Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal Cancer

Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.

PCSK9 and triglyceride-rich lipoprotein metabolism

Pro-protein convertase subtilisin-kexin 9 （PCSK9） is known to affect low-density lipoprotein （LDL） metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipopro- teins, especially triglyceride-rich lipoproteins （TRL）. This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of （1） a correlation between plasma PCSK9 and triglyceride （TG） levels in health and disease, （2） a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, （3） an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, （4） an effect of PCSK9 on postprandial lipemia, （5） an effect of PCSK9 on adipose tissue biology, （6） an effect of PCSK9 on apolipoprotein B production from the liver and intestines, （7） an effect of PCSK9 on receptors other than low density lipoprotein receptor （LDLR） that are involved in TRL metabolism, and （8） an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge.

Antiviral activity of quercetin-3-β-O-D-glucoside against Zika virus infection

Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infections are associated with fetal microcephaly, as well as neurological complications in humans. The virus can be shed in the semen and vaginal secretions of humans, leading to sexual transmission, and unexpectedly ZIKV infections cause severe damage to the male reproductive organs in male mice （Govero et al., 2016; Ma et al., 2016）.

Remodeling of the plasma for sperm-egg recognition： proteins membrane in preparation roles of acrosomal

The interaction of sperm with the egg＇s extracellular matrix, the zona pellucida （ZP） is the first step of the union between male and female gametes. The molecular mechanisms of this process have been studied for the past six decades with the results obtained being both interesting and confusing. In this article, we describe our recent work, which attempts to address two lines of questions from previous studies. First, because there are numerous ZP binding proteins reported byvarious researchers, how do these proteins act together in sperm-ZP interaction？ Second, why do a number of acrosomal proteins have ZP affinity？ Are they involved mainly in the initial sperm-ZP binding or rather in anchoring acrosome reacting/reacted spermatozoa to the ZP？ Our studies reveal that a number of ZP binding proteins and chaperones, extracted from the anterior sperm head plasma membrane, coexist as high molecular weight （HMW） complexes, and that these complexes in capacitated spermatozoa have preferential ability to bind to the ZP. Zonadhesin （ZAN）, known as an acrosomal protein with ZP affinity, is one of these proteins in the HMW complexes. Immunoprecipitation indicates that ZAN interacts with other acrosomal proteins, proacrosin/acrosin and sp32 （ACRBP）, also present in the HMW complexes. Immunodetection of ZAN and proacrosin/acrosin on spermatozoa further indicates that both proteins traffic to the sperm head surface during capacitation where the sperm acrosomal matrix is still intact, and therefore they are likely involved in the initial sperm-ZP binding step.