Limb Ischemic Postconditioning Alleviates Postcardiac Arrest Syndrome through the Inhibition of Mitochondrial Permeability Transition Pore Opening in a Porcine Model

Objective. Previously, the opening of mitochondrial permeability transition pore (mPTP) was confirmed to play a key role in the pathophysiology of postcardiac arrest syndrome (PCAS). Recently, we demonstrated that limb ischemic postconditioning (LIpostC) alleviated cardiac and cerebral injuries after cardiac arrest and resuscitation. In this study, we investigated whether LIpostC would alleviate the severity of PCAS through inhibiting mPTP opening. Methods. Twenty-four male domestic pigs weighing 37±2 kg were randomly divided into three groups: control, LIpostC, and LIpostC+atractyloside (Atr, the mPTP opener). Atr (10 mg/kg) was intravenously injected 30 mins prior to the induction of cardiac arrest. The animals were subjected to 10 mins of untreated ventricular fibrillation and 5 mins of cardiopulmonary resuscitation. Coincident with the beginning of cardiopulmonary resuscitation, LIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results. After resuscitation, systemic inflammation and multiple organ injuries were observed in all resuscitated animals. However, postresuscitation systemic inflammation was significantly milder in the LIpostC group than in the control group. Myocardial, lung, and brain injuries after resuscitation were significantly improved in the LIpostC group compared to the control group. Nevertheless, pretreatment with Atr abolished all the protective effects induced by LIpostC. Conclusion. LIpostC significantly alleviated the severity of PCAS, in which the protective mechanism was associated with the inhibition of mPTP opening

Conjugation of Basic Fibroblast Growth Factor on a Heparin Gradient for Regulating the Migration of Different Types of Cells

Regulation of cell migration by cell growth factors is critical in tissue regeneration such as angiogenesis, wound healing, and bone formation. In this work, basic fibroblast growth factor (bFGF) with a density varying between 0 and 295 ng/cm² was conjugated on heparinized glass slides. The amount of conjugated bFGF was determined by immunofluorescent staining. The mobility of vascular smooth muscle cells (VSMCs) was largely dominated by the bFGF density, whereas that of mesenchymal stem cells (MSCs) and endothelial cells (ECs) was slightly influenced. The migration rate of VSMCs increased initially and then decreased along with the increase of bFGF density. The fastest rate (∼22 μm/h) was found on the bFGF surface with a density of 83 ng/cm². The intrinsic mechanisms of the diverse migration behaviors of the VSMCs, MSCs, and ECs were revealed by studying the expression of bFGF receptors and migration-related proteins. The results show that the cell mobility is regulated by complex and synergetic intracellular signals in a cell type-dependent manner

Correction: Gao et al. TGF-β1 Facilitates TAp63α Protein Lysosomal Degradation to Promote Pancreatic Cancer Cell Migration. <i>Biology</i> 2021, <i>10</i>, 597

In the original publication [...

Solvent-Directed Assembly of a Pyridinium-Tailored Methyl Oleanolate Amphiphile: Stepwise Growth of Microrods and Nanofibers

Although a few architectures have been fabricated by the self-assembly of natural triterpenoids, the precise control of shape and size is rarely studied. Herein, a methyl oleanolate-bearing amphiphile, 1-[2-(methyl oleanolate)-2-oxoethyl]­pyridinium bromide (<b>MOP</b>), has been designed and its assembly behavior was investigated. It was found that the morphologies of <b>MOP</b> assemblies ranged from nanoparticles to rigid microrods and flexible nanofibers in chloroform/<i>p-</i>xylene and methanol/water, respectively. During the assembly process, the systematical variational solvophobic/solvophilic effect resulted in the formation of spherical nanoparticles with opposite dipoles and converse bilayer structures. Moreover, such opposite molecular orientations lead to the inversion of supramolecular chirality and distinct mechanical properties. The driving forces and packing patterns of <b>MOP</b> in each solvent system were clearly demonstrated by the combination of NMR, UV–vis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), theoretical computation, and contact angle experiments, which revealed the roles of triterpenoids and pyridinium cations in the assembly process. This work provides a facile strategy to control the supramolecular structures in triterpenoid-based assemblies by adjusting the solvent polarity and composition

TGF-β1 Facilitates TAp63α Protein Lysosomal Degradation to Promote Pancreatic Cancer Cell Migration

TGF-β signaling plays a pivotal role in promoting tumor cell migration and cancer metastasis. ΔNp63α and TAp63α are two major isoforms of p53-related p63 protein. Our recent study has shown that TGF-β1 promotes ΔNp63α protein degradation to facilitate cancer metastasis. However, whether TAp63α is involved in TGF-β1-induced cancer metastasis remains unclear. In this study, we show that, in human pancreatic cancer MIA PaCa-2 cells harboring p53-R248W allele, TGF-β1 can significantly inhibit TAp63α protein stability in a Smad pathway-independent manner. Lysosome inhibitor, chloroquine, but not proteasome inhibitor MG132, can rescue TGF-β1-induced downregulation of TAp63α protein. In addition, we show that either TGF-β1 treatment or silencing of TAp63α can dramatically increase migration of MIA PaCa-2 cells. Importantly, the restored expression of TAp63α can effectively block TGF-β1-induced migration of MIA PaCa-2 cells. Mechanistically, we show that TGF-β1 promotes TAp63α protein degradation, leading to upregulation of p53-R248W protein expression, and consequently resulting in elevated MIA PaCa-2 cell migration. Together, this study indicates that lysosomal degradation is an important way for regulating TAp63α protein fate and highlights that TGF-β1-TAp63α-mutant p53 axis is critically important in pancreatic cancer metastasis

Modulating the Structure and Properties of Poly(sodium 4-styrenesulfonate)/Poly(diallyldimethylammonium chloride) Multilayers with Concentrated Salt Solutions

Poly(sodium 4-styrenesulfonate) (PSS)/poly(diallyldimethylammonium chloride) (PDADMAC) multilayers were treated with 1–5 M NaCl solutions, resulting in continuous changes in the physicochemical properties of the multilayers. Significant mass loss was observed when the salt concentration was higher than 2 M and reached as high as 72% in a 5 M NaCl solution. The disassembly occurred initially in the superficial layers and then developed in the bulk multilayers. For the multilayers with PDADMAC as the outmost layer, the molar ratio of PSS/PDADMAC was increased and the surface chemistry was changed from PDADMAC domination below 2 M NaCl to PSS domination above 3 M NaCl. Owing to the higher concentrations of uncompensated for polyelectrolytes at both lower and higher salt concentrations, the swelling ratio of the multilayers was decreased until reaching 3 M NaCl and then was increased significantly again. The salt-treated PSS/PDADMAC thin films are expected to show different behaviors in terms of the physical adsorption of various functional substances, cell adhesion and proliferation, and chemical reaction activity

Nanofibrous Dressing with Nanocomposite Monoporous Microspheres for Chemodynamic Antibacterial Therapy and Wound Healing

The excessive use of antibiotics and consequent bacterial resistance have emerged as crucial public safety challenges for humanity. As a promising antibacterial treatment, using reactive oxygen species (ROS) can effectively address this problem and has the advantages of being highly efficient and having low toxicity. Herein, electrospinning and electrospraying were employed to fabricate magnesium oxide (MgO)-based nanoparticle composited polycaprolactone (PCL) nanofibrous dressings for the chemodynamic treatment of bacteria-infected wounds. By utilizing electrospraying, erythrocyte-like monoporous PCL microspheres incorporating silver (Ag)- and copper (Cu)-doped MgO nanoparticles were generated, and the unique microsphere-filament structure enabled efficient anchoring on nanofibers. The composite dressings produced high levels of ROS, as confirmed by the 2,7-dichloriflurescin fluorescent probe. The sustained generation of ROS resulted in efficient glutathione oxidation and a remarkable bacterial killing rate of approximately 99% against Staphylococcus aureus (S. aureus). These dressings were found to be effective at treating externally infected wounds. The unique properties of these composite nanofibrous dressings suggest great potential for their use in the medical treatment of bacteria-infected injuries