Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

Comparing hydroxyapatite with osteogenic medium for the osteogenic differentiation of mesenchymal stem cells on PHBV nanofibrous scaffolds.

Having advantageous biocompatibility and osteoconductive properties known to enhance the osteogenic differentiation of mesenchymal stem cells (MSCs), hydroxyapatite (HA) is a commonly used material for bone tissue engineering. What remains unclear, however, is whether HA holds a similar potential for stimulating the osteogenic differentiation of MSCs to that of a more frequently used osteogenic-inducing medium (OIM). To that end, we used PHBV electrospun nanofibrous scaffolds to directly compare the osteogenic capacities of HA with OIM over MSCs. Through the observation of cellular morphology, the staining of osteogenic markers, and the quantitative measuring of osteogenic-related genes, as well as microRNA analyses, we not only found that HA was as capable as OIM for differentiating MSCs down an osteogenic lineage; albeit, at a significantly slower rate, but also that numerous microRNAs are involved in the osteogenic differentiation of MSCs through multiple pathways involving the inhibition of cellular proliferation and stemness, chondrogenesis and adipogenesis, and the active promotion of osteogenesis. Taken together, we have shown for the first time that PHBV electrospun nanofibrous scaffolds combined with HA have a similar osteogenic-inducing potential as OIM and may therefore be used as a viable replacement for OIM for alternative in vivo-mimicking bone tissue engineering applications.

Synergistic effects of polymer adsorbents on the performance of bilirubin hemoperfusion.

Neonatal hyperbilirubinemia (jaundice) is a common disease with high incidence. Currently, the clinical inefficiency of adult bilirubin hemoperfusion medical adsorbent is a major technical barrier for the application of hemoperfusion treatment to rescue the severe neonatal jaundice. Based on the well-known principle of synergistic effects, a series of customized bilirubin polymeric compounds, comprised of one or more of the following components (glycidyl methacrylate, sodium acrylate, methacrylic acid isooctyl, hexamethylene diamine, albumin), were designed and fabricated based on molecular design. Their adsorption performances upon bilirubin were investigated and compared under the same conditions, and the compound with the highest adsorption performance was then subject to preliliminary safety assessments and compared with a commercial one (BS330). The results showed that positive synergistic effects appeared on the adsorption performance to adsorb bilirubin based on this study, and the one comprised of glycidyl methacrylate+sodium acrylate+methacrylic acid isoocty+hexamethylene diamine+albumin possesses the highest adsorption performance as well as outome clinical acceptable medical safety assessments, and its adsorption efficiency was up to 46% while the commerical one's was about 26% under the same conditions. This study sheds a new light on how to design and develop hemoperfusion bilirubin adsorbents with good overall clinical performance, as well as providing a novel idea and experimental referrences for future related topics.