Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
In a series of Huntington’s disease (HD) brains, the authors identified phospho-tau aggregation in all cases. In contrast to recent observations suggesting a new role for tau in HD pathogenesis, the tau pathology in our cases was classifiable into known diagnostic entities and most likely represents non-specific age- or perhaps trauma-related changes.
Isocitrate dehydrogenase (IDH) mutations can be identified by gas chromatography mass spectrometry (GC/MS). The sensitivity and specificity are 100% in gliomas for the accumulation of 2-hydroxyglutarate (2-HG), whereas the ratio of 2-HG/glutamic acid also serves as a reliable index. The modified mini-column GC/MS method could shorten the procedure to 40 min for rapid diagnosis.
Two in vitro skin-like tissue models were used to recapitulate disease-relevant hallmarks of fibrosis. Anti-fibrogenic phenotypes were achieved upon inhibiting lysyl oxidase enzynes in these tissues. This study points to a pivotal role for lysyl oxidases in fibrosis and shows the value of these tissue-based platforms for discovering new therapeutics.
Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptors (EGFR) (EGFR-TKIs) significantly prolong the survival of lung adenocarcinoma patients with sensitizing EGFR mutations. Unfortunately, 10–30% patients do not show objective responses to EGFR-TKIs, and undergo rapid disease progression. We found that miR-608 and miR-4513 polymorphisms are independent biomarkers to predict lung adenocarcinoma patients’ survival after EGFR-TKI treatment. These miRNAs and polymorphisms provide clinical potential in patient-tailored treatment decision-making.
The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the point of care. This review discusses the clinical feasibility of different miRNA amplification-based assays, from conventional methods to alternative technologies such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling-based, and microfluidic chip-based strategies.
Epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor, is localized in both the nucleus and cytoplasm of cell lines and resected lung adenocarcinomas. In this article, the authors show that cytoplasmic expression of ECT2 is associated with poor outcomes and that positive P-ECT2(T790) staining correlates with cytoplasmic ECT2 expression. Furthermore, cytoplasmic ECT2 expression promotes the malignant progression of lung adenocarcinoma.
Polyploid giant cancer cells (PGCCs) have the properties of cancer stem cells, and cell-cycle-related proteins, including cyclin B1, CDC25B, and CDC25C play an important role in regulating the formation of PGCCs. This study shows that the phosphorylated proteins Chk2, and Aurora-A kinase regulate the expression and subcellular localization of cyclin B1, CDC25B, and CDC25C. The subcellular localization of these cell-cycle-related proteins is associated with pathologic grade and metastasis of tumors in cases of human breast cancer and ovarian cancer.
The authors studied the role of Ca2+ in ASIC1a mediated chondrocytes pyroptosis of AA rats. They demonstrated that H+ in joint fluid activates ASIC1a, which promotes Ca2+ flow into cells. The upregulation of intercellular [Ca2+]i contributes to the expression, aggregation and assembly of the NLRP3 inflammasome, followed by the activation of Caspase-1, which cleaves pro-IL-1β /18 into their biologically active forms, and eventually chondrocytes go to pyroptosis.
The authors evaluated the effect of global deletion of NADPH oxidase 4 (NOX4) on TGF-β-induced fibrosis in mouse skin and lungs. Analysis of C57BL6/J and Nox4 knockout mice skin and lung sections by histopathology, measurement of hydroxyproline content and profibrotic gene expression levels showed that Nox4 deletion abrogated TGF-β1-induced tissue fibrosis.
Chronic obstructive pulmonary disease (COPD) is a common, destructive and pre-malignant airway disease often seen in smokers. We know remarkably little about the underlying driving mechanisms. Scientists have recently made important observations indicating that epithelial to mesenchymal transition (EMT) is central to these pathologies, with heparin-binding EGF-like growth factor as an emerging novel therapeutic target to ameliorate EMT in smokers and patients with COPD.
In this study, the authors found that the transcriptional regulator myocyte enhancer binding factor 2 B (MEF2B) is an essential component of the BCL6 gene transcriptional complex and promotes diffuse large B-cell lymphoma (DLBCL) growth by inducing BCL6 expression. In addition to its regulatory role in DLBCL growth, MEF2B expression correlates positively with BCL6 and CD10 expression, and preferentially expressed in the germinal center B-cell-like DLBCL group.
Krüppel-like factor 2 (KLF2) is expressed in primary osteoblasts and is upregulated during osteoblast differentiation. The authors show that KLF2 promotes osteoblast differentiation and mineralization by increasing expression of the transcription factor Runx2, which is necessary for osteoblast function. Therefore, KLF2 might be a novel therapeutic target for bone disease.
Under hyperglycemic conditions, there is aberrant activation of the Hedgehog pathway due to increased O-GlcNAcylation of the GLI1 and GLI2 transcription factors; this modification enhances their transcriptional activity. This study lays a foundation for inhibiting O-GlcNAcylation, particularly in cancer patients with diabetes or metabolic disease, in order to control metabolism, progression and/or drug resistance of breast cancer.
The trigeminal sensory nerve is critical for maintenance of corneal epithelial stem cells in the corneal limbus and is essential to the homeostasis of the tissue. TRPV4 signal mediated gene expression in the nerve drives expression of stem cell markers and nerve growth factor in the limbal stem cells as well as potentiates their proliferation.
High expression of the transcription factor ZNF326 correlates with low differentiation and high pTNM stage of non-small cell lung cancer (NSCLC) cells. ZNF326 promotes proliferation, invasion, and tumorigenesis of NSCLC cells in vivo and in vitro. ZNF326 directly targets ERCC1, a DNA excision repair protein, binding to its promoter region, thereby promoting cyclinB1 synthesis and cell cycle progression.
Tetraspanin CD9 is essential for sperm–egg fusion and contributes to uterine repair through microexosome formation. In the present study, we report that CD9 repositioning and release affect both membrane structures and mitochondrial state in the uterine epithelium, and contribute to female fertility.