Search

Although Androgenetic Alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, the changes in the immune microenvironment, the immune-related pathway and the expression of Immune-related genes (IRGs) involved in AGA remain unclear. The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. Gene Set Enrichment Analysis (GSEA) among statistically changed genes was done. KEGG and GO analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The four hub IRGs, including MMP9, PTPRC, BMP2 and THBS1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

Background Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear. Objective We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE. Method RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis. Results The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P Conclusion Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease defined by the production of autoantibodies and involves multiple organs and systems. Although there are reports on SLE, data on its pathogenesis is limited. METHODS: Using R language software, we constructed a competing endogenous RNA (ceRNA) network. We then utilized the Search Tool for Recurring Instances of Neighbouring Genes (STRING) and cytoHubba databases to generate a protein-protein interaction (PPI) network, which led to the identification of hub genes. The top two hub genes with the highest Maximal Clique Centrality (MCC) score in the PPI network were further validated via quantitative real-time polymerase chain reaction (qRT-PCR) using in-house clinical samples. Also, weighted gene co-expression network analysis (WGCNA) with genes from the Gene Expression Omnibus Series (GSE)121239 dataset identified hub modules that were associated with clinical indicators. In addition, the genes contained in key modules as obtained by WGCNA were enriched and analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. The top hub gene, X-linked apoptosis inhibitory protein-associated factor (XAF1), was then identified by intersection of the PPI and WGCNA outcomes, and a pan-cancer analysis of this hub gene was subsequently performed. RESULTS: We comprehensively profiled the expression of Circular RNAs (circRNAs), MicroRNAs (miRNAs), and messenger RNAs (mRNAs) in SLE. We identified a hub gene, XAF1, based on evidence from the ceRNA network, WGCNA key module genes, and PPI network analyses. Moreover, qRT-PCR analysis demonstrated that the expression of XAF1 was significantly upregulated in SLE. Through the pan-cancer analysis, we demonstrated the common molecular roles of XAF1 in the pathogenesis of SLE and tumors, especially cutaneous melanoma. CONCLUSIONS: XAF1 is a key molecular biomarker in SLE. The pan-cancer analysis in this study provided shared genomic characteristics in SLE and cancers, especially for skin cutaneous melanoma (SKCM).

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR’97), 2012 Systemic Lupus International Collaborating Clinics (SLICC’12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR’19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC’12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR’19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.

Supplemental material, sj-pdf-1-lup-10.1177_0961203320959716 for A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum by Hui Jin, Tao Huang, Ruifang Wu, Ming Zhao, Haijing Wu, Hai Long, Heng Yin, Jieyue Liao, Shuangyan Luo, Yu Liu, Qing Zhang, Peng Zhang, Yixin Tan, Shuaihantian Luo, Xin Huang, Yaxiong Deng, Wei Liao, Liu Duan, Jianbo Chen, Yin Zhou, Jinghua Yin, Hong Qiu, Jin Yuan, Zijun Wang, Mengying Li, Xiaoqi Wu, Lina Chen, Liangmin Cai, Cancan Huang, Qianwen Li, Bingsi Tang, Bihui Yu, Xin Li, Xiaofei Gao, Yixi Hu, Xiaolei Ren, Haofan Xue, Zhangming Wei, Jinwei Chen, Fen Li, Guanghui Ling, Hui Luo, Hongjun Zhao, Sen Yang, Yong Cui, Youkun Lin, Xu Yao, Lingyun Sun, Qing Guo, Hong Fang, Kang Zeng, Danqi Deng, Jianzhong Zhang, Yuzhen Li, Xiongming Pu, Xiangping Liao, Xiqiang Dang, Danlin Huang, Yumei Liang, Qing Sun, Hongju Xie, Li Zeng, Cibo Huang, Qingchun Diao, Juan Tao, Jianbin Yu, Zhenlu Li, Hanshi Xu, Hui Li, Wei Lai, Xiguang Liu, Jingjing Wu, Tienan Li, Tiechi Lei, Qiuning Sun, Yanjia Li, Guoqiang Zhang, Xin Huang and Qianjin Lu in Lupus

Supplemental material, sj-pdf-2-lup-10.1177_0961203320959716 for A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum by Hui Jin, Tao Huang, Ruifang Wu, Ming Zhao, Haijing Wu, Hai Long, Heng Yin, Jieyue Liao, Shuangyan Luo, Yu Liu, Qing Zhang, Peng Zhang, Yixin Tan, Shuaihantian Luo, Xin Huang, Yaxiong Deng, Wei Liao, Liu Duan, Jianbo Chen, Yin Zhou, Jinghua Yin, Hong Qiu, Jin Yuan, Zijun Wang, Mengying Li, Xiaoqi Wu, Lina Chen, Liangmin Cai, Cancan Huang, Qianwen Li, Bingsi Tang, Bihui Yu, Xin Li, Xiaofei Gao, Yixi Hu, Xiaolei Ren, Haofan Xue, Zhangming Wei, Jinwei Chen, Fen Li, Guanghui Ling, Hui Luo, Hongjun Zhao, Sen Yang, Yong Cui, Youkun Lin, Xu Yao, Lingyun Sun, Qing Guo, Hong Fang, Kang Zeng, Danqi Deng, Jianzhong Zhang, Yuzhen Li, Xiongming Pu, Xiangping Liao, Xiqiang Dang, Danlin Huang, Yumei Liang, Qing Sun, Hongju Xie, Li Zeng, Cibo Huang, Qingchun Diao, Juan Tao, Jianbin Yu, Zhenlu Li, Hanshi Xu, Hui Li, Wei Lai, Xiguang Liu, Jingjing Wu, Tienan Li, Tiechi Lei, Qiuning Sun, Yanjia Li, Guoqiang Zhang, Xin Huang and Qianjin Lu in Lupus

To conduct an in vitro investigation into the effect of different concentrations of levocetirizine hydrochloride on the growth of human dermal papilla cells (hDPCs) the underlying mechanisms involved.hDPCs were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing different concentrations of levocetirizine hydrochloride for 48 h. The growth of hDPCs was observed by immunofluorescence staining, and the cell proliferation was detected by MTT assay. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, and 10,000 ng/mL levocetirizine hydrochloride for 48 h, the mRNA expressions of cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), G protein-coupled receptor 44 (GPR44), protein kinase B (AKT), and glycogen synthase kinase 3β (GSK3β) were determined by real-time fluorescence-based quantitative polymerase chain reaction (PCR), and the protein expressions of PTGDS, phosphorylated protein kinase B (pAKT), and phosphorylated glycogen synthase kinase 3β (pGSK3β) were detected by Western blotting. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, 10,000 ng/mL levocetirizine hydrochloride for 24 h, the secretion levels of prostaglandin D2 (PGD2) and PGD2 receptor (PGD2R) in the culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) was performed using SPSS 17.0 software, and the LSD-t test was used for pairwise comparisons.Immunofluorescence staining showed that hDPCs in the 100 ng/mL group grew well, with over 90% confluency. Methyl thiazolyl tetrazolium (MTT) method showed that the proliferation rate of hDPCs significantly differed between different levocetirizine hydrochloride groups and the blank control group (F=42.22, P0.05), while the proliferation rate was significantly higher in the 100 ng/mL group (115.80%±5.10%) than in the blank control group (100%) (t=28.26, P0.05). The relative mRNA expressions of COX-2, PGF2a, PTGDS, GPR44, and AKT showed significant differences in different levocetirizine hydrochloride groups (the F values were 1.97, 3.66, 2.17, 2.66, and 7.32, respectively; all P0.05), whereas the mRNA expressions of PGE2 and GSK3β showed no significant difference (F=0.87, F=1.19, respectively; both P0.05). The mRNA expressions of COX-2, PTGDS, and GPR44 in the 100 ng/mL group (0.840.08, 0.810.10, and 0.85±0.09, respectively) were significantly lower than those in the blank control group (t=1.97, t=2.17, and t=2.65, respectively; all P0.05), whereas the mRNA expressions of PGF2α and AKT in the 100 ng/mL group (1.96±0.25 and 1.74±0.32, respectively) were significantly higher than those in the blank control group (t=3.662 and t=7.325, respectively; both P0.05). There were significant differences in the levels of PTGDS, pAKT, pGSK3β, PGD2, and PGD2R proteins between the different levocetirizine hydrochloride groups (the F values were 11.84, 3.89, 4.07, 66.15, and 44.33, respectively). The protein expressions of PTGDS, PGD2, and PGD2R in the 100 ng/mL group (0.32±0.05, 141.62±5.44, and 215.08±9.55, respectively) were significantly lower than those in the blank control group (0.73±0.06, 180.08±6.15, and 273.24±3.18, respectively) (the t values were 5.66, 45.07, and 92.05, respectively; all P0.05), whereas the protein expressions of pAKT and pGSK3β in the 100 ng/mL group (0.59±0.05 and 0.46±0.03, respectively) were significantly higher than those in the blank control group (0.46±0.02 and 0.35±0.042, respectively) (t=16.59, t=7.73, respectively; both P0.05).Levocetirizine hydrochloride may promote the growth and proliferation of hDPC in vitro by inhibiting the PGD2-GPR44 pathway and activating the AKT signaling pathway.

Mutations in TIE2/TEK gene have been identified as the major cause for cutaneomucosal venous malformations (VMCM) that were previously reported to occur in Caucasian families. We report here for the first time a Chinese VMCM family of 19 affected individuals in five generations with multiple vascular lesions on their oral mucosa and extremities. Histological analyses showed that the lesions comprised of irregular vascular spaces with a continuous layer of endothelial cells and variable smooth muscle cells. Although these VMCM characters were consistent with those in Caucasian families, difference was observed in hyperplastic SMC layer and vascular walls. Haplotype analyses and DNA sequencing indicated that both the mutation-associated haplotype and a R849W (c.2545C>T) change of the TIE2 gene cosegregated perfectly with the VMCM phenotype. This result suggested that, like those in Caucasian families, the R849W mutation in TIE2 could be one of the major causes for VMCM in Asian families.

Toll-like receptors (TLRs) are pattern-recognition receptors and have a critical role in both innate and adaptive responses to tissue injury. Our previous study showed that wound healing was impaired in TLR3-deficient mice. In this study, we investigated the capacity of the TLR3 agonist polyriboinosinic-polyribocytidylic acid (poly(I:C)) to promote the healing of skin wounds in humans and mice. We found that topical application with poly(I:C) accelerated the closure of wounds in patients with laser plastic surgery. In a mouse model, topical application of poly(I:C) markedly enhanced re-epithelialization, granulation, and neovascularization required for wound closure. Further studies revealed that poly(I:C) treatment resulted in enhanced recruitment of neutrophils and macrophages in association with upregulation of a chemokine, macrophage inflammatory protein-2 (MIP-2/CXCL2), in the wounds. The effect of poly(I:C) was abolished in TLR3-deficient mice or by treatment with MIP-2/CXCL2-neutralizing antibodies. These results suggest a potential therapeutic value of the TLR3 activator poly(I:C) for wound healing.