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3%) patients at baseline and at progression disease (PD), respectively. The expression levels of MCT4 was found to increase in CTCs at the time of relapse. Kaplan-Meier analysis showed that the overexpression of MCT4 was significantly (P = 0.045) associated with progression-free survival (median 12.5 months, range 5-31 months). Conclusion MCT4 overexpression was observed at a high frequency in CTCs from early NSCLC patients supporting its role in metastatic process. MCT4 investigated as clinically relevant tumor biomarker characterizing tumor aggressiveness and its potential value as target for cancer therapy. We are totally convinced that MCT4 overexpression in CTCs merits further evaluation as a non-invasive circulating tumor biomarker in a large and well-defined cohort of patients with NSCLC.As the material transportation system of the human body, the vascular network carries the transportation of materials and nutrients. Currently, the construction of functional microvascular networks is an urgent requirement for the development of regenerative medicine and in vitro drug screening systems. this website How to construct organs with functional blood vessels is the focus and challenge of tissue engineering research. Here in this review article, we first introduced the basic characteristics of blood vessels in the body and the mechanism of angiogenesis in vivo, summarized the current methods of constructing tissue blood vessels in vitro and in vivo, and focused on comparing the functions, applications and advantages of constructing different types of vascular chips to generate blood vessels. Finally, the challenges and opportunities faced by the development of this field were discussed.Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease but the efficacy of current treatment remains unsatisfactory. The pathogenesis of DKD needs a more in-depth research. Ubiquitin specific proteases 36 (USP36), a member of deubiquitinating enzymes family, has aroused wide concerns for its role in deubiquitinating and stabilizing target proteins. Nevertheless, the role of USP36 in diabetes has never been reported yet. Herein, we identified an increased expression of USP36 both in vitro and in vivo in diabetic renal tubular epithelial cells (TECs), and its overexpression is related to the enhanced epithelial-to-mesenchymal transition (EMT). Further investigation into the mechanisms proved that USP36 could directly bind to and mediate the deubiquitination of dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF) that could activate Wnt/β-catenin signaling pathway and induce EMT. Our study revealed a new mechanism that USP36 participates in the pathogenesis of DKD, and provided potential intervening targets accordingly.Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Stem cell transplantation has become a promising approach for the treatment of IHD in recent decades. It is generally recognized that preclinical cell-based therapy is effective and have yielded encouraging results, which involves preventing or reducing myocardial cell death, inhibiting scar formation, promoting angiogenesis, and improving cardiac function. However, clinical studies have not yet achieved a desired outcome, even multiple clinical studies showing paradoxical results. Besides, many fundamental puzzles remain to be resolved, for example, what is the optimal delivery timing and approach? Additionally, limited cell engraftment and survival, challenging cell fate monitoring, and not fully understood functional mechanisms are defined hurdles to clinical translation. Here we review some of the current dilemmas in stem cell-based therapy for IHD, along with our efforts and opinions on these key issues.Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Thus, ALS astrocyte secretome may disrupt cell homeostasis and impact on ALS pathogenesis. Previously, we identified a specific aberrant signature in the cortical brain of symptomatic SOD1-G93A (mSOD1) mice, as well as in astrocytes isolated from the same region of 7-day-old mSOD1 mice, with upregulated S100B/HMGB1/Cx43/vimentin and downregulated GFAP. The presence of downregulated miR-146a on both cases suggests that it can be a promising target for modulation in ALS. Here, we upreg either secretome, or their isolated sEVs. Proteomic analysis of the target cells indicated that pre-miR-146a regulates mitochondria and inflammation via paracrine signaling. We demonstrate that replenishment of miR-146a in mSOD1 cortical astrocytes with pre-miR-146a or by VS abrogates their phenotypic aberrancies and paracrine deleterious consequences to MNs and microglia. These results propose miR-146a as a new causal and emerging therapeutic target for astrocyte pathogenic processes in ALS.NSUN5, encoding a cytosine-5 RNA methyltransferase and located in the 7q11.23 locus, is a candidate gene for tetralogy of Fallot (TOF). Deletion of the 7q11.23 locus in humans is linked to cardiac outflow tract (OFT) disorders including TOF. We identified four potential pathogenic mutations in the coding region of NSUN5 and which were enriched in TOF patients by an association study of 132 TOF patients and 2,000 in-house controls (P = 1.44 × 10-5). We then generated a Nsun5 null (Nsun5 -/-) mouse model to validate the human findings by defining the functions of Nsun5 in OFT morphogenesis. The OFT did not develop properly in the Nsun5 deletion embryonic heart. We found a misalignment of the aorta and septum defects caused by the delayed fusion of the membraneous ventricular spetum as an OFT development delay. This caused OFT development delay in 27 of 64 (42.2%) Nsun5 -/- mice. Moreover, we also found OFT development delay in 8 of 51 (15.7%) Nsun5 +/- mice. Further functional experiments showed that the loss of Nsun5 function impaired the 5-methylcytosine (m5C) modification and translation efficiency of essential cardiac genes.