Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.

Ym1 is a rodent-specific chitinase-like protein (CLP) lacking catalytic activity, whose cellular origins are mainly macrophages, neutrophils and other cells. Although the detailed function of Ym1 remains poorly understood, Ym1 has been generally recognized as a fundamental feature of alternative activation of macrophages in mice and hence one of the prevalent detecting targets in macrophage phenotype distinguishment. Studies have pointed out that Ym1 may have regulatory effects, which are multifaceted and even contradictory, far more than just a mere marker. Allergic lung inflammation, parasite infection, autoimmune diseases, and central nervous system diseases have been found associations with Ym1 to varying degrees. Thus, insights into Ym1’s role in diseases would help us understand the pathogenesis of different diseases and clarify the genuine roles of CLPs in mammals. This review summarizes the information on Ym1 from the gene to its expression and regulation and focuses on the association between Ym1 and diseases.

Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis. We hypothesize that Pkm2, as a key regulatory enzyme of glycolysis pathway, triggers the activation of macrophages (Mφ), which results in proinflammatory cytokine production during the arthritis progress. In this study, Pkm2 was found to be overexpressed in ED1-positive Mφ in spleens and synovial tissues from arthritic rats via immunofluorescence, Western blotting, and quantitative RT-PCR. To reveal the role of Pkm2, Dark Agouti rats were treated with either Pkm2 enzyme inhibitor shikonin or the RNA interference plasmids of Pkm2 and negative control plasmids, respectively, via i.p. injection. Pkm2 intervention could alleviate the severity of pristane-induced arthritis in aspects of the macroscopic arthritis score, perimeter changes of midpaw, and the synovitis and destruction of the bone and cartilage as well as reduce the ED1 and p-Stat1–positive cell population in rat synovial tissues. Silencing Pkm2 by RNA interference in classical activated rat and mouse Mφ resulted in less Tnf-α, Il-1β production via Stat1 signaling. Collectively, Pkm2 is highly expressed in ED1-positive Mφ of spleens and synovial tissues from arthritic rats and promotes Mφ activation via Stat1 signaling. Pkm2 might be a promising selective metabolic target molecule for rheumatoid arthritis treatment.

We have positionally cloned the Ym1 gene, with a duplication and a promoter polymorphism, as a major regulator of inflammation. Mice with the RIIIS/J haplotype, with the absence of Ym1 expression, showed reduced susceptibility to mannan-enhanced collagen antibody–induced arthritis and to chronic arthritis induced by intranasal exposure of mannan. Depletion of lung macrophages alleviated arthritis, whereas intranasal supplement of Ym1 protein to Ym1-deficient mice reversed the disease, suggesting a key role of Ym1 for inflammatory activity by lung macrophages. Ym1-deficient mice with pneumonitis had less eosinophil infiltration, reduced production of type II cytokines and IgG1, and skewing of macrophages toward alternative activation due to enhanced STAT6 activation. Proteomics analysis connected Ym1 polymorphism with changed lipid metabolism. Induced PPAR-γ and lipid metabolism in Ym1-deficient macrophages contributed to cellular polarization. In conclusion, the natural polymorphism of Ym1 regulates alternative activation of macrophages associated with pulmonary inflammation.

Background: The musculoskeletal toxicity of immune checkpoint inhibitors (ICIs) is receiving increasing attention with clinical experience. Nevertheless, the absence of a systematic investigation into the musculoskeletal toxicity profile of ICIs currently results in the under-recognition of associated adverse events. Further and more comprehensive investigations are warranted to delineate the musculoskeletal toxicity profile of ICIs and characterize these adverse events.Material and methods: The present study employed the FDA Adverse Event Reporting System database to collect adverse events between January 2010 and March 2021. We utilized both the reporting odds ratio and the Bayesian confidence propagation neural network algorithms to identify suspected musculoskeletal adverse events induced by ICIs. Subsequently, the clinical characteristics and comorbidities of the major musculoskeletal adverse events were analyzed. The risk of causing these events with combination therapy versus monotherapy was compared using logistic regression model and Ω shrinkage measure model.Results: The musculoskeletal toxicity induced by ICIs primarily involves muscle tissue, including neuromuscular junctions, fascia, tendons, and tendon sheaths, as well as joints, spine, and bones, including cartilage. The toxicity profile of PD-1/PD-L1 and CTLA-4 inhibitors varies, wherein the PD-1 inhibitor pembrolizumab exhibits a heightened overall risk of inducing musculoskeletal adverse events. The major ICIs-induce musculoskeletal adverse events, encompassing conditions such as myositis, neuromyopathy (including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Guillain-Barré syndrome, and Chronic inflammatory demyelinating polyradiculoneuropathy), arthritis, fractures, myelitis, spinal stenosis, Sjogren’s syndrome, fasciitis, tenosynovitis, rhabdomyolysis, rheumatoid myalgia, and chondrocalcinosis. Our study provides clinical characteristics and comorbidities of the major ICIs-induced musculoskeletal adverse events. Furthermore, the combination therapy of nivolumab and ipilimumab does not result in a statistically significant escalation of the risk associated with the major musculoskeletal adverse events.Conclusion: Immune checkpoint inhibitors administration triggers a range of musculoskeletal adverse events, warranting the optimization of their management during clinical practice.