Phycocyanin relieves myocardial ischemia-reperfusion injury in rats by inhibiting oxidative stress

Purpose: To investigate the effect of phycocyanin on myocardial ischemia-reperfusion injury, and the possible mechanisms involved. Methods: Twenty-four Sprague-Dawley (SD) rats were randomly divided into Sham group (only threading without ligation), IRI group (myocardial ischemia-reperfusion injury group) and phycocyanin group (phycocyanin pretreatment + myocardial ischemia-reperfusion injury group). The heart was harvested and cardiomyocytes were isolated. Colorimetry was used to determine the contents of cardiomyocyte serum creatine phospho-MB (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and the activities of total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), total superoxide dismutase (SOD) and other related oxidative stress indicators. Furthermore, apoptosis was evaluated using TUNEL staining. Protein levels of cardiac factor E2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), human NADPH dehydrogenase 1 (NQO1) and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. Results: Compared with the myocardial IRI group, the contents of CK-MB, LDH, MAD and ROS in the treated group were significantly decreased (p < 0.05), but the activities of SOD, GSH, SOD, CAT, and T-AOC in the myocardial tissues were significantly enhanced (p < 0.05). Moreover, the pathological changes in myocardial tissue were significantly reduced. In addition, the expression levels of Nrf2, HO-1 and NQO-1 were significantly up-regulated after phycocyanin pretreatment, while expression of NF-κB was significantly down-regulated (p < 0.05). Conclusion: Phycocyanin improves myocardial anti-oxidative stress via activation of Nrf2 signaling pathway, and also protects rats from myocardial ischemia-reperfusion injury by reducing inflammatory response via inhibition of NF-κB signaling pathway

Shape Stability of Metallic Nanoplates: A Molecular Dynamics Study

Abstract(#br)Metallic nanoplates have attracted widespread interests owing to their functional versatility, which relies heavily on their morphologies. In this study, the shape stability of several metallic nanoplates with body-centered-cubic (bcc) lattices is investigated by employing molecular dynamics simulations. It is found that the nanoplate with (110) surface planes is the most stable compared to the ones with (111) and (001) surfaces, and their shapes evolve with different patterns as the temperature increases. The formation of differently orientated facets is observed in the (001) nanoplates, which leads to the accumulation of shear stress and thus results in the subsequent formation of saddle shape. The associated shape evolution is quantitatively characterized. Further..

Nonlinear Magneto-Electro-Mechanical Response of Physical Cross-Linked Magneto-Electric Polymer Gel

This work reports on a novel magnetorheological polymer gel with carbon nanotubes and carbonyl iron particles mixed into the physical cross-linked polymer gel matrix. The resulting composites show unusual nonlinear magneto-electro-mechanical responses. Because of the low matrix viscosity, effective conductive paths formed by the CNTs were mobile and high-performance sensing characteristics were observed. In particular, due to the transient and mutable physical cross-linked bonds in the polymer gel, the electromechanical behavior acted in a rate-dependent manner. External stimulus at a high rate significantly enhanced the electrical resistance response during mechanical deformation. Meanwhile, the rheological properties were regulated by the external magnetic field when magnetic particles were added. This dual enhancement mechanism further contributes to the active control of electromechanical performance. These polymer composites could be adopted as electromechanical sensitive sensors to measure impact and vibration under different frequencies. There is great potential for this magnetorheological polymer gel in the application of intelligent vibration controls

Individualized prevention of proton pump inhibitor related adverse events by risk stratification

Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public

Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2

Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown. In this study, we generate a structural model of the NUDT9-H domain and identify the binding pocket for ADPR using induced docking and molecular dynamics simulation. We find a subset of 11 residues—H1346, T1347, T1349, L1379, G1389, S1391, E1409, D1431, R1433, L1484, and H1488—that are most likely to directly interact with ADPR. Results from mutagenesis and electrophysiology approaches support the predicted binding mechanism, indicating that ADPR binds tightly to the NUDT9-H domain, and suggest that the most significant interactions are the van der Waals forces with S1391 and L1484, polar solvation interaction with E1409, and electronic interactions (including π–π interactions) with H1346, T1347, Y1349, D1431, and H1488. These findings not only clarify the roles of a range of newly identified residues involved in ADPR binding in the TRPM2 channel, but also reveal the binding pocket for ADPR in the NUDT9-H domain, which should facilitate structure-based drug design for the TRPM2 channel

Development and Validation of an Effective CRISPR/Cas9 Vector for Efficiently Isolating Positive Transformants and Transgene-Free Mutants in a Wide Range of Plant Species

The CRISPR/Cas9 technique is a highly valuable tool in creating new materials for both basic and applied researches. Previously, we succeeded in effectively generating mutations in Brassica napus using an available CRISPR/Cas9 vector pKSE401, while isolation of Cas9-free mutants is laborious and inefficient. Here, we inserted a fluorescence tag (sGFP) driven by the constitutive 35S promoter into pKSE401 to facilitate a visual screen of mutants. This modified vector was named pKSE401G and tested in several dicot plant species, including Arabidopsis, B. napus, Fragaria vesca (strawberry), and Glycine max (soybean). Consequently, GFP-positive plants were readily identified through fluorescence screening in all of these species. Among these GFP-positive plants, the average mutation frequency ranged from 20.4 to 52.5% in Arabidopsis and B. napus with stable transformation, and was 90.0% in strawberry and 75.0% in soybean with transient transformation, indicating that the editing efficiency resembles that of the original vector. Moreover, transgene-free mutants were sufficiently identified in Arabidopsis in the T2 generation and B. napus in the T1 generation based on the absence of GFP fluorescence, and these mutants were stably transmissible to next generation without newly induced mutations. Collectively, pKSE401G provides us an effective tool to readily identify positive primary transformants and transgene-free mutants in later generations in a wide range of dicot plant species

Sirtuin 6 maintains epithelial STAT6 activity to support intestinal tuft cell development and type 2 immunity

Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD+-dependent deacetylases and has established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection