A series of clinical trials have confirmed the correlation between vascular calcification (VC) and cardiovascular events and mortality. However, current treatments have little effects on the regression of VC. Potent and illustrative mechanisms have been proven to exist in both bone metabolism and VC, indicating that these two processes share similarities in onset and progression. Multiple osteoblast-like cells and signaling pathways are involved in the process of VC. In this review, we summarized the roles of different osteoblast-like cells and we emphasized on how they communicated and interacted with each other using different signaling pathways. Further studies are needed to uncover the underlying mechanisms and to provide novel therapies for VC.

Estrogen receptor–negative (ER-negative) breast cancer is thought to be more malignant and devastating than ER-positive breast cancer. ER-negative breast cancer exhibits elevated NF-κB activity, but how this abnormally high NF-κB activity is maintained is poorly understood. The importance of linear ubiquitination, which is generated by the linear ubiquitin chain assembly complex (LUBAC), is increasingly appreciated in NF-κB signaling, which regulates cell activation and death. Here, we showed that epsin proteins, a family of ubiquitin-binding endocytic adaptors, interacted with LUBAC via its ubiquitin-interacting motif and bound LUBAC’s bona fide substrate NEMO via its N-terminal homolog (ENTH) domain. Furthermore, epsins promoted NF-κB essential modulator (NEMO) linear ubiquitination and served as scaffolds for recruiting other components of the IκB kinase (IKK) complex, resulting in the heightened IKK activation and sustained NF-κB signaling essential for the development of ER-negative breast cancer. Heightened epsin levels in ER-negative human breast cancer are associated with poor relapse-free survival. We showed that transgenic and pharmacological approaches eliminating epsins potently impeded breast cancer development in both spontaneous and patient-derived xenograft breast cancer mouse models. Our findings established the pivotal role epsins played in promoting breast cancer. Thus, targeting epsins may represent a strategy to restrain NF-κB signaling and provide an important perspective into ER-negative breast cancer treatment.

Background: Skin cutaneous melanoma (SKCM) is one of most aggressive type of cancers worldwide. Serglycin (SRGN) is an intracellular proteoglycan that playing an important role in various tumors. However, its effect on immune infiltrates and whether it associates with survival of SKCM and SKCM-metastasis patients has not been explored. Methods: We evaluated SRGN expression via the databases of Oncomine, Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). The influence of SRGN expression on survival of SKCM and SKCM-metastasis patients was analyzed using TIMER database. Furthermore, the correlations between SRGN expression and immune infiltrates or gene marker sets of immune infiltrates were also analyzed via TIMER database. Results: We found that the expression of SRGN in SKCM and SKCM-metastasis tissues was significantly increased compared to the normal skin tissues (P < 0.001). Interestingly, it was showed that lower level of SRGN expression and lower immune infiltrates of B cell, CD8+ T cell, Neutrophil, and Dendritic cell were correlated with poor survival rate of SKCM and SKCM-metastasis patients (P < 0.001) but not SKCM primary patients. We also demonstrated that SRGN expression was positively associated with the immune infiltrates and diverse immune marker sets in SKCM and SKCM-metastasis. Conclusions: Our findings indicated that SRGN was associated with the survival of SKCM and SKCM-metastasis patients. SRGN may be a new immune therapy target for treating SKCM and SKCM-metastasis.

The coronary reperfusion following acute myocardial infarction can paradoxically trigger myocardial ischemia-reperfusion (IR) injury. This complex phenomenon involves the intricate interplay of different subsets of macrophages. These macrophages are crucial players in the post-infarction inflammatory response and subsequent myocardial anti-inflammatory repair. However, their diverse functions can lead to both beneficial and detrimental effects. On one hand, these macrophages play a crucial role in orchestrating the inflammatory response, aiding in the clearance of cellular debris and initiating tissue repair mechanisms. On the other hand, their excessive infiltration and activation can contribute to the perpetuation of the inflammatory cascade, leading to additional myocardial injury and adverse cardiac remodeling. Multiple mechanisms contribute to the IR injury mediated by macrophages, including oxidative stress, apoptosis, and autophagy. These processes further exacerbate the damage to the already vulnerable myocardial tissue. To address this delicate balance, therapeutic strategies aiming to target and modulate macrophage polarization and function are being explored. By fine-tuning the immune inflammatory response, such interventions hold promise in mitigating post-infarction myocardial injury and fostering a more favorable environment for myocardial healing and recovery. Through advancements in this area of research, potential anti-inflammatory interventions may pave the way for improved clinical outcomes and better management of patients after acute myocardial infarction.

Background: Arterial calcification is a significant cardiovascular risk factor in hemodialysis patients. A series of factors are involved in the process of arterial calcification; however, the relationship between malnutrition and arterial calcification is still unclear. Methods: 68 hemodialysis patients were enrolled in this study. Nutrition status was evaluated using modified quantitative subjective global assessment (MQSGA). Related serum biochemical parameters were measured. And the radial artery samples were collected during the arteriovenous fistula surgeries. Hematoxylin/eosin stain was used to observe the arterial structures while Alizarin red stain to observe calcified depositions and classify calcified degree. The expressions of bone morphogenetic protein 2 (BMP2) and matrix Gla protein (MGP) were detected by immunohistochemistry and western blot methods. Results: 66.18% hemodialysis patients were malnutrition. In hemodialysis patients, the calcified depositions were mainly located in the medial layer of the radial arteries and the expressions of BMP2 and MGP were both increased in the calcified areas. The levels of serum albumin were negatively associated with calcification score and the expressions of BMP2 and MGP. While MQSGA score, serum phosphorus and calcium × phosphorus product showed positive relationships with calcification score and the expressions of BMP2 and MGP. Conclusions: Malnutrition is prevalent in hemodialysis patients and is associated with arterial calcification and the expressions of BMP2 and MGP in calcified radial arteries. Malnutrition may be a new inducer candidate for arterial calcification in hemodialysis patients.