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Background and Aims: Apolipoprotein A‐1 (ApoA‐1), the major apolipoprotein of high‐density lipoprotein, plays anti‐atherogenic role in cardiovascular diseases and exerts anti‐inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA‐1 in hepatic ischaemia–reperfusion (I/R) injury is unknown. Methods: In this study, we measured ApoA‐1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA‐1 knockout mice, ApoA‐1 mimetic peptide D‐4F treatment mice and corresponding control mice to examine the effect of ApoA‐1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study. Results: The results showed that ApoA‐1 expression was down‐regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA‐1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA‐1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA‐1 deficiency. Furthermore, the up‐regulated pyroptosis process was testified to be mediated by ApoA‐1 through TLR4–NF‐κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D‐4F ameliorated hepatic I/R injury. Conclusions: Our study has identified the protective role of ApoA‐1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4–NF‐κB pathway. The effect of ApoA‐1 may provide a novel therapeutic approach for hepatic I/R injury. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the "Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)" based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Portal vein system thrombosis (PVST) is a frequent and potentially life-threatening complication after laparoscopic splenectomy (LS) in cirrhotic patients with hypersplenism. The mechanisms and risk factors of PVST are poorly understood. This study investigated risk factors for PVST following LS in cirrhotic patients with hypersplenism.Materials and Methods: A total of 56 consecutive cirrhotic patients with hypersplenism who underwent successful LS between 2013 and 2014 were included in this retrospective study. Based on the absence or presence of postoperative PVST on postoperative day (POD) 7, the patients were divided into non-PVST and PVST groups. Demographic and preoperative factors were analyzed.Results: PVST increased in size in 24 (42.9%) of 56 patients after LS on POD 7. Logistic multivariate regression showed that a portal vein diameter >13 mm (relative risk 35.796, 95% confidence interval 4.534-282.614, and P = .001) and age >50 years (relative risk 20.127, 95% confidence interval 3.598-112.578, and P = .001) were significant independent risk factors for PVST. The incidence of PVST after LS in the portal vein diameter >13 mm group was significantly higher than that in the portal vein diameter ≤13 mm group (P = .001). Similarly, the incidence of PVST after LS in the age >50 years group was significantly higher than that in the age ≤50 years group (P = .001).Conclusion: A portal vein diameter >13 mm and age >50 years are independent risk factors for PVST after LS in cirrhotic patients with hypersplenism due to portal hypertension. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to isolate, identify, and analyze diabetes-related protein changes that occur in neural retinas in vivo. Methods: Total proteins were extracted from neural retinas of normal and 8-weeks diabetic Sprague-Dawley (SD) rats and separated by two-dimensional gel electrophoresis (2-DE). Some protein spots exhibiting statistically significant variations (p < 0.05) were selected randomly and identified by mass spectrometry (MS or MS/MS). The protein α A-crystallin was chosen as a target for specific immunodetection using Western blot to corroborate the variation found by 2-DE. Results: Twenty protein spots identified included α A-crystallin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamine (Gln) synthetase, and so forth. Western blotting analyses confirmed that α A-crystallin protein expression was upregulated in diabetic retina. Conclusions: In this study, we isolate, identify, and analyze diabetes-related protein changes that occur in neural retinas in vivo. Further investigation of candidate proteins may identify novel pharmacological targets for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: Adoptive transfusion of splenocytes from long-term survivors of a tolerance model of rat orthotopic liver transplantation can induce acceptance of liver allografts in a rejection model preconditioned with donor γ-irradiation before liver transplantation. Recent studies suggest that the regulatory T cells (Treg cells) in splenocytes from long-term survivors play an important role in the induction of liver graft tolerance, but this observation was made from a rejection model preconditioned with donor γ-irradiation; little is known about the role of Treg cells in liver graft rejection using a naive rejection model. In this study, we examined the therapeutic potential of CD4+CD25+ Treg cells in a naive rejection model of rat liver transplantation. Methods: Freshly isolated or ex vivo alloantigen-stimulated CD4+CD25+ Treg cells (1 × 106 cells) from naive Lewis RT1 (LEW) rats were adoptively transferred into another LEW rat on days 1 and 7 after liver transplantation from a Dark Agouti RT1a (DA) rat. Recipients were treated with or without oral tacrolimus (FK506) (0.1 mg/kg/day) from days 1 to 7 after transplantation. For ex vivo alloantigen-stimulation, CD4+CD25+ Treg cells from LEW rats were cocultured with mitomycin C–treated DA (donor alloantigen specific) or Brown Norway (BN)(RT1n, third party) splenocytes for 72 hours. Ex vivo alloantigen-specific CD4+CD25− T-cell proliferation responses were assessed with fresh and stimulated CD4+CD25+ Treg cells. Results: Freshly isolated, donor alloantigen-stimulated and third-party alloantigen- stimulated CD4+CD25+ Treg cells suppressed antigen-specific CD4+CD25− T-cell proliferation ex vivo, and adoptive transfusion of these 3 kinds of CD4+CD25+ Treg cells prolonged survival of the liver allografts. The group transfused with the donor alloantigen-stimulated CD4+CD25+ Treg cells had the greatest mean survival among the 3 groups (fresh Treg cells, 21 ± 2 days, n = 6; third-party alloantigen-stimulated Treg cells, 20 ± 2 days, n = 6; donor alloantigen-stimulated Treg cells, 30 ± 2 days, n = 6). When combined with short-term tacrolimus administration, adoptive transfusion of donor antigen-stimulated Treg cells induced the greatest survival time in recipients (greater than 60 days; n = 6). Conclusion: Adoptive transfusion of ex vivo donor alloantigen-stimulated CD4+CD25+ Treg cells combined with short-term tacrolimus treatment may represent a new strategy for preventing rejection after liver transplantation. [Copyright &y& Elsevier]

Highlights: [•] Caleosins in Arabidopsis are divided into two types, L-caleosin and H-caleosin. [•] L-caleosin may evolve from H-caleosin. [•] Segmental and tandem duplication are main reasons for caleosin family expansion. [•] The expression patterns of caleosins were investigated in silico. [•] Caleosin may be involved in signal transduction and lipid accumulation. [Copyright &y& Elsevier]

Background: To investigate hepatic regenerative response and associated mechanisms in different-size liver grafts in the rat. Methods: Rat models of different-size-graft liver transplantation (whole, 50%-size, or 30%-size) were established, with a sham operation group serving as a control. Portal pressure, graft injury, interleukin 6 (IL-6), signal transducer and activator of transcription (Stat3), mitogen-activated protein kinase (MAPK), cyclin D1, and proliferating cell nuclear antigen (PCNA) were all assessed. Results: The portal pressure was significantly higher and hepatic injury more severe in the smaller sized groups than in the whole graft group, especially in the 30%-size grafts. Hepatic IL-6 and tumor necrosis factor-α (TNF-α) levels in the two smaller sized groups were significantly higher than in the whole graft group, while IL-6 levels appeared to be negatively associated with graft sizes. Downstream markers of IL-6, Stat3 and MAPK phosphorylation, cyclin D1, and PCNA expression were also markedly increased in the small-sized grafts compared with the whole grafts, and appeared to positively correlate with early measurements of portal pressure and subsequent hepatic injury. Conclusion: Vigorous hepatic regeneration in small-for-size liver grafts may be associated with highly activated IL-6/Stat3 and MAPK signaling, which may in turn correlate with graft size, portal pressure, and hepatic injury. [Copyright &y& Elsevier]