Peptidomics Analysis Reveals Peptide PDCryab1 Inhibits Doxorubicin-Induced Cardiotoxicity

Doxorubicin (DOX) is limited due to dose-dependent cardiotoxicity. Peptidomics is an emerging field of proteomics that has attracted much attention because it can be used to study the composition and content of endogenous peptides in various organisms. Endogenous peptides participate in various biological processes and are important sources of candidates for drug development. To explore peptide changes related to DOX-induced cardiotoxicity and to find peptides with cardioprotective function, we compared the expression profiles of peptides in the hearts of DOX-treated and control mice by mass spectrometry. The results showed that 236 differential peptides were identified upon DOX treatment, of which 22 were upregulated and 214 were downregulated. Next, we predicted that 31 peptides may have cardioprotective function by conducting bioinformatics analysis on the domains of each precursor protein, the predicted score of peptide biological activity, and the correlation of each peptide with cardiac events. Finally, we verified that a peptide (SPFYLRPPSF) from Cryab can inhibit cardiomyocyte apoptosis, reduce the production of reactive oxygen species, improve cardiac function, and ameliorate myocardial fibrosis in vitro and vivo. In conclusion, our results showed that the expression profiles of peptides in cardiac tissue change significantly upon DOX treatment and that these differentially expressed peptides have potential cardioprotective functions. Our study suggests a new direction for the treatment of DOX-induced cardiotoxicity

PET-RAFT as a facile strategy for preparing functional lipid-polymer conjugates

From readily available starting materials, we report a facile synthesis of lipid–polymer conjugates (LPCs). Easy access to multigram quantities of a dialkyl lipid chain transfer agent allows a range of LPCs to be prepared bearing well-defined hydrophilic polymer head-groups, controlled molecular weights and low dispersity by photoelectron transfer RAFT polymerization (PET-RAFT). As dictated by the lipid packing parameters, the resulting LPCs were suitable for solution-phase self-assembly, both independently and in combination with naturally occurring phospholipids, affording micelles, smaller vesicle-like structures, or stabilized large unilamellar vesicles. Notably, co-assembly of LPCs and phospholipids bearing mutually orthogonal fluorophores showed negligible phase separation/aggregation. To demonstrate the versatility of these LPCs, the RAFT chain-end was removed, affording thiol-terminated LPCs that could be used for the manipulation and stabilization of gold nanoparticle assemblies. Facile access to structurally diverse LPC building blocks enables a variety of biotechnology and biomedical applications, including drug-delivery, cell engineering, and 3D-printed biomaterials

Imaging antiferromagnetic domains in nickel oxide thin films by optical birefringence effect

Recent demonstrations of electrical detection and manipulation of antiferromagnets (AFMs) have opened new opportunities toward robust and ultrafast spintronics devices. However, it is difficult to establish the connection between the spin-transport behavior and the microscopic AFM domain states in thin films due to the lack of a real-time imaging technique under the electric field. Here we report a large magneto-optical birefringence effect with polarization rotation up to 60 millidegrees in thin NiO(001) films at room temperature. Such large optical polarization rotation allows us to directly observe AFM domains in thin-film NiO by utilizing a wide-field optical microscope. Complementary x-ray magnetic linear dichroism-photoemission electron microscopy measurement further confirms that the optical contrast is related to the NiO AFM domain. We examine the domain pattern evolution at a wide range of temperatures and with the application of external magnetic field. Comparing to large-scale-facility techniques such as x-ray photoemission electron microscopy, using a wide-field, tabletop optical imaging method in reflection geometry enables straightforward access to domain configurations of single-layer AFMs

VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease and proteinuria is one of the most prominent clinical manifestations. The expression of Vitamin D receptor (VDR) in patients with chronic kidney diseases was decreased, while VDR agonists could partially alleviate the proteinuria of DN in animal models. The present study was designed to determine the expression of VDR in renal tissues and its relationship with proteinuria the diabetic model db/db mice. Methods: The regulation effects of VDR on the Wnt signaling pathway were analyzed using RNA interference and VDR agonist paricalcitol. Results: With the increase in age of the db/db mice, the VDR protein and mRNA levels in renal tissues were decreased, proteinuria increased, and the protein and mRNA levels of GSK-3β of and β-catenin increased. Paricalcitol treatment resulted in the up-regulation of VDR and down-regulation of GSK-3β and β-catenin, indicating that VDR had a regulatory effect on the Wnt signaling pathway. Conclusion: VDR activation could reduce proteinuria of DN mice and alleviate high-glucose-induced injury of kidneys and podocytes by regulating the key molecules of Wnt signaling pathway

Altered DNA Methylation of Long Noncoding RNA uc.167 Inhibits Cell Differentiation in Heart Development

In previous studies, we have demonstrated the function of uc.167 in the heart development. DNA methylation plays a crucial role in regulating the expression of developmental genes during embryonic development. In this study, the methylomic landscape was investigated in order to identify the DNA methylation alterations. Methylated DNA immunoprecipitation (MeDIP) was performed to examine the differences in methylation status of overexpressed uc.167 in P19 cells. GO and KEGG pathway analyses of differentially methylated genes were also conducted. We found that the distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in intergenic regions and intron. The biological process associated with uc.167 was focal adhesion and Rap1 signaling pathway. MEF2C was significantly decreased in uc.167 overexpressed group, suggesting that uc.167 may influence the P19 differentiation through MEF2C reduction. Taken together, our findings revealed that the effect of uc.167 on P19 differentiation may be attributed to the altered methylation of specific genes