lichen planus associated with keratinocyte activation and IL-1ß, ICAM1, and CCL5 up-regulation.

BACKGROUND: Emerging evidence indicates that CCN1 is a novel inflammation-regulated mediator involved in the pathogenesis of some immune-mediated inflammatory diseases. The objective of this study was to investigate the preliminary roles of CCN1 and its related cytokines IL-1ß, CCL5, and ICAM1 in oral lichen planus (OLP). METHODS: CCN1 expression levels in biopsies from OLP patients against normal oral mucosa (NOM) using immunohistochemistry (42 OLP vs 9 NOM) and RT-qPCR (20 OLP vs 20 NOM) were compared, respectively. The correlation of CCN1 and IL-1ß, CCL5, and ICAM1 expression was examined by RT-qPCR in tissue samples and an in vitro cell culture system using keratinocyte HaCaT cells incubated with lipopolysaccharides. RESULTS: Immunohistochemistry showed that CCN1 protein mainly expressed in the cytoplasm of epithelial keratinocytes of OLP. Consistently, RT-qPCR revealed that mRNA expression of CCN1 was increased in OLP compared with NOM (P < .05) and positively correlated with the high expression of IL-1ß, ICAM1, and CCL5 (P < .001), respectively. Importantly, an in vitro study showed that keratinocyte proliferation significantly (P < .05) increased by CCN1 stimulation. Moreover, IL-1ß, ICAM1, and CCL5 expression in keratinocytes stimulated by CCN1 was increased (P < .05), respectively. CONCLUSIONS: This preliminary study for the first time reported that altered expression of CCN1 was associated with high expression of IL-1ß, ICAM1, and CCL5 in OLP. And we demonstrated CCN1 promoted keratinocyte activation, as well as IL-1ß, ICAM1, and CCL5 production in keratinocytes. Our data indicated that the potential role of CCN1 and its related cytokines was involved in the pathogenesis of OLP.

Research trends and characteristics of oral lichen planus: A bibliometric study of the top-100 cited articles.

BACKGROUND: Bibliometric analysis highlights the key topics and research trends which have shaped the understanding and management of a concerned disease. The objective of this study was to identify and characterize the most-cited articles on oral lichen planus (OLP), and highlight the analysis of key topics and research trends. METHODS: A comprehensive search was performed and identified in the Scopus database from 1907 to 5 March 2019 for the top-100 most-cited articles on OLP. RESULTS: The number of citations of the 100 selected articles varied from 101 to 570, with a mean of 178.7 citations per article. Malignant potential, immunopathogenesis, and topical drug therapy were the top-3 study topics, and the majority of high-quality articles were the research of the 3 topics. Journal of Oral Pathology and Medicine (n = 19) and Oral Surgery Oral Medicine Oral Pathology Oral Radiology (n = 14) were 2 journals with the most articles published. Both van der Waal I. and Scully C. were the most frequently contributing authors (n = 9). United States (n = 27) and Academic Centre for Dentistry Amsterdam (n = 7) was the most contributing country and institution, respectively. Systematic reviews (n = 2), randomized controlled trial (n = 1), cohort studies (n = 17) were study designs with higher evidence level, but the large majority (n = 80) were considered lower level. CONCLUSIONS: The results of this first citation analysis of the 100 most cited articles on OLP provide a historical perspective on scientific evolution, and suggest further research trends and clinical practice in the field of OLP.

Cyr61/CCN1 induces CCL20 production by keratinocyte via activating p38 and JNK/AP-1 pathway in psoriasis.

BACKGROUND: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood. OBJECTIVE: In this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte. METHODS AND RESULTS: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion. Furthermore, in vivo, blocking or knockdown CCN1 expression ameliorated skin inflammation and reduced the expression of CCL20 in both imiquimod and IL-23-induced psoriasis-like mouse models, which indicated that CCN1 might be involved in the regulation of CCL20 production in psoriasis. Next, in vitro, we stimulated primary normal human epidermal keratinocyte (NHEK) with exogenous protein CCN1 and found that CCN1 directly upregulated CCL20 production independent of TNF-α, IL-22 and IL-17 pathway. Lastly, the signaling pathway study showed that CCN1 enhanced the binding of AP-1 to the CCL20 promoter via crosstalk with p38 and JNK. CONCLUSIONS: Our study demonstrates that CCN1 stimulates CCL20 production in vitro and in vivo, and thus supports the notion that overexpressed CCN1 in hyperproliferating keratinocyte is functionally involved in the recruitment of inflammatory cells to skin lesions affected by psoriasis.

Altered expression of interleukin-17A and its targeting microRNAs in oral lichen planus: a pilot study.

OBJECTIVE: To investigate the potential role of interleukin (IL)-17A and its targeting microRNAs (miRNAs) in oral lichen planus (OLP). STUDY DESIGN: We compared the IL-17A expression levels in biopsies from patients with OLP (n = 50) against normal controls (n = 19) by using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses, identified the targeting miRNAs of IL-17A, and examined the miRNA expression levels in OLP. RESULTS: IL-17A expression was significantly increased in patients with OLP compared with controls. The dual-luciferase reporter assay system demonstrated that miR-635 and miR-578 were the target miRNAs of IL-17A in human embryonic kidney 293 cells, which was consistent with predictions from bioinformatics software analyses. In contrast with IL-17A, the expression levels of miR-635 and miR-578 in OLP were significantly decreased compared with controls. CONCLUSIONS: This pilot study found that low levels of miR-635 and miR-578 expression were associated with high expression of IL-17A, suggesting that IL-17A and its targeting miRNAs contribute to the pathogenesis of OLP.

Aberrant expression of interleukin-22 and its targeting microRNAs in oral lichen planus: a preliminary study.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated autoimmune disease involving oral mucosa. Interleukin-22 (IL-22) as the signature cytokine of T helper 22 cells is increasingly recognized as a key regulator in various autoimmune diseases. Our previous study reported that IL-22 immunoexpression in OLP was significantly increased compared with the normal controls. METHODS: The objective of this preliminary study was to compare the IL-22 expression levels in oral biopsies from patients with OLP (n = 50) against normal oral mucosa (n = 19) using RT-qPCR and Western blot, identify the potential targeting miRNAs of IL-22, and examine the miRNA expression levels in OLP. RESULTS: Interleukin-22 expression level in OLP was significantly increased compared with the normal controls. The Dual-Luciferase reporter assay system in human embryonic kidney 293 (HEK293) cells demonstrated that miR-562 and miR-203 were the target miRNAs of IL-22, which was consistent with predictions from bioinformatics software analyses. Interestingly, miR-562 expression in OLP was significantly decreased, but miR-203 expression in OLP was significantly increased compared with the normal controls. CONCLUSION: This preliminary study for the first time reported that aberrant expression levels of miR-562 and miR-203 were associated with high expression of IL-22 and demonstrated the target relationship between miRNAs and IL-22 in HEK293 cells. Our data indicated that IL-22 and its targeting miRNAs contribute to the pathogenesis of OLP. Further studies are required to investigate the regulatory pathways of IL-22 and miR-562 and miR-203 in OLP.