Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated. In this study, we aim to investigate the effect and potential mechanism of MSCs against liver I/R injury. Effects of MSCs were studied in mice liver I/R injury model and in a hypoxia/reoxygenation (H/R) model of L02 hepatocytes. The potential mechanisms of MSCs on these in vivo and in vitro I/R-induced hepatocellular apoptosis models were studies. Accompanied by the improvement of hepatic damage, MSCs exhibited capabilities of controlling mitochondrial quality, shown by reduced mitochondrial reactive oxygen species (mtROS) overproduction, decreased the accumulation of mitochondrial fragmentation, restored ATP generation and upregulated mitophagy. Furthermore, we descripted a potential mechanism of MSCs on upregulating mitophagy and found that the reduced Parkin and PINK1 expression and inactivated AMPKα pathway were observed in the liver tissue in I/R model. These effects were reversed by MSCs treatment. In vitro study showed that MSCconditioned medium (MSC-CM) suppressed hepatocellular apoptosis and inhibited mtROS accumulation in the H/R environment. And these effects of MSC-CM were partially blocked after the cells were transfected with PINK1 siRNA or added with dorsomorphin. Collectively, our findings provide a novel pharmacological mechanism that MSCs exert hepatoprotective effect in liver I/R injury via upregulating PINK1-dependent mitophagy. In addition, this effect might be attributed to the modulation of AMPKα activation.

As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC‐derived extracellular vesicles (MSC‐EVs) are newly uncovered messengers for intercellular communication. Herein, it is reported that umbilical cord‐derived MSCs (UC‐MSCs) improve liver IRI in mice through their secreted EVs. It is also visualized that UC‐MSC‐EVs mainly concentrate in liver after 6 h of reperfusion. Furthermore, UC‐MSC‐EVs are found to significantly modulate the membranous expression of CD154 of intrahepatic CD4+ T cells, which is an initiation of inflammatory response in liver and can aggravate liver IRI. Mechanistically, protein mass spectrum analysis is performed and it is revealed that Chaperonin containing TCP1 subunit 2 (CCT2) enriches in UC‐MSC‐EVs, which regulates the calcium channels to affect Ca2+ influx and suppress CD154 synthesis in CD4+ T cells. In conclusion, these results highlight the therapeutic potential of UC‐MSC‐EVs in attenuating liver IRI. This finding suggests that CCT2 from UC‐MSC‐EVs can modulate CD154 expression of intrahepatic CD4+ T cells during liver IRI through the Ca2+‐calcineurin‐NFAT1 signaling pathway.

There is a demand to develop molecular catalysts promoting the hydrogen evolution reaction (HER) with a high catalytic rate and a high tolerance to various inhibitors, such as CO and O2. Herein we report a cobalt catalyst with a penta‐dentate macrocyclic ligand (1‐Co), which exhibits a fast catalytic rate (TOF=2210 s−1) in aqueous pH 7.0 phosphate buffer solution, in which proton transfer from a dihydrogen phosphate anion (H2PO4−) plays a key role in catalytic enhancement. The electrocatalyst exhibits a high tolerance to inhibitors, displaying over 90 % retention of its activity under either CO or air atmosphere. Its high tolerance to CO is concluded to arise from the kinetically labile character of undesirable CO‐bound species due to the geometrical frustration posed by the ligand, which prevents an ideal trigonal bipyramid being established.

Objectives: Transfusion of umbilical cord-derived mesenchymal stem cells (UC-MSCs)is a novel strategy for treatment of various liver diseases. However, the therapeutic effect of UC-MSCs is limited because only a few UC-MSCs migrate towards the damaged regions. In this study, we observed the effects of autophagy on the migration of UC-MSCs in vitro and in a model of liver ischaemia/reperfusion (I/R) injury. Materials and Methods:We investigated the effects of autophagy on the status of the cell, release of anti-inflammatory factors and migration of UC-MSCs in vitro. The therapeutic effects and in vivo migration of rapamycin-preconditioned UC-MSCs were observed in a C57/B6 mouse model of liver I/R injury.Results: Induction of autophagy by rapamycin enhanced the ability of UC-MSCs to migrate and release anti-inflammatory cytokines as well as increased expression of CXCR4 without affecting cell viability. Inhibition of CXCR4 activation markedly decreased migration of these cells. In a mouse model of liver I/R injury, we found significantly upregulated expression of CXCR12 in the damaged liver. More rapamycin-preconditioned UC-MSCs migrated towards the ischaemic regions than 3-methyladenine-preconditioned or non-preconditioned UC-MSCs, leading to improvement in hepatic performance, pathological changes and levels of inflammatory cytokines. These effects were abolished by AMD3100.