Ischemia reperfusion injury of the marginal liver: identification and evaluation of novel therapeutic strategies

The need for liver grafts has constantly increased in the past decades. The discrepancy between the declining availability of donor organs and the exponentially growing demand has becoming more and more obvious. To expand the donor organ pool by accepting marginal organs such as steatotic livers and aged livers is one of the strategies to solve this problem. However it is well accepted that marginal livers are more vulnerable to ischemia reperfusion injury (IRI), which is considered as one of the major risks of post-operative morbidity and mortality. Recent studies suggested that there were common mechanisms involved in both steatosis respectively senescence and the IRI processes. We hypothesized that therapeutic strategies targeting these common mechanisms might be especially useful in protecting marginal livers from IRI. We put our emphasis on exploring the common mechanisms in senescence/steatosis process and IRI process. We also aimed to identify and to evaluate one of these therapeutic strategies targeting the common mechanisms to protect steatotic livers from IRI. Furthermore, we discuss common mechanisms and suggest novel therapeutic strategies targeting common mechanisms in all three, steatosis, senescence and IRI processes. ..

Identification of Proteins Interacting with Cytoplasmic High-Mobility Group Box 1 during the Hepatocellular Response to Ischemia Reperfusion Injury

Ischemia/reperfusion injury (IRI) occurs inevitably in liver transplantations and frequently during major resections, and can lead to liver dysfunction as well as systemic disorders. High-mobility group box 1 (HMGB1) plays a pathogenic role in hepatic IRI. In the normal liver, HMGB1 is located in the nucleus of hepatocytes; after ischemia reperfusion, it translocates to the cytoplasm and it is further released to the extracellular space. Unlike the well-explored functions of nuclear and extracellular HMGB1, the role of cytoplasmic HMGB1 in hepatic IRI remains elusive. We hypothesized that cytoplasmic HMGB1 interacts with binding proteins involved in the hepatocellular response to IRI. In this study, binding proteins of cytoplasmic HMGB1 during hepatic IRI were identified. Liver tissues from rats with warm ischemia reperfusion (WI/R) injury and from normal rats were subjected to cytoplasmic protein extraction. Co-immunoprecipitation using these protein extracts was performed to enrich HMGB1-protein complexes. To separate and identify the immunoprecipitated proteins in eluates, 2-dimensional electrophoresis and subsequent mass spectrometry detection were performed. Two of the identified proteins were verified using Western blotting: betaine–homocysteine S-methyltransferase 1 (BHMT) and cystathionine γ-lyase (CTH). Therefore, our results revealed the binding of HMGB1 to BHMT and CTH in cytoplasm during hepatic WI/R. This finding may help to better understand the cellular response to IRI in the liver and to identify novel molecular targets for reducing ischemic injury

New NIR spectroscopy based method to determine ischemia in vivo in liver – a first study on rats

In this study we analysed ischemic rat liver lobes with Near Infrared Spectroscopy (NIRS) to evaluate the potential of NIRS as predictor of ischemic reperfusion injury (IRI). We were able to predict duration of ischemia using visible and near infrared light

Probiotic Lactobacillus sp. Strains Inhibit Growth, Adhesion, Biofilm Formation, and Gene Expression of Bacterial Vaginosis-Inducing Gardnerella vaginalis

Gardnerella vaginalis contributes significantly to bacterial vaginosis, which causes an ecological imbalance in vaginal microbiota and presents with the depletion of Lactobacillus sp. Lactobacillus supplementation was reported to be an approach to treat bacterial vaginosis. We investigated the applicability of three Lactobacillus sp. strains (Lactobacillus delbrueckii DM8909, Lactiplantibacillus plantarum ATCC14917, and Lactiplantibacillus plantarum ZX27) based on their probiotic abilities in vitro. The three candidate Lactobacillus sp. strains for bacterial vaginosis therapy showed distinct properties in auto-aggregation ability, hydrophobicity, adhesion to cervical epithelial cells, and survivability in 0.01% hydrogen peroxide. Lpb. plantarum ZX27 showed a higher yield in producing short-chain fatty acids and lactic acid among the three candidate strains, and all three Lactobacillus sp. strains inhibited the growth and adhesion of G. vaginalis. Furthermore, we discovered that the culture supernatant of Lactobacillus sp. exhibited anti-biofilm activity against G. vaginalis. In particular, the Lpb. plantarum ZX27 supernatant treatment decreased the expression of genes related to virulence factors, adhesion, biofilm formation, metabolism, and antimicrobial resistance in biofilm-forming cells and suspended cells. Moreover, Lactobacillus sp. decreased the upregulated expression of interleukin−8 in HeLa cells induced by G. vaginalis or hydrogen peroxide. These results demonstrate the efficacy of Lactobacillus sp. application for treating bacterial vaginosis by limiting the growth, adhesion, biofilm formation, and virulence properties of G. vaginalis

Halogenated Ti3C2 MXenes with Electrochemically Active Terminals for High-Performance Zinc Ion Batteries

The class of two-dimensional metal carbides and nitrides known as MXenes offer a distinct manner of property tailoring for a wide range of applications. The ability to tune the surface chemistry for expanding the property space of MXenes is thus an important topic, although experimental exploration of surface terminals remains a challenge. Here, we synthesized Ti3C2 MXene with unitary, binary, and ternary halogen terminals, e.g., -Cl, -Br, -I, -BrI, and -ClBrI, to investigate the effect of surface chemistry on the properties of MXenes. The electrochemical activity of Br and I elements results in the extraordinary electrochemical performance of the MXenes as cathodes for aqueous zinc ion batteries. The -Br- and -I-containing MXenes, e.g., Ti3C2Br2 and Ti3C2I2, exhibit distinct discharge platforms with considerable capacities of 97.6 and 135 mA.g(-1). Ti3C2 (BrI) and Ti3C2 (ClBrI) exhibit dual discharge platforms with capacities of 117.2 and 106.7 mAh.g(-1). In contrast, the previously discovered MXenes Ti3C2Cl2 and Ti3C2 (OF) exhibit no discharge platforms and only similar to 50% of capacities and energy densities of Ti3C2Br2. These results emphasize the effectiveness of the Lewis-acidic-melt etching route for tuning the surface chemistry of MXenes and also show promise for expanding the MXene family toward various applications.Funding Agencies|National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [51902320, 21805295, U2004212]; International Partnership Program of Chinese Academy of Sciences [174433KYSB20190019]; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang [2019R01003]; Ningbo Top-Talent Team Program; GRF [N_CityU11305218]; Science Technology and Innovation Committee of Shenzhen Municipality [JCYJ20170818103435068]; Knut and Alice Wallenberg FoundationKnut &amp; Alice Wallenberg Foundation [KAW 2015.0043]; Swedish Foundation for Strategic Research (SSF)Swedish Foundation for Strategic Research [EM16-0004, RIF 14-0074]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]</p