In recent years, neutrophil extracellular traps at the forefront of neutrophil biology have proven to help capture and kill pathogens involved in the inflammatory process. There is growing evidence that persistent neutrophil extracellular traps drive the pathogenesis of autoimmune diseases. In this paper, we summarize the potential of neutrophil extracellular traps to drive the pathogenesis of rheumatoid arthritis and experimental animal models. We also describe the diagnosis and treatment of rheumatoid arthritis in association with neutrophil extracellular traps.

BackgroundInterleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism.MethodsThe expression pattern and the immune-regulatory role of miR-302b were evaluated both in vitro and in vivo. The functional targets of miR-302b were predicted by bioinformatics, and then validated by genetic approaches. In addition, the clinical feature of miR-302b was analyzed using serum samples of patients with gouty arthritis.ResultsThe extremely high expression of miR-302b was observed in both macrophages and mouse air membranes treated with MSU. Intriguingly, overexpression of miR-302b regulated NF-κB and caspase-1 signaling, leading to significantly attenuate MSU-induced IL-1β. By genetic analysis, miR-302b exhibited inhibitory function on IRAK4 and EphA2 by binding to their 3′-UTR regions. Corporately silencing IRAK4 and EphA2 largely impaired MSU-induced IL-1β protein production. Moreover, it was also found that miR-302b and EphA2 suppressed the migration of macrophages. Finally, it was observed that high expression of miR-302b was a general feature in patients with gouty arthritis.ConclusionsThese results suggest that miR-302b can regulate IL-1β production in MSU-induced inflammation by targeting NF-κB and caspase-1 signaling, and may be a potential therapeutic target for gouty arthritis.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1528-9) contains supplementary material, which is available to authorized users.

PurposeTo assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level.MethodsPenile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB.ResultsDisease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED.ConclusionsOur study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.

Objective In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. Methods We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. Results Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09–1.26, P = 2.51E−05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48–0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36–0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001–1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. Conclusion This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

From a dataset of macrobenthos obtained from 18 cruises from 2004 to 2013 in the Huanghe (Yellow River) Estuary and its adjacent areas, the composition and characteristics of macrobenthos were analyzed, and the applicability of the Shannon-Wiener Index (H′), AZTI's Marine Biotic Index (AMBI) and multivariate AMBI (M-AMBI) for assessing benthic habitat quality was compared. The results showed a total of 203 macrobenthos in the study area. The macrobenthos were dominated by polychaetes, followed by mollusks and crustaceans. The macrobenthic ecological groups were dominated by EGI, EGII and EGIII, which respectively accounted for 31.5%, 36.0% and 21.2% of the total. There were significant differences between the evaluation results of the three indices. The ecological quality status (EQS) levels given by the AMBI were greater than those given by the H′ and M-AMBI. The AMBI could not reflect the differences between 11 sites but the H′ and M-AMBI could do. Moreover, the three indices responded well to the variations in salinity (S) and dissolved oxygen (DO) in the waters. The H′ and M-AMBI also responded sensitively to the differences in physical parameters, such as water depth and sediment texture. The correlation between M-AMBI and environmental pressure gradient data was the strongest. The M-AMBI could effectively distinguish degraded conditions from undegraded but the H′ and AMBI could not. Therefore, the M-AMBI reflected benthic habitat health well in the study areas. However, the objectivity of evaluation results of M-AMBI needs further verification by physical, chemical and biological methods. The thresholds also need further discussion.Citation: Luo Xianxiang, Sun Kaijing, Yang Jianqiang, Song Wenpeng, Cui Wenlin. 2016. A comparison of the applicability of the ShannonWiener index, AMBI and M-AMBI indices for assessing benthic habitat health in the Huanghe (Yellow River) Estuary and adjacent areas.

Bovine milk-derived extracellular vesicles (BM-EVs) are recognized as promising nanoscale delivery vectors owing to their large availability. However, few isolation methods can achieve high purity and yield simultaneously. Therefore, we developed a novel and cost-effective procedure to separate BM-EVs via “salting-out.” First, BM-EVs were isolated from skimmed milk using ammonium sulfate. The majority of BM-EVs were precipitated between 30 and 40% saturation and 34% had a relatively augmented purity. The separated BM-EVs showed a spherical shape with a diameter of 60–150 nm and expressed the marker proteins CD63, TSG101, and Hsp70. The purity and yield were comparable to the BM-EVs isolated via ultracentrifugation while ExoQuick failed to separate a relatively pure fraction of BM-EVs. The uptake of BM-EVs into endothelial cells was dose- and time-dependent without significant cytotoxicity. The levels of endothelial nitric oxide syntheses were regulated by BM-EVs loaded with icariside II and miRNA-155-5p, suggesting their functions as delivery vehicles. These findings have demonstrated that it is an efficient procedure to isolate BM-EVs via “salting-out,” holding great promise toward therapeutic applications.

Objectives. The aim of this study is to explore the textural features that may identify the morphological changes in the lymphoma region and predict the prognosis of patients with primary renal lymphoma (PRL) and primary adrenal lymphoma (PAL). Methods. This retrospective study comprised nineteen non-Hodgkin’s lymphoma (NHL) patients undergoing 18F-FDG-PET/CT at West China Hospital from December 2013 to May 2017. 18F-FDG-PET images were reviewed independently by two board certificated radiologists of nuclear medicine, and the texture features were extracted from LifeX packages. The prognostic value of PET FDG-uptake parameters, patients’ baseline characteristics, and textural parameters were analyzed using Kaplan–Meier analysis. Cox regression analysis was used to identify the independent prognostic factors among the imaging and clinical features. Results. The overall survival of included patients was 18.84 ± 13.40 (mean ± SD) months. Univariate Cox analyses found that the tumor stage, GLCM (gray-level co-occurrence matrix) entropy, GLZLM_GLNU (gray-level nonuniformity), and GLZLM_ZLNU (zone length nonuniformity), values were significant predictors for OS. Among them, GLRLM_RLNU ≥216.6 demonstrated association with worse OS at multivariate analysis (HR 9.016, 95% CI 1.041–78.112, p=0.046). Conclusions. The texture analysis of 18F-FDG-PET images could potentially serve as a noninvasive strategy to predict the overall survival of patients with PRL and PAL.