Cerebrospinal fluid proteomics, a branch of proteomics, is aimed to separate different types of cerebrospinal fluid proteins and identify differentially expressed protein sites through core analysis techniques.Since cerebrospinal fluid is directly connected with extracellular fluid of brain tissue, the abnormal change in the central nervous system could influence the composition of cerebrospinal fluid, such as peptides and proteins.Cerebrospinal fluid proteomics research gives insight into understanding of physiological and pathological changes of central nervous system(CNS), which is a supplement of cytological examination and biochemical test for CNS, and the technology provides a support for diagnosis and treatment of CNS diseases.Detecting cerebrospinal fluid proteomics is of great importance for the diagnosis,treatment and prognosis of CNS diseases.

C-reactive protein (CRP), an acute-phase protein with an ability to bind to nuclear antigen, has been reported to regulate cytokine secretion and modulate immune responses. We previously reported that activated syngeneic lymphocyte-derived apoptotic DNA (apopDNA) could induce macrophage activation and contribute to the initiation and progression of lupus nephritis. It is reasonable to hypothesize that CRP might regulate apopDNA-induced macrophage activation. Herein, CRP was shown to promote macrophage-mediated apopDNA uptake by binding to apopDNA (CRP/apopDNA complex). Notably, CRP/apopDNA treatment inhibited the production of inflammatory cytokines and chemokines by macrophages which could be induced by apopDNA alone. Further coculture and transwell studies revealed that CRP/apopDNA-induced macrophages prohibited apopDNA-induced macrophage activation in an IL-10 dependent manner. These results provide insight into the potential mechanism of CRP regulatory activity in macrophage activation induced by apopDNA in the context of lupus nephritis and other autoimmune diseases.
Animals ; C-Reactive Protein ; metabolism ; pharmacology ; Cell Line, Tumor ; DNA ; metabolism ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Female ; Lupus Erythematosus, Systemic ; metabolism ; Lupus Nephritis ; metabolism ; Macrophage Activation ; drug effects ; physiology ; Mice ; Mice, Inbred BALB C ; Protein Binding ; Real-Time Polymerase Chain Reaction

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.