Translational research : the journal of laboratory and clinical medicine
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Vascularization has a pivotal role in engineering successful tissue constructs. However, it remains a major hurdle of bone tissue engineering, especially in clinical applications for the treatment of large bone defects. Development of vascularized and clinically-relevant engineered bone substitutes with sufficient blood supply capable of maintaining implant viability and supporting subsequent host tissue integration remains a major challenge. ⋯ Numerous applications of engineered vascularization with cell-and/or microfabrication-based approaches seek to meet these aims. Three-dimensional (3D) printing promises to create patient-specific bone constructs in the future. In this review, we discuss the major components of fabricating vascularized 3D bioprinted bone constructs, analyze their related challenges, and highlight promising future trends.
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Our objective was to assess whether volatile organic compound (VOC) analysis of vaginal swabs can detect maternal Group B Streptococcus (GBS) during pregnancy in a prospective exploratory study. Around 243 women attending a high-risk antenatal clinic at one university teaching hospital in the UK consented to take part and provide vaginal swabs throughout pregnancy. VOC analysis of vaginal swabs was undertaken and compared with the reference standard of GBS detected using enrichment culture method. ⋯ Our study has demonstrated that the sensitivity and specificity of the VOC analysis by GC-IMS for the detection of GBS from vaginal swabs was 0.81 (95% confidence interval [CI], 0.71-0.89) and 0.97 (95% CI, 0.91-1) respectively. We conclude that the use of VOCs as biomarkers for the detection of maternal GBS in the vagina is a novel tool. As this test produces results within minutes and is of low unit test cost, it has the potential to be used in clinical settings, where fast diagnosis is important, for example, a patient in early labour.
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Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). CD74 (major histocompatibility complex, class II invariant chain) is the main receptor for MIF. However, the role of the MIF/CD74 axis in atrial arrhythmogenesis is unclear. ⋯ MIF-mediated electrical dysregulation and CaMKII-RyR2 signaling activation were attenuated through blocking of CD74. Moreover, MIF-injected mice had lesser left atrium fractional shortening, greater atrial fibrosis, and atrial ectopic beats than control (nonspecific immunoglobulin treated) or MIF combined with anti-CD74 neutralized antibody-treated mice. Consequently, our study on MIF/CD74 signaling has pointed out a new potential therapeutic intervention of AF patients with MIF elevation.
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Interleukin (IL)-22 activates STAT (signal transducer and activator of transcription) 3 and antiapoptotic and proproliferative pathways; but beyond this, the molecular mechanisms by which IL-22 promotes carcinogenesis are poorly understood. Characterizing the molecular signature of IL-22 in human DLD-1 colon carcinoma cells, we observed increased expression of 26 genes, including NNMT (nicotinamide N-methyltransferase, ≤10-fold) and CEA (carcinoembryonic antigen, ≤7-fold), both known to promote intestinal carcinogenesis. ERP27 (endoplasmic reticulum protein-27, function unknown, ≤5-fold) and the proinflammatory ICAM1 (intercellular adhesion molecule-1, ≤4-fold) were also increased. ⋯ Importantly, augmentation of NNMT was 5-14-fold greater in human cancerous compared to normal organoids, supporting a role for NNMT in IL-22-mediated colon carcinogenesis. Thus, NNMT and CEA emerge as mediators of the tumor-promoting effects of IL-22 in the intestine. These data advance our understanding of the multifaceted role of IL-22 in the gut and suggest the IL-22 pathway may represent a therapeutic target in colon cancer.
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GV1001, a novel peptide derived from human telomerase reverse transcriptase, reportedly has anticancer and anti-inflammatory effects. Choroidal neovascularization (CNV) is a complex pathogenic process that involves angiogenesis, inflammation, cellular immunity, and other factors. This study was aimed at investigating the effect of GV1001 on laser-induced CNV in a rat model. ⋯ At 1 nM concentration, GV1001 had highest inhibitory effect on CNV and NF-κB signaling activation; moreover, it suppressed the levels of IL-1β, IL-6, and VEGF significantly. The present study demonstrates that GV1001 treatment led to significant suppression of laser-induced CNV, alongside inhibition of inflammatory processes including NF-κB activation and subsequent upregulation of proinflammatory cytokines. Therefore, this provides molecular evidence of potential validity of GV1001 treatment as a therapeutic strategy for neovascular age-related macular degeneration.