ABSTRACT
In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.
ABSTRACT
Preventing bacterial infection and improving the osseointegration of titanium (Ti) and its alloys are both highly crucial factors for their long-term successful implantation in clinical applications. However, the straightforward applications of antibacterial surfaces on Ti-based materials remain limited due to their side effects on cytocompatibility. Herein, catechol-functionalized multilayer films composed of dopamine-modified hyaluronic acid (HA-c) and 3,4-dihydroxyhydrocinnamic acid-modified chitosan (Chi-c) were developed on Ti substrates modified with TiO2 nanotube arrays loaded with an antibacterial drug. The treated Ti substrate showed strong hydrophilicity, with a water contact angle of about 20°, and obviously inhibited early-stage bacterial adhesion. Moreover, this system displayed an enzyme-responsive release of antibacterial drug triggered by the hyaluronidase degradation of HA-c, which exhibited effective antibacterial ability and eliminated side effects caused by burst release of antibiotics. Meanwhile, the modified Ti substrates significantly promoted initial osteoblast adhesion through up-regulating the expression of adhesion-related genes, including integrin αv and ß3. More importantly, this prepared coating with bacterial self-responsiveness improved osseointegration and prevented bacterial infection of Ti implants in vivo. Overall, our developed catechol-functionalized and bacterial self-responsive coating on Ti substrate has great significance in clinical applications of orthopedic and dental implants.
