Cancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More effective and alternative inhibitory targets are critical for successful immune checkpoint blockade therapy. The interaction of the immunomodulatory ligand B7 family with corresponding receptors induces or inhibits T cell responses by sending co-stimulatory and co-inhibitory signals respectively. Blocking the glycosylation of the B7 family members PD-L1, PD-L2, B7-H3, and B7-H4 inhibited the self-stability and receptor binding of these immune checkpoint proteins, leading to immunosuppression and rapid tumor progression. Therefore, regulation of glycosylation may be the “golden key” to relieve tumor immunosuppression. The exploration of a more precise glycosylation regulation mechanism and glycan structure of B7 family proteins is conducive to the discovery and clinical application of antibodies and small molecule inhibitors.

The vascular and lymphatic systems are integral to maintaining skeletal homeostasis and responding to pathological conditions in bone and joint tissues. This review explores the interplay between blood vessels and lymphatic vessels in bones and joints, focusing on their roles in homeostasis, regeneration, and disease progression. Type H blood vessels, characterized by high expression of CD31 and endomucin, are crucial for coupling angiogenesis with osteogenesis, thus supporting bone homeostasis and repair. These vessels facilitate nutrient delivery and waste removal, and their dysfunction can lead to conditions such as ischemia and arthritis. Recent discoveries have highlighted the presence and significance of lymphatic vessels within bone tissue, challenging the traditional view that bones are devoid of lymphatics. Lymphatic vessels contribute to interstitial fluid regulation, immune cell trafficking, and tissue repair through lymphangiocrine signaling. The pathological alterations in these networks are closely linked to inflammatory joint diseases, emphasizing the need for further research into their co-regulatory mechanisms. This comprehensive review summarizes the current understanding of the structural and functional aspects of vascular and lymphatic networks in bone and joint tissues, their roles in homeostasis, and the implications of their dysfunction in disease. By elucidating the dynamic interactions between these systems, we aim to enhance the understanding of their contributions to skeletal health and disease, potentially informing the development of targeted therapeutic strategies.

Hormonal changes in pregnant and lactating women significantly affect bone metabolism and overall stress levels, positioning them as a unique group within the orthodontic population. Fluctuations in estrogen, progesterone, prolactin, and other hormones are closely linked to bone remodeling and the periodontal tissue’s response to inflammation caused by dental plaque. Hormones such as thyrotropin, leptin, and melatonin also play crucial roles in pregnancy and bone remodeling, with potential implications for orthodontic tooth movement. Additionally, adverse personal behaviors and changes in dietary habits worsen periodontal conditions and complicate periodontal maintenance during orthodontic treatment. Notably, applying orthodontic force during pregnancy and lactation may trigger stress responses in the endocrine system, altering hormone levels. However, these changes do not appear to adversely affect the mother or fetus. This review comprehensively examines the interaction between hormone levels and orthodontic tooth movement in pregnant and lactating women, offering insights to guide clinical practice.

Tumor necrosis factor‑like weak inducer of apoptosis (TWEAK)/fibroblast growth factor‑inducible 14 (Fn14) signaling represents a critical regulatory axis in tissue repair and the inflammatory response. However, the impact of TWEAK on the characteristics of periodontal ligament stem cells (PDLSCs), which subsequently influence periodontal homeostasis, remains inadequately understood. To address this, PDLSCs were isolated from human periodontitis tissue and cultured to investigate the effects of TWEAK on PDLSC proliferation, migration and osteogenic differentiation using Cell Counting Kit‑8, TUNEL, Transwell and scratch assays, and alizarin red and alkaline phosphatase staining. Transcriptome sequencing and western blot analysis were used to explore the underlying molecular mechanisms. Additionally, the potential of targeting TWEAK in periodontitis treatment was evaluated using inflammatory PDLSCs (iPDLSCs) and a rat periodontitis model. The present study demonstrated that low levels (1, 5 and 20 ng/ml) of TWEAK enhanced the proliferation and osteogenic differentiation of PDLSCs, with 1 and 5 ng/ml further enhancing their ability to promote M2 macrophage polarization. By contrast, elevated levels (100 ng/ml) of TWEAK impaired PDLSC proliferation, migration and osteogenic potential, activated the RANKL/osteoprotegerin (OPG) system, and promoted the M1 polarization of macrophages induced by PDLSCs, with the Fn14/NF‑κB pathway serving a pivotal role in this regulatory process. The expression levels of TWEAK, Fn14 and NF‑κB were significantly higher in iPDLSCs than in healthy donor‑derived PDLSCs, and these iPDLSCs exhibited reduced proliferation, migration and osteogenic potential, along with increased RANKL/OPG activation and M1 macrophage polarization. In iPDLSCs, inhibition of the TWEAK/Fn14/NF‑κB pathway enhanced cell proliferation, migration and osteogenic differentiation potential, and reversed the activation of the RANKL/OPG system and macrophage M1 polarization induced by iPDLSCs. Furthermore, high TWEAK levels were shown to accelerate the progression of rat periodontitis, while inhibition of the TWEAK/Fn14 pathway mitigated periodontitis‑induced periodontal tissue destruction in rats. Collectively, the present findings revealed the role of the TWEAK‑PDLSCs axis in the maintenance and disruption of periodontal homeostasis, and identified targeting of the TWEAK/Fn14/NF‑κB pathway in iPDLSCs during periodontitis as a promising therapeutic strategy.