Yao Jiao

Mastication exerts a significant influence on both the structural and immunological environment of the jawbone. The mechanical stress generated during chewing initiates bone remodeling through the coordinated activities of osteoclasts and osteoblasts, with these processes being modulated by immune cell responses. This review summarizes the interaction between masticatory forces and jawbone immunity, focusing on key mechanisms such as mechanotransduction in osteocytes, macrophage polarization, and the activation of T cells. The review also delves into the role of the receptor activator of nuclear factor κ-B ligand (RANKL), receptor activator of nuclear factor κ-B (RANK), and osteoprotegerin (OPG) signaling pathway, highlighting its critical function in bone resorption and immune regulation. Additionally, the review summarizes how masticatory forces modulate the immune response through changes in immune cells, particularly focusing on cytokines, and the involvement of hormonal and molecular pathways. These findings provide valuable insights into the complex interplay between mechanical forces and immune cells, with implications for bone health.

Objective: To review the effect of outer membrane vesicles (OMVs) of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis) on macrophages during periodontitis development.Method: Literature pertaining to P. gingivalis OMVs and macrophages was reviewed and discussed, with a focus on the immunomodulatory effects of P. gingivalis OMVs on macrophages.Results: P. gingivalis OMVs affect the recognition, phagocytosis, polarization, and apoptosis functions of macrophages. However, information on their antigen‐presenting effect remains lacking, and further research is required for clinical applications.Conclusion: P. gingivalis OMVs can influence the development of periodontitis through immune modulation of macrophages; however, further research is required to provide novel ideas for the prevention and treatment of periodontitis.

Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications.

Pulmonary hypertension (PH) was a cardiovascular disease with high morbidity and mortality. PH was a chronic disease with complicated pathogenesis and uncontrollable factors. PH was divided into five groups according to its pathogenesis and clinical manifestations. Although the treatment and diagnosis of PH has made great progress in the past ten years. However, the diagnosis and prognosis of the PAH had a great contrast, which was not conducive to the diagnosis and treatment of PH. If not treated properly, it will lead to right ventricular failure or even death. Therefore, it was necessary to explore the pathogenesis of PH. The problem we urgently need to solve was to find and develop drugs for the treatment of PH. We reviewed the PH articles in the past 10 years or so as well as systematically summarized the recent advance. We summarized the latest research on the key regulatory factors (pyroptosis, apoptosis, necroptosis, ferroptosis, and endoplasmic reticulum stress) involved in PH. To provide theoretical basis and basis for finding new therapeutic targets and research directions of PH.

Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family and plays a vital role in the metabolism of fatty acids. However, few studies have examined the role of FABP5 in pathological cardiac remodeling and heart failure. The aim of this study was to explore the role of FABP5 in transverse aortic constriction (TAC)-induced pathological cardiac remodeling and dysfunction in mice. Quantitative RT-PCR (qRT-PCR) and western blotting (WB) analysis showed that the levels of FABP5 mRNA and protein, respectively, were upregulated in hearts of the TAC model. Ten weeks after TAC in FABP5 knockout and wild type control mice, echocardiography, histopathology, qRT-PCR, and WB demonstrated that FABP5 deficiency aggravated cardiac injury (both cardiac hypertrophy and fibrosis) and dysfunction. In addition, transmission electron microscopy, ATP detection, and WB revealed that TAC caused severe impairment to mitochondria in the hearts of FABP5-deficient mice compared with that in control mice. When FABP5 was downregulated by siRNA in primary mouse cardiac fibroblasts, FABP5 silencing increased oxidative stress, reduced mitochondrial respiration, and increased the expression of myofibroblast activation marker genes in response to treatment with transforming growth factor-β. Our findings demonstrate that FABP5 deficiency aggravates cardiac pathological remodeling and dysfunction by damaging cardiac mitochondrial function.

In response to pathological stimuli, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. miRNAs are increasingly recognized as pathogenic factors, clinically relevant biomarkers, and potential therapeutic targets. We identified that mir15a/mir16‐1 cluster was negatively correlated with hypertrophic severity in patients with hypertrophic cardiomyopathy. The mir15a/mir16‐1 expression was enriched in cardiomyocytes (CMs), decreased in hypertrophic human hearts, and decreased in mouse hearts after transverse aortic constriction (TAC). CM‐specific mir15a/mir16‐1 knockout promoted cardiac hypertrophy and dysfunction after TAC. CCAAT/enhancer binding protein (C/EBP)β was responsible for the downregulation of mir15a/mir16‐1 cluster transcription. Mechanistically, mir15a/mir16‐1 cluster attenuated the insulin/IGF1 signal transduction cascade by inhibiting multiple targets, including INSR, IGF‐1R, AKT3, and serum/glucocorticoid regulated kinase 1 (SGK1). Pro‐hypertrophic response induced by mir15a/mir16‐1 inhibition was abolished by knockdown of insulin receptor (INSR), insulin like growth factor 1 receptor (IGF1R), AKT3, or SGK1. In vivo systemic delivery of mir15a/mir16‐1 by nanoparticles inhibited the hypertrophic phenotype induced by TAC. Importantly, decreased serum mir15a/mir16‐1 levels predicted the occurrence of left ventricular hypertrophy in a cohort of patients with hypertension. Therefore, mir15a/mir16‐1 cluster is a promising therapeutic target and biomarker for cardiac hypertrophy.