Clinicopathologic significance of LAIR-1 expression in hepatocellular carcinoma

Aim

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune inhibitory receptor which is expressed within most types of hematopoietic cells and negatively regulates immune responses. Recently, we found LAIR-1 expression to be present within tumors of nonhematopoietic lineages. However, the roles of LAIR-1 in hepatocellular carcinoma (HCC) have yet to be examined. The purpose of this study was to investigate the expression of LAIR-1 in HCC tissue and assess its clinical significance at this site.

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/Hypothesis

Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study.

Caveolin-1 in skin aging – From innocent bystander to major contributor

Caveolin-1 (Cav-1) appears to be both a pathophysiological contributor and a target in different inflammatory and hyperproliferative skin conditions as well as in skin aging. Skin fibroblasts demonstrate an up-regulation of Cav-1 expression both in chronological and UV-induced aging, and such an up-regulation was observed both in vitro and in vivo. Typical alterations in aging skin involve a reduction of the dermis thickness, a significant expansion of the dermal white adipose tissue as well as modifications of the content and distribution of hyaluronan, impairment of autophagic flux, a reduction of collagen expression and an increase in tissue inflammation. All of these phenomena can be connected with changes in Cav-1 expression in the aging skin. Modified expression of Cav-1 can also significantly influence the mechanical properties of individual skin layers, thus changing the total mechanical stability of the layered composite skin/WAT, leading to typical structural modifications of the skin surface in the aging skin. Selective reduction of Cav-1 expression has the potential to exert anti-aging effects on the skin.     

Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

整合素α5β1在苯妥英钠促进大鼠PDLSCs和BMMSCs黏附于牙骨质中的作用

目的 探讨在苯妥英钠(Phenytoin,PHT)促进大鼠牙周膜干细胞(Rat periodontal ligament stem cells,rPDLSCs)、大鼠骨髓间充质干细胞(Rat Bone Marrow Mesenchymal Stem Cells,rBMMSCs)黏附于牙骨质过程中,整合素α5β1(Integrin α5β1)起到的作用。方法 提取大鼠BMMSCs和PDLSCs,培养并纯化。通过细胞鉴定后,将获得的两种细胞各分为4组:40 mg/L PHT处理组、40 mg/L PHT+整合素α5抗体处理组、40 mg/L PHT+整合素β1抗体处理组、PBS处理组,每组细胞放入置有牙骨质片的96孔板处理4 h后,检测黏附于牙骨质片上的细胞量并做以比较。最后,利用qRT-PCR和Western blot检测40 mg/L PHT组与对照组细胞的整合素α5、β1亚基的mRNA与蛋白表达量。结果 40 mg/L PHT可促进rBMMSCs及rPDLSCs黏附于牙骨质片,加入整合素α5、β1抗体后,均明显抑制了40 mg/L PHT对rBMMSCs、rPDLSCs黏附于牙骨质的促进作用(P＜0.01)。qRT-PCR、Western-blot结果显示PHT处理组的整合素α5、β1亚基表达量高于空白对照组(P＜0.05)。结论 40 mg/L PHT能促进rBMMSCs、rPDLSCs黏附于牙骨质,该作用与整合素α5β1的表达上调密切相关。     

HBV-ACLF患者血清miR-122和 HMGB1水平及其与病情、预后的关系

[摘要]　目的　探究HBV相关慢加急性肝衰竭（HBV-related acute-on-chronic liver failure, HBV-ACLF）患者血清中微小核糖核酸（microRNA, miR）-122和高迁移率族蛋白1（high-mobility group box-B1, HMGB1）水平及其与病情、预后的关系。方法　回顾性分析2016年1月—2018年1月我院收治的120例HBV-ACLF患者的一般及临床资料。根据临床结局，将患者分为存活组（53例）和死亡组（67例）。比较2组患者的一般资料、实验室检查指标及血清miR-122、HMGB1水平。多因素Logistic回归分析影响患者预后的因素。Pearson检验分析miR-122、HMGB1水平分别与TBIL、PA、终末期肝病评分模型（the model of end-stage liver disease score, MELD）评分的相关性。ROC曲线分析miR-122和HMGB1水平对患者的死亡预测价值，获得最佳临界值。根据临界值将患者分为A组、B组和C组，用Kaplan-Meier法绘制生存曲线，比较3组患者在3年随访期间的生存率。结果　存活组和死亡组患者的年龄、身体质量指数、并发症、病情分期、MELD评分、ALB、球蛋白、TBIL、ALT、AST、LDH、PT、PTA、HBV DNA、miR-122、HMGB1相比，差异均具有统计学意义（P均＜0.05）。年龄、并发症、病情分期、MELD评分、TBIL、PT、PTA、miR-122、HMGB1均是影响患者预后的危险因素（P均＜0.05）。miR-122、HMGB1水平分别与TBIL、MELD评分呈显著正相关，与PTA呈显著负相关（P均＜0.05）。miR-122和HMGB1预测患者死亡的最佳临界值分别为31.42和14.56 μg/L。A组患者预后3年内生存率显著高于B组和C组（P均＜0.05）。结论　miR-122和HMGB1水平与HBV-ACLF患者的病情和死亡预后密切相关，可间接反映患者的病情严重程度，在HBV-ACLF的诊断及预后中具有重要价值。