Differential lncRNA profiles of blood plasma-derived exosomes from systemic lupus erythematosus.

INTRODUCTION: Long non-coding RNAs (lncRNAs) dysregulation is key in the pathogenesis of systemic lupus erythematosus (SLE), but the role of exosomal lncRNAs in SLE has not been well studied. We elucidated the profiles of plasma exosomal lncRNAs expression in patients with SLE and predictd their potential clinical significance in SLE. METHODS: In the screening stage, six newly diagnosed and untreated patients with SLE and six healthy controls were examined by high-throughput sequencing technology, and differential exosomal lncRNA profiles were constructed. In the validation phase, two differentially selected exosomal lncRNAs from 20 patients each with active and stable SLE and 20 healthy controls were verified with RT-qPCR. The correlation between the selected exosomal lncRNAs and SLE clinical indicators was examined. The diagnostic value of the selected exosomal lncRNAs in SLE was analyzed by the receiver operator characteristic (ROC) curve. RESULTS: Exosomes were successfully extracted from the patients and controls. Sequencing-phase sequencing demonstrated 528 upregulated lncRNAs and 7491 downregulated lncRNAs. In the validation stage, exosomal LINC00667 and DANCR were significantly upregulated in the patients, and positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Exosomal DANCR expression between the active and stable SLE patients was different. The area under the curve(AUC) of exosomal LINC00667 and DANCR for SLE diagnosis was 0.815 and 0.759, respectively. CONCLUSIONS: Exosomal LINC00667 and DANCR were upregulated in SLE, and might be new biomarkers thereof. Exosomal DANCR was associated with SLE activity.

The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity. METHODS: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity. RESULTS: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively). CONCLUSIONS: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.

From Short- to Long-Range Chiral Recognition on Surfaces: Chiral Assembly and Synthesis.

Research on chiral behaviors of small organic molecules at solid surfaces, including chiral assembly and synthesis, can not only help unravel the origin of the chiral phenomenon in biological/chemical systems but also provide promising strategies to build up unprecedented chiral surfaces or nanoarchitectures with advanced applications in novel nanomaterials/nanodevices. Understanding how molecular chirality is recognized is considered to be a mandatory basis for such studies. In this review, a series of recent studies in chiral assembly and synthesis at well-defined metal surfaces under ultra-high vacuum conditions are outlined. More importantly, the intrinsic mechanisms of chiral recognition are highlighted, including short/long-range chiral recognition in chiral assembly and two main strategies to steer the reaction pathways and modulate selective synthesis of specific chiral products on surfaces.

Highly Selective On-Surface Reactions of Aryl Propiolic Acids via Decarboxylative Coupling.

Aryl propiolic acids are introduced as a new class of monomers in the field of on-surface chemistry to build up poly(arylenebutadiynylenes) through decarboxylative Glaser coupling. As compared to aryl alkynes that are routinely used in the on-surface Glaser coupling, it is found that the decarboxylative coupling occurs at slightly lower temperature and with excellent selectivity. Activation occurs through decarboxylation for the propiolic acids, whereas the classical Glaser coupling is achieved through alkyne CH activation, and this process shows poor selectivity. The efficiency of the decarboxylative coupling is documented by the successful polymerization of bis(propiolic acids) as monomers. It is also found that the new activation mode is compatible with aryl bromide functionalities, which allows the formation of unsymmetric metal-organic polymers on the surface by chemoselective sequential reactions. All transformations are analyzed by a scanning tunneling microscope and are further studied by density functional theory calculations.

Neutrophils in ANCA-associated vasculitis: Mechanisms and implications for management.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic autoimmune diseases, which is typified by inflammatory necrosis predominantly affecting the small vessels and often accompanied by positive ANCA. Clinically, AAV primarily includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). It has been found that in AAV pathogenesis, both innate and adaptive immunity are related to neutrophil function mutually. Many proteins, such as myeloperoxidase (MPO) and proteinase 3 (PR3), in neutrophil cytoplasm lead to the production of proteins such as MPO-ANCA and PR3-ANCA by activating adaptive immunity. In addition, through the process of neutrophil extracellular trap (NET) formation, activation of an alternative complement pathway and the respiratory burst can stimulate the neutrophils close to vascular endothelial cells and will participate the vessel inflammation. This review aims to reveal the potential mechanisms regulating the association between the neutrophils and various types of AAVs and to emphasize the results of recent findings on these interactions. Moreover, multiple underlying signaling pathways involved in the regulation of neutrophils during AAV processes have also been discussed. The ultimate goal of this review is to identify novel biomarkers and therapeutic targets for AAV management in the future.

Modulation on the Iron Centers by Selective Synthesis of Organic Ligands with Stereo-Specific Conformations.

Advanced fabrication of surface metal-organic complexes with specific coordination configuration and metal centers will facilitate to exploit novel nanomaterials with attractive electronic/magnetic properties. The precise on-surface synthesis provides an appealing strategy for in situ construction of complex organic ligands from simple precursors autonomously. In this paper, distinct organic ligands with stereo-specific conformation are separately synthesized through the well-known dehalogenative coupling. More interestingly, the exo-bent ligands promote the mono-iron chelated complexes with the Fe center significantly decoupled from the surface and of high spin, while the endo-bent ligands lead to bi-iron chelated ones instead with ferromagnetic properties.

Ikappa B kinase alpha involvement in the development of nasopharyngeal carcinoma through a NF-κB-independent and ERK-dependent pathway.

OBJECTIVES: Ikappa B kinase alpha (IKKα) plays an inhibitory role in the development of epithelial-derived tumors. However, its specific function in the development of nasopharyngeal carcinoma (NPC) remains unknown. In this study we identify the role and mechanism of IKKα in IKKα-mediated NPC development. MATERIAL AND METHODS: The effect of IKKα on migration, invasion and tumorigenesis of NPC cell lines was determined using in vitro and in vivo studies. SUNE-1-5-8F cells transfected to overexpress IKKα, SUNE-1-6-10B cells with shRNA-mediated knockdown of IKKα, and three NPC cell lines were studied using Western blotting techniques to compare the major molecules in NF-κB pathways. Additionally, the extracellular signal-regulated kinase (ERK) pathway and matrix metalloproteinases (MMPs) in IKKα-regulated NPC and the effect of Epstein-Barr Nuclear Antigen 1 (EBNA1) on IKKα were examined. RESULTS: IKKα was underexpressed in highly invasive SUNE-1-5-8F cells compared with non-invasive cells (SUNE-1 and SUNE-6-10B). Overexpression of IKKα in SUNE-1-5-8F cells was achieved through transfection and resulted in inhibited migration and invasion in vitro. Furthermore, IKKα inhibited tumorigenesis in mice inoculated with IKKα-transfected NPC cells in vivo. These processes were independent of the conventional effect of IKKα on Nuclear factor κB (NF-κB) pathways. The ERK pathway was involved in IKKα-related NPC inhibition. Phosphorylation of ERK1/2 and subsequent secretion of MMP-9 were inhibited by the ERK inhibitor U0126 and not regulated by overexpressed IKKα. EBNA1 knockdown using small interfering RNA (siRNA) did not alter the expression of IKKα. CONCLUSION: Increase in IKKα expression suppresses the progression of NPC through a NF-κB-independent and ERK-dependent pathway.