The specificities, influencing factors, and medical implications of bone circadian rhythms.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

Clinical application of calcium silicate-based bioceramics in endodontics.

Pulp treatment is extremely common in endodontics, with the main purpose of eliminating clinical symptoms and preserving tooth physiological function. However, the effect of dental pulp treatment is closely related to the methods and materials used in the process of treatment. Plenty of studies about calcium silicate-based bioceramics which are widely applied in various endodontic operations have been reported because of their significant biocompatibility and bioactivity. Although most of these materials have superior physical and chemical properties, the differences between them can also have an impact on the success rate of different clinical practices. Therefore, this review is focused on the applications of several common calcium silicate-based bioceramics, including Mineral trioxide aggregate (MTA), Biodentine, Bioaggregate, iRoot BP Plus in usual endodontic treatment, such as dental pulp capping, root perforation repair, regenerative endodontic procedures (REPs), apexification, root-end filling and root canal treatment (RCT). Besides, the efficacy of these bioceramics mentioned above in human trials is also compared, which aims to provide clinical guidance for their clinical application in endodontics.

LncRNA MIR4435-2HG suppression regulates macrophage M1/M2 polarization and reduces intestinal inflammation in mice with ulcerative colitis.

OBJECTIVE: To explore the effect and potential mechanism of LncRNA MIR4435-2HG on macrophage polarization and intestinal inflammation in ulcerative colitis (UC). Methods RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) were co-cultured with Caco-2 cells to establish an inflammatory model of UC in vitro. Balb/c mice were orally administered dextran sulfate sodium (DSS) to establish an in vivo UC model. Flow cytometry and immunohistochemical (IHC) analyses were performed to assess the levels of surface phenotype markers. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed to measure the levels of inflammatory cytokines. Western blotting was used to analyze expression of the tight junction protein zona occludens 1 (ZO-1) and the key proteins of the JAK1/STAT1 signaling pathway (Janus kinase-1(JAK1), p-JAK1, signal transducer and activator of transcription 1 (STAT1), p-STAT1. Results In in vitro experiments, we found that inhibition of MIR4435-2HG was able to decrease the levels of CD68, iNOS, IL-6, and TEER, and increase the levels of CD206, Arg-1, IGF-1, and ZO-1. Meanwhile, inhibition of MIR4435-2HG significantly suppressed the levels of p- JAK1 and p- STAT1. In addition, we further demonstrated by in vivo experiments that inhibition of MIR4435-2HG significantly attenuated intestinal inflammation in mice, as evidenced by increased body weight, increased colon length and weight, decreased fecal scores, hemorrhagic scores, and DAI scores, and amelioration of colonic injury, and decreased inflammatory factors. Conclusions MIR4435-2HG suppression inhibits macrophage M1 polarization while promoting M2 polarization, thereby alleviating intestinal inflammation in mice with ulcerative colitis through JAK1/STAT1 signaling.

Interaction between apical periodontitis and systemic disease (Review).

Apical periodontitis is an oral common inflammatory disease initiated by infection of pulp chamber and is characterized by destruction and resorption of the periapical bone. As a local infection, pathogens and their products in periapical tissues, as well as inflammatory cytokines produced in periapical lesions, enter the blood circulation, triggering systemic immune responses and leading to the pathogenesis of various types of systemic disease. Therefore, apical periodontitis might be associated with systemic disease rather than solely simple local oral disease. In addition, the existence of a hyperinflammatory state in certain patients with chronic inflammation­related disorder may affect the progression or prognosis of apical periodontitis. However, the association and potential mechanisms between apical periodontitis and systemic diseases remain unclear. An in­depth understanding of the association between apical periodontitis and systemic disease will be useful for both dentists and physicians to eliminate the possible risk factors and promote the healing of apical periodontitis and systemic disease. Thus, the aim of the present review is to introduce the potential relationship between apical periodontitis and systemic disease.

Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis.

OBJECTIVE: Endothelial regeneration is an essential process for the prevention of excessive neointimal formation following endothelial denudation. Beclin 1, a mammalian autophagy gene, is a link between autophagy and apoptosis. We hypothesized that the interference of Beclin 1 can influence re-endothelialization and ultimately affect neointimal formation by regulating autophagy and apoptosis. METHODS: A rat carotid injury model of endothelial denudation was used, and small interfering RNA of Beclin 1 was perivascularly administered. Neointima was evaluated by morphological analysis. von Willebrand factor, Beclin 1, LC3, autophagic substrate p62 and caspase-3 levels were detected by immunofluorescence or Western blotting. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling assay was performed to evaluate apoptosis. RESULTS: Carotid injury induced an upregulation of Beclin 1 protein which was down regulated by more than 50% with small RNA interference. Beclin 1 knockdown significantly retarded re-endothelialization 7 days after injury and subsequently augmented neointima by more than 2 folds at 14 and 21 days. Autophagy and apoptosis were detected to reveal the regulatory effect of Beclin 1. The injury-activated autophagy, shown by the increased levels of punctate LC3 and LC3II as well as decreased p62 expression, was significantly inhibited by Beclin 1 knockdown. Meanwhile, the apoptotic endothelial cell number was increased and caspase-3 was up-regulated, though the expression of truncated BID was not significantly influenced. CONCLUSION: Beclin 1 knockdown exacerbated neointimal formation after rat carotid injury, associated with retarded re-endothelialization due to enhanced apoptosis, while simultaneously prohibiting autophagic activation. The data suggested an essential role of Beclin 1 as a regulator between autophagy and apoptosis in the setting of neointimal formation.

Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.

Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.