No abstract

Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3. Prolonged Hcy treatment also upregulated glucose-regulated protein 78 (GRP78), activated protein kinase RNA-like ER kinase (PERK), and induced the expression of C/EBP homologous protein (CHOP) and the phosphorylation of NF-κb. The inhibition of NOX4 decreased the production of ROS and alleviated the Hcy-induced HUVEC apoptosis and ER stress. Blocking the PERK pathway partly alleviated Hcy-induced HUVEC apoptosis and the activation of NF-κb. Taken together, our results suggest that Hcy-induced mitochondrial dysfunction crucially modulated apoptosis and contributed to the activation of ER stress in HUVEC. The excessive activation of the PERK pathway partly contributed to Hcy-induced HUVEC apoptosis and the phosphorylation of NF-κb.

Appropriate deciphering and translation of sequence-dependent function inproteins is inspired by the cation-π interaction that is increasingly implicated in marine adhesives and membraneless organelles. A simplified cation-methylene-phenyl (C-M-P) sequence which enables triggerable poly(ionic liquid) coacervation is reported for the first time. Synthesis of the C-M-P structure motif requires only a one-step quaternization, which is facile compared to the linear sequence of distinct repeating units in model proteins and sequencecontrolled polymers. The C-M-P code confers modular coacervation and advanced wet adhesion to task-specific copolymers. It allows for exceptional underwater adhesion to various submerged substrates including glass (≈1 MPa) and porcine skins (140 KPa), paving the way for prospective adhesive applications in physiological saline and underwater marine salvage. This work introduces a powerful code that, in addition to combining the advantageous adaptive adhesive and phase properties of proteins, reduces the complexity in sequence design for programmable coacervates.

Bioinspired wet adhesives have demonstrated versatile applicability in humid conditions, but the attainment of catecholic protein mimics comprises multistep synthesis and use of complex chemical components. Advanced wet adhesives derived from inexpensive bioresources and green processing are highly expected. We report a straightforward means to underwater-implemented adhesives from aqueous mixing of lignosulfonate (LS) and a polyamidoamineepichlorohydrin (PAE-Cl) solution. The formation of a fluidic LS-PAE complex was driven by a delicate balance between electrostatic attraction and hydrophilic stabilization. The obtained adhesive highlights instant wet adhesion on diverse submerged surfaces and spontaneous curing in water. More importantly, it demonstrates robust and stable bonding strength over the alkali, salty, high-temperature, and long-time soaking conditions. This work advanced the development of lignin into functional wet adhesives through a green and sustainable approach.

No abstract

Counterion exchange of charged macromolecules has comprehensive implications in biological and synthetic systems such as protein function, biosignaling, ion conducting, and separation, but the correlation between the dynamic ion exchange, polyelectrolyte phase separation, and functionality remains elusive. Here, counterion exchange is exploited as a means to facilitate liquid–liquid phase separation and coacervates featuring higher stability and versatility compared with conventional complex coacervate. Self‐coacervation of a cationic polyelectrolyte (polyamidoamine‐epichlorohydrin, PAE‐Cl) occurs in broader conditions when its original counter anion (Cl−) is exchanged by bis(trifluoromethane‐sulphonyl)imide anion (TFSI−), as a result of TFSI− counter anions association instead of polyelectrolyte complexation. This coacervate is catechol‐free, easy to prepare, and highlights robust wet adhesion strength on diverse submerged surfaces in salty water (pH = 3–11), as demonstrated by its versatile capability of in situ underwater gluing and repairing without any pre‐immersive drying.

Injectable hydrogels have recently emerged as alternatives to sutures for various clinical indications. However, existing injectable hydrogels are unsuitable for hemostasis in minimally invasive surgery because of their weak interfacial adhesion and complex/prolonged processing. Herein, a superwetting injectable hydrogel composed of oppositely charged polysaccharides is developed. The spontaneous spreading of the injectable hydrogel on the surfaces achieves complete wetting and forms tight interfacial contact by absorbing the interfacial water. The superwetting ability and subsequent covalent crosslinking perform fast and ultrastrong wet adhesion (140 kPa) on the tissue surface. Ex vivo porcine and in vivo rat models show that the hydrogel successfully leads to the aggregation of erythrocytes for targeted hemostasis (in less than 12 s) without requiring external adjuncts, and no postsurgical adhesions to the peripheral tissues. This further demonstrates that hydrogel can act as an effective hemostasis agent in laparoscopic surgery in a rabbit model. Overall, the strong wet adhesion, antibacterial properties, and easy operability make this injectable hydrogel a promising candidate for hemostasis applications, as it can successfully combine clinical efficacy and transformation opportunities for minimally invasive surgery.

Background Our previous study indicated that Ginkgo biloba leaf extract (EGb) could protect against cisplatin-induced acute kidney injury in rabbits. The present study aimed to determine the effects and potential molecular mechanisms of EGb on chronic renal interstitial fibrosis induced by cisplatin using in vivo and in vitro models. Methods Rats received a single dose of cisplatin on Day 1, and a subset of rats was intraperitoneally injected with EGb daily between Days 22–40. In vitro, HK-2 cells were treated with cisplatin, and a subset of cells was cultivated with EGb or SIS3 (Smad3 inhibitor) for 48 h. Renal function of rats was assessed by detecting the levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG). Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the damage and fibrosis of renal tissue. Western blotting, immunohistochemistry and immunofluorescence were used to detect the protein levels of fibrosis-associated proteins and signaling pathway-related proteins. RT–qPCR analysis was used to examine the mRNA levels of related indicators. Results EGb significantly decreased the increased levels of Scr, BUN and urinary NAG and attenuated renal damage and the relative area of renal interstitial fibrosis induced by cisplatin. Additionally, EGb decreased the protein levels of α-SMA, Col I, TGF-β1, smad2/3, phosphorylated (p)-smad2/3, p38 MAPK, and p-p38 MAPK; the ratio of p-p38 MAPK/p38 MAPK; and the mRNA level of p38 MAPK in renal tissues induced by cisplatin. In agreement with in vivo studies, EGb significantly reduced the increased protein levels of these indicators. Additionally, EGb significantly reduced the increased protein levels of vimentin, TIMP-1, and CTGF, as well as the mRNA levels of α-SMA, vimentin, and TGF-β1, while it significantly increased the reduced E-cadherin protein level and the MMP-1/TIMP-1 ratio in HK-2 cells induced by cisplatin. It’s worth noting that the effects of SIS3 in changing the above indicators were similar to those of EGb. Conclusion Our study demonstrated that EGb improved cisplatin-induced chronic renal interstitial fibrosis, and its mechanisms were associated with inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells via the Smad3/TGF-β1 and Smad3/p38 MAPK pathways.