Heat Shock Protein 70 Protects the Heart from Ischemia/Reperfusion Injury through Inhibition of p38 MAPK Signaling.

BackgroundHeat shock protein 70 (Hsp70) has been shown to exert cardioprotection. Intracellular calcium ([Ca2+]i) overload induced by p38 mitogen-activated protein kinase (p38 MAPK) activation contributes to cardiac ischemia/reperfusion (I/R) injury. However, whether Hsp70 interacts with p38 MAPK signaling is unclear. Therefore, this study investigated the regulation of p38 MAPK by Hsp70 in I/R-induced cardiac injury.MethodsNeonatal rat cardiomyocytes were subjected to oxygen-glucose deprivation for 6 h followed by 2 h reoxygenation (OGD/R), and rats underwent left anterior artery ligation for 30 min followed by 30 min of reperfusion. The p38 MAPK inhibitor (SB203580), Hsp70 inhibitor (Quercetin), and Hsp70 short hairpin RNA (shRNA) were used prior to OGD/R or I/R. Cell viability, lactate dehydrogenase (LDH) release, serum cardiac troponin I (cTnI), [Ca2+]i levels, cell apoptosis, myocardial infarct size, mRNA level of IL-1β and IL-6, and protein expression of Hsp70, phosphorylated p38 MAPK (p-p38 MAPK), sarcoplasmic/endoplasmic reticulum Ca2+-ATPase2 (SERCA2), phosphorylated signal transducer and activator of transcription3 (p-STAT3), and cleaved caspase3 were assessed.ResultsPretreatment with a p38 MAPK inhibitor, SB203580, significantly attenuated OGD/R-induced cell injury or I/R-induced myocardial injury, as evidenced by improved cell viability and lower LDH release, resulted in lower serum cTnI and myocardial infarct size, alleviation of [Ca2+]i overload and cell apoptosis, inhibition of IL-1β and IL-6, and modulation of protein expressions of p-p38 MAPK, SERCA2, p-STAT3, and cleaved-caspase3. Knockdown of Hsp70 by shRNA exacerbated OGD/R-induced cell injury, which was effectively abolished by SB203580. Moreover, inhibition of Hsp70 by quercetin enhanced I/R-induced myocardial injury, while SB203580 pretreatment reversed the harmful effects caused by quercetin.ConclusionsInhibition of Hsp70 aggravates [Ca2+]i overload, inflammation, and apoptosis through regulating p38 MAPK signaling during cardiac I/R injury, which may help provide novel insight into cardioprotective strategies

{μ-6,6′-Dieth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolato}trinitratoholmium(III)nickel(II)

In the title heteronuclear NiII–HoIII complex (systematic name: {μ-6,6′-dieth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolato-1κ4 O 1,O 1′,O 6,O 6′:2κ4 O 1,N,N′,O 1′}trinitrato-1κ6 O,O′-holmium(III)nickel(II)), [HoNi(C20H22N2O4)(NO3)3], with the hexa­dentate Schiff base compartmental ligand N,N′-bis­(3-ethoxy­salicyl­idene)ethyl­enediamine (H2 L), the Ho and Ni atoms are doubly bridged by two phenolate O atoms of the Schiff base ligand. The coordination of Ni is square-planar with the donor centers of two imine N atoms and two phenolate O atoms. The holmium(III) center has a tenfold ­coordination environment of O atoms, involving the phenolate O atoms, two eth­oxy O atoms and two O atoms each from the three nitrates. Weak C—H⋯O and O⋯Ni [3.383 (4) Å] inter­actions generate a two-dimensional zigzag sheet

Surface modification of NiCo2Te4 nanoclusters: a highly efficient electrocatalyst for overall water-splitting in neutral solution

In this paper, we for the first time report the catalytic activity and durability of nickel cobaltite telluride (NiCo2Te4) nanocluster bifunctional catalysts can be significantly boosted by surface modification with perylene-tetracarboxylic-dianhydride for overall water-splitting in neutral solution. We reveal that tuning energy distribution of nanoclusters via a simple surface ligand can drastically increase the catalytic activity towards efficient hydrogen and oxygen evolution reaction simultaneously. A two-electrode based water electrolysis cell using this newly developed nanocluster catalyst operates at a low bias voltage of 1.55 V to achieve a current density of 10 mA·cm-2 in near-neutral pH solution for overall water-splitting. This, to the best of our knowledge, represents the most efficient mixed-transition-metal-based electrode that has so far been reported for electrochemical water splitting

Reduction in interhemispheric functional connectivity in the dorsal visual pathway in unilateral acute open globe injury patients: a resting-state fMRI study

This study investigated the changes in interhemispheric functional connectivity (FC) of the whole brain in open globe injury (OGI) patients, using voxel-mirrored homotopic connectivity (VMHC), and their relationships with clinical features. Totally, 16 male and 2 female acute OGI patients and 18 sex, age, and education-matched healthy volunteers were enrolled in the study. All subjects were scanned through functional magnetic resonance imaging (fMRI). Receiver operating characteristic (ROC) curves analyses had been used to identify the VMHC in these brain areas could be used as biomarkers to distinguish OGI and from healthy control (HC). The mean VMHC values in multiple brain areas and clinical OGI manifestations were evaluated with a Pearson correlation analysis. OGI patients had significantly decreased VMHC in the bilateral calcarine/lingual/cuneus (BA18, 19, 30) and middle occipital gyrus (BA18, 19). The OGI patients had abnormal interhemispheric FC in the dorsal visual pathway, which may represent the pathophysiological mechanism that underlies acute vision loss after OGI

Encapsulation of caffeine into starch matrices: Bitterness evaluation and suppression mechanism

In this study, caffeine (CA) was encapsulated into food-grade starch matrices, including swelled starch (SS), porous starch (PS), and V-type starch (VS). The bitterness of the microcapsules and suppression mechanisms were investigated using an electronic tongue, molecular dynamics (MD) simulation and the in vitro release kinetics of CA. All the CA-loaded microcapsules showed a lower bitterness intensity than the control. The MD results proved that the weak interactions between starch and CA resulted in a moderate CA release rate for SS-CA microcapsules. The PS-CA microcapsule presented the longest CA release, up to 40 min, whereas the VS-CA microcapsule completely released CA in 9 min. The CA release rate was found to be related to the microcapsule structure and rehydration properties. A low CA bitterness intensity could be attributed to a delay in the CA release rate and resistance to erosion of the microcapsules. The results of this work are valuable for improving starch-based microcapsules (oral-targeted drug-delivery systems) by suppressing the bitterness of alkaloid compounds

Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism.

Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis

Plastome phylogenomics and morphological traits analyses provide new insights into the phylogenetic position, species delimitation and speciation of Triplostegia (Caprifoliaceae)

Background The genus Triplostegia contains two recognized species, T. glandulifera and T. grandifora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. Results Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandifora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentifed as T. glandulifera, but difers in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96Ma, and within it T. glandulifera diverged 7.94Ma. Triplostegia grandifora and sp. A diverged 1.05Ma, perhaps in response to Quaternary climate fuctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. Conclusions Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identifed that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegi