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Salt sensitivity concerns blood pressure alterations after a change in salt intake (sodium chloride). The heart is a pump, and vessels are tubes; sodium can affect both. A high salt intake increases cardiac output, promotes vascular dysfunction and capillary rarefaction, and chronically leads to increased systemic vascular resistance. More recent findings suggest that sodium also acts as an important second messenger regulating energy metabolism and cellular functions. Besides endothelial cells and fibroblasts, sodium also affects innate and adaptive immunometabolism, immune cell function, and influences certain microbes and microbiota-derived metabolites. We propose the idea that the definition of salt sensitivity should be expanded beyond high blood pressure to cellular and molecular salt sensitivity. [ABSTRACT FROM AUTHOR]

Aim: Six‐month recipient mortality after adult‐to‐adult living‐donor liver transplantation (LDLT) remains high. Early and accurate prediction of recipient outcome and continuous monitoring of recipient severity after surgery are both essential for guiding appropriate care. This study was designed to identify early post‐transplant parameters associated with 6‐month mortality, and thereby to construct a discriminatory prognostic index (PI). Methods: We retrospectively analyzed 400 consecutive primary adult‐to‐adult LDLTs in our center (2006–2017). Perioperative variables were comprehensively analyzed for their accuracy in predicting recipient mortality by comparing the area under the receiver operating characteristic (AUROC) of each factor. Results: The AUROCs of preoperative predictive factors, for example, Model for End‐stage Liver Disease (MELD) score and donor age, were 0.56 and 0.64, respectively, whereas those of post‐transplant platelet count (PLT), total bilirubin (T‐BIL), and prothrombin time – international normalized ratio (INR) on postoperative day (POD)‐7−14 were 0.71/0.84, 0.68/0.82, and 0.71/0.78, respectively. Logistic regression analysis provided a formula: PIPOD‐14 = 3.39 + 0.12 × PLTPOD‐14 − 0.09 × T‐BILPOD‐14 − 1.23 × INRPOD‐14, indicating a high AUROC of 0.87. Recipient 6‐month survival with PIPOD‐14 < 2.38 (n = 173) was 71.7%, whereas that with PIPOD‐14 ≥ 2.38 (n = 222) was 97.7% (P < 0.001). The AUROCs of PIPOD‐7 were as high as 0.8 in the subgroups with younger donors (<50 years of age), right lobe grafts, ABO‐identical/compatible combinations, or low MELD score (<20), indicating usefulness of PI to identify unexpectedly complicated cases within the first week. Conclusions: A novel, post‐transplant survival estimator, PI, accurately predicts recipient 6‐month mortality within 1–2 weeks after adult LDLT. Daily monitoring of PI could facilitate early interventions including retransplantation in critically ill patients. [ABSTRACT FROM AUTHOR]

Hepatic ischemia/reperfusion injury (IRI) often causes serious complications in liver surgeries, including transplantation. Complement activation seems to be involved in hepatic IRI; however, no complement-targeted intervention has been clinically applied. We investigated the therapeutic potential of Properdin-targeted complement regulation in hepatic IRI. Male wild-type mice (B10D2/nSn) were exposed to 90-minute partial hepatic IRI to the left and median lobes with either monoclonal anti-Properdin-antibody (Ab) or control-immunoglobulin (IgG) administration. Since the complement system is closely involved in liver regeneration, the influence of anti-Properdin-Ab on liver regeneration was also evaluated in a mouse model of 70% partial hepatectomy. Anti-Properdin-Ab significantly reduced serum transaminases and histopathological damages at 2 and 6 hours after reperfusion ( P < 0.001, respectively). These improvements at 2 hours was accompanied by significant reductions in CD41+ platelet aggregation ( P =0.010) and ssDNA+ cells ( P < 0.001), indicating significant amelioration in hepatic microcirculation and apoptosis, respectively. Characteristically, F4/80+ cells representing macrophages, mainly Kupffer cells, were maintained by anti-Properdin-Ab ( P < 0.001). Western blot showed decreased phosphorylation of only Erk1/2 among MAPKs ( P =0.004). After 6 hours of reperfusion, anti-Properdin-Ab significantly attenuated the release of HMGB-1, which provokes the release of proinflammatory cytokines/chemokines ( P =0.002). Infiltration of CD11b+ and Ly6-G+ cells, representing infiltrating macrophages and neutrophils, respectively, were significantly alleviated by anti-Properdin-Ab (both P < 0.001). Notably, anti-Properdin-Ab did not affect remnant liver weight and BrdU+ cells at 48 hours after 70% partial hepatectomy ( P =0.13 and 0.31, respectively). In conclusion, Properdin inhibition significantly ameliorates hepatic IRI without interfering with liver regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that company Alexion Pharmaceuticals, Inc. provided anti-Properdin antibody., (Copyright © 2023 Kusakabe, Hata, Tajima, Miyauchi, Zhao, Kageyama, Tsuruyama and Hatano.)

Meiosis is a key mechanism that ensures sexual reproduction and creates genetic diversity. Here we describe a method that induces fetal oocytes and the prophase of the first meiotic division from mouse pluripotent stem cells (PSCs) under defined conditions. PSCs are induced into epiblast-like cells (EpiLCs), which are in turn induced into primordial germ cell-like cells (PGCLCs). PGCLCs are expanded robustly in the presence of forskolin and rolipram, which elevate intracellular cyclic AMP levels. The expanded PGCLCs comprehensively erase their DNA methylome in a manner that recapitulates genome-wide DNA demethylation in germ cells in vivo, and are in turn induced efficiently into the oogenic pathway and the prophase of the first meiotic division up to the pachytene stage in response to bone morphogenetic protein and retinoic acid. This in vitro strategy provides a powerful foundation for exploring the mechanisms of initiation and progression of mammalian oogenesis and meiosis., (© 2018 Elsevier Inc. All rights reserved.)