Shuhong Luo

Background: Autoantibodies against tumor-associated antigens (TAAs) are promising noninvasive cancer biomarkers due to their specificity and stability. Gastric cancer (GC) diagnosis often requires invasive procedures, emphasizing the need for reliable blood-based biomarkers. Objective: This study assessed whether serum IgG and IgA autoantibodies, individually or combined, could serve as noninvasive biomarkers for gastric cancer. Experimental design: We analyzed 27 autoantibodies in serum from 265 healthy controls, 296 GC patients, and 195 gastritis patients using protein microarray. Autoantibody levels and the IgG/IgA ratio were calculated. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. Results: We identified 24 differentially expressed autoantibodies (DEAs) for IgA and 17 for IgG between GC patients and controls. In distinguishing GC from gastritis, 20 DEAs for IgA and 23 for IgG were significant. The IgG/IgA ratio of MIP1 beta had the highest diagnostic performance between atrophic gastritis and GC, while MMP7 was the most effective between chronic gastritis and GC. The gbm model with 14 autoantibodies had the highest Youden's index for GC versus controls, and a 13-autoantibody model performed best for GC versus all gastritis. Conclusions: Specific panels of autoantibodies could serve as noninvasive diagnostic tools for distinguishing GC from controls and gastritis.

The coronavirus disease 2019 (COVID‐19) pandemic is an ongoing global public health crisis. The causative agent, the SARS‐CoV‐2 virus, enters host cells via molecular interactions between the viral spike protein and the host cell ACE2 surface protein. The SARS‐CoV‐2 spike protein is extensively decorated with up to 66 N‐linked glycans. Glycosylation of viral proteins is known to function in immune evasion strategies but may also function in the molecular events of viral entry into host cells. Here, we show that N‐glycosylation at Asn331 and Asn343 of SARS‐CoV‐2 spike protein is required for it to bind to ACE2 and for the entry of pseudovirus harboring the SARS‐CoV‐2 spike protein into cells. Interestingly, high‐content glycan binding screening data have shown that N‐glycosylation of Asn331 and Asn343 of the RBD is important for binding to the specific glycan molecule G4GN (Galβ−1,4 GlcNAc), which is critical for spike‐RBD‐ACE2 binding. Furthermore, IL‐6 was identified through antibody array analysis of conditioned media of the corresponding pseudovirus assay. Mutation of N‐glycosylation of Asn331 and Asn343 sites of the spike receptor‐binding domain (RBD) significantly reduced the transcriptional upregulation of pro‐inflammatory signaling molecule IL‐6. In addition, IL‐6 levels correlated with spike protein levels in COVID‐19 patients' serum. These findings establish the importance of RBD glycosylation in SARS‐CoV‐2 pathogenesis, which can be exploited for the development of novel therapeutics for COVID‐19.

The novel coronavirus (SARS‑CoV‑2) appeared in2019 in Wuhan, China, and rapidly developed into a global pandemic. The disease has affected not only health care systems and economies worldwide but has also changed the lifestyles and habits of the majority of the world's population. Among the potential targets for SARS‑CoV‑2 therapy, the viral spike glycoprotein has been studied most intensely, due to its key role in mediating viral entry into target cells and inducing a protective antibody response in infected individuals. In the present manuscript the molecular mechanisms that are responsible for SARS‑CoV‑2 infection are described and a progress report on the status of SARS‑CoV‑2 research is provided. A brief review of the clinical symptoms of the condition and current diagnostic methods and treatment plans for SARS‑CoV‑2 are also presented and the progress of preclinical research into medical intervention against SARS‑CoV‑2 infection are discussed.

Orf virus (ORFV) is a favorable oncolytic viral carrier in research, and ORFV strain NZ2 has been revealed to have antitumor effects in animal models mediated by immunoregulation profile. However, the antitumor effects triggered by the ORFV in colorectal cancer (CRC) cells is poorly characterized. The in vivo and in vitro roles of ORFV in CRC were determined using western blotting, colony formation, CCK‑8, wound scratch assay, qPCR, and animal models. Furthermore, cytokine antibody chip assay, flow cytometry, western blotting, and immunohistochemical (IHC) assays were conducted to explore the potential mechanism of ORFV. The present data revealed that ORFV strain NA1/11 infected and inhibited the in vitro growth and migration of CRC cells. By establishing a CRC model in Balb/c mice, it was revealed that ORFV strain NA1/11 significantly inhibited the in vivo growth and migration of CRC cells. A cytokine antibody array was utilized to obtain a more comprehensive profile revealing the differentially expressed cytokines in ORFV infection. Cytokines, such as IL‑7, IL‑13, IL‑15, CD27, CD30, pentraxin 3, and B lymphocyte chemoattractant (BLC), were upregulated. Axl, CXCL16, ANG‑3, MMP10, IFN‑γ R1 and VEGF‑B were downregulated. The results indicated that ORFV played roles in the regulation of key factors relevant to apoptosis, autoimmunity/inflammation, angiogenesis, and the cell cycle. Finally, data was presented to validate that ORFV infection induces oncolytic activity by enhancing apoptosis in vivo and in vitro. In conclusion, ORFV could be an oncolytic virus for CRC therapy.

Orf is one of the most widespread viral diseases worldwide, usually benign and self-limiting, and mainly affects not only sheep and goats, but also various other ruminants and mammals. The causative agent, orf virus (ORFV) is a member of the genus parapoxvirus, owing to its zoonotic importance and ability to cross-infect other species sporadically. ORFV encodes virulence and immunomodulatory factors that interfere with host inflammatory effect and antiviral immune mechanisms and induces a transient and complex cytokine response, initially represented by Th1-related cytokines followed by Th2-related cytokines. The ORFV has evolved several mechanisms to survive in the presence of the immune system, resulting in repeated infections. Currently, ORFV has been developed as vaccines in veterinary field. The unique host immune escape ability obtained by ORFV has made it one of the important candidates for prevention and treatment of various diseases (including chronic viral diseases, tumor, and liver fibrosis).

Summary: The orf virus (ORFV) is a zoonotic, epitheliotropic, DNA parapoxvirus that infects principally sheep and goats. Exposure of animals to the virus or immunization by an ORFV preparation can accentuate the severity of disease, which has provoked an interest in the underlying cellular, virological, and molecular mechanisms. The identified ORFV virulence genes and the fact that the virus can repeatedly infect a host, owing to its evasive mechanisms, contribute to the development of potent immune modulators in various animal species. ORFV has been developed as a vaccine in veterinary medicine. The unique host immune‐evasion ability of ORFV has made it an important candidate for vaccine vectors and biological agents (as an oncolytic virus). Genetic modifications using ORFV to obtain safe and efficient preparations and mechanistic studies are improvements to the currently available methods for disease treatment.