Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium

Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by impairing autophagosome–lysosome fusion. We hypothesized that autophagy flux altered by CQ has a considerable influence on the lipid composition of endothelial cells. Thus, we investigated endothelial responses induced by CQ on human microvascular endothelial cells (HMEC-1). HMEC-1 cells after CQ exposure were measured using a combined methodology based on label-free Raman and fluorescence imaging. Raman spectroscopy was applied to characterize subtle chemical changes in lipid contents and their distribution in the cells, while the fluorescence staining (LipidTox, LysoTracker and LC3) was used as a reference method. The results showed that CQ was not toxic to endothelial cells and did not result in the endothelial inflammation at concentrations of 1–30 µM. Notwithstanding, it yielded an increased intensity of LipidTox, LysoTracker, and LC3 staining, suggesting changes in the content of neutral lipids, lysosomotropism, and autophagy inhibition, respectively. The CQ-induced endothelial response was associated with lipid accumulation and was characterized by Raman spectroscopy. CQ-induced autophagosome accumulation in the endothelium is featured by a pronounced alteration in the lipid profile, but not in the endothelial inflammation. Raman-based assessment of CQ-induced biochemical changes offers a better understanding of the autophagy mechanism in the endothelial cells.     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

宰前倒挂应激对鸭血凝胶特性的影响

宰前倒挂因能有效提高屠宰效率成为肉鸭宰杀前必经的一个工艺过程，但倒挂往往会加剧肉鸭的应激程度，影响其血液品质，已成为工厂生产中亟待解决的问题。因此，本实验旨在借助血液学与凝血相关指标探究宰前倒挂应激对鸭血凝胶特性的影响。在屠宰前，将40 只樱桃谷鸭随机分为2 个处理组：对照组和宰前倒挂组（宰前倒挂2.5 min），屠宰后采集血样并制备血凝块，随后分析血液指标（应激指标、血液学指标、凝血指标）以及鸭血凝胶特性。结果表明，宰前倒挂组鸭血中皮质酮激素及促肾上腺皮质激素的水平均高于对照组，说明实验所建立宰前倒挂模型成立。倒挂应激后，红细胞计数、血小板计数、血红蛋白质量浓度增加，红细胞比容、平均红细胞体积及平均血小板体积增大；凝血酶原的水平极显著上升（P＜0.01），组织因子的水平显著上升（P＜0.05）。宰前倒挂最终导致鸭血凝胶化加快，鸭血凝胶体系中水分迁移速率增大，结合水与自由水比例减少，不易流动水比例增大，质构特性和保水性变差。研究揭示了宰前倒挂应激通过影响鸭血的血液学指标和凝血系统从而改变其凝胶行为及凝胶特性，可为工厂改善应激对鸭血凝胶品质的影响提供理论依据。