In situ bone regeneration and vertical bone augmentation have been huge problems in clinical practice, always imposing a significant economic burden and causing patient suffering. Herein, MgZnYNd magnesium alloy rod implantation in mouse femur resulted in substantial subperiosteal new bone formation, with osteoimmunomodulation playing a pivotal role. Abundant macrophages were attracted to the subperiosteal new bone region and proved to be the most important regulation cells for bone regeneration. Periosteum stripping, macrophage depletion, and interleukin-10 (IL-10) blockade effectively diminished the MgZnYNd alloy-induced subperiosteal osteogenesis. Mechanistically, the degradation products of MgZnYNd alloy promoted M2 macrophage polarization and the secretion of anti-inflammatory cytokine IL-10, which enhanced periosteum-derived stem cells (PDSCs) osteogenesis through the JAK1-STAT3 pathway. An anti-IL-10 neutralizing antibody or STAT3 inhibitor significantly inhibited M2 macrophage-mediated osteogenic differentiation of PDSCs. Transcriptomics and proteomics revealed that periostin is the core regulator of PDSCs osteogenic differentiation. Furthermore, a novel clinical translation application of Mg-induced subperiosteal osteogenesis was developed, demonstrating its ability to preserve the height and width of the alveolar crest in rats and rabbits following tooth extraction. Collectively, these findings unveil a previously undefined role for Mg alloy-induced subperiosteal osteogenesis via macrophage-mediated osteoimmunomodulation, suggesting the therapeutic potential of magnesium alloy in bone regeneration and bone augmentation.

Elevated IgG expression in cancer cells has been implicated in exacerbated malignancy and poor clinical prognosis. Accumulating evidence indicates that a nonconventional sialylation modification is critical for the function of cancer-derived IgG, indicating the need for a better understanding of the regulatory mechanisms that control the expression and function of sialylated cancer IgG (SIA-cIgG). Here, we conducted genome-wide CRISPR activation screening and identified OCT4 and SOX2 as the key factors that promote SIA-cIgG expression. Functional investigation revealed that SIA-cIgG reciprocally stimulated SOX2 by activating the c-Met/Akt/Erk signaling axis, constituting a self-propagating loop of SIA-cIgG/c-Met/SOX2/SIA-cIgG signaling. This signaling loop was highly active in stem-like cells from many epithelial cancers and was crucial for cancer stemness in vitro and in vivo. Notably, the mAb RP215, which specifically recognizes the Asn162 sialylation–related epitope on SIA-cIgG, effectively blocked the SIA-cIgG–driven signaling loop. Furthermore, RP215 significantly inhibited lung cancer cell stemness and tumor growth in a patient-derived xenograft model. In conclusion, these findings revealed a self-propagating c-Met/SOX2/SIA-cIgG signaling loop that promotes cancer stemness, identifying novel therapeutic strategies for cancer treatment. Significance: Sialylated cancer IgG activates c-Met-SOX2 signaling to promote stemness properties in cancer cells and can be targeted to suppress tumor growth.

A polysaccharide named GSP-2 with a molecular size of 32 kDa was isolated from the fruiting bodies of Ganoderma sinense. Its structure was well elucidated, by a combined utilization of chemical and spectroscopic techniques, to be a β-glucan with a backbone of (1→4)– and (1→6)–Glcp, bearing terminal- and (1→3)–Glcp side-chains at O-3 position of (1→6)–Glcp. Immunological assay exhibited that GSP-2 significantly induced the proliferation of BALB/c mice splenocytes with target on only B cells, and enhanced the production of several cytokines in human peripheral blood mononuclear cells and derived dendritic cells. Besides, the fluorescent labeled GSP-2 was phagocytosed by the RAW 264.7 cells and induced the nitric oxide secretion from the cells.

Background: Pigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy.Method: In this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14⁺cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function.Results: The most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA.Conclusion: The transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.

Introduction: Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer.Methods: One hundred and thirteen patients with lung cancer and 99 age‐matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony‐stimulating factors were detected by enzyme‐linked immunosorbent assay (ELISA).Results: A reduction in antitumor NK cells (p < 0.0001) and an increase in the protumor MDSCs (p < 0.0001) were observed in the lung cancer patients compared with the controls. Monocyte counts were significantly higher in lung cancer patients with histories of smoking (p < 0.05) or drinking (p < 0.01) than in patients with no relevant history or healthy controls. The number of neutrophils and the neutrophil‐to‐lymphocyte ratio (NLR) were particularly higher in patients with liver metastasis (p < 0.01) compared with no metastasis patients or healthy controls. Levels of the monocyte‐derived cytokine interleukin‐6 (p < 0.05), granulocyte colony‐stimulating factor (G‐CSF) (p < 0.0001), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) (p < 0.0001) were higher in patients than in controls. G‐CSF levels decreased during the remission phase (p < 0.05), and positively correlated with carbohydrate antigen 19–9 (p < 0.05) and gene mutation (p < 0.05).Conclusion: Monocyte and neutrophil counts were higher in peripheral blood in lung cancer patients than in controls, especially when patients had histories of smoking, drinking, and liver metastasis. Serum levels of G‐CSF and GM‐CSF were higher in lung cancer patients, and G‐CSF levels positively correlated with disease severity.

Glycans, either alone or in complex with glycan-binding proteins, are essential structures that can regulate cell biology by mediating protein stability or receptor dimerization under physiological and pathological conditions. Certain glycans are ligands for lectins, which are carbohydrate-specific receptors. Bone is a complex tissue that provides mechanical support for muscles and joints, and the regulation of bone mass in mammals is governed by complex interplay between bone-forming cells, called osteoblasts, and bone-resorbing cells, called osteoclasts. Bone erosion occurs when bone resorption notably exceeds bone formation. Osteoclasts may be activated during cancer, leading to a range of symptoms, including bone pain, fracture, and spinal cord compression. Our understanding of the role of protein glycosylation in cells and tissues involved in osteoclastogenesis suggests that glycosylation-based treatments can be used in the management of diseases. The aims of this review are to clarify the process of bone resorption and investigate the signaling pathways mediated by glycosylation and their roles in osteoclast biology. Moreover, we aim to outline how the lessons learned about these approaches are paving the way for future glycobiology-focused therapeutics.