Lung cancer remains the leading cause of cancer-related mortality worldwide. In advanced lung cancer stages, bone metastasis is rampant and significantly reduces the quality of life of patients. Members of the semaphorin family, particularly semaphorin 3A (SEMA3A), have been implicated in lung cancer growth and metastasis; however, their role remains unclear. In this study, we investigated the relationship between SEMA3A signaling and microRNA (miRNA) regulation in a highly bone metastatic lung cancer cell line (HARA-B4). Microarray analysis and qRT-PCR revealed upregulation of miR-20b-5p expression in SEMA3A knockdown cells. Target pathway analysis identified cyclin D1(CCND1), a key regulator of cell cycle progression, as the downstream target. miR-20b-5p mimic reduced CCND1 expression and suppressed cell proliferation in HARA-B4. These findings suggest that SEMA3A-dependent tumor growth is mediated by the increased CCND1 expression resulting from reduced miR-20b-5p expression. Understanding the dual roles of SEMA3A and miR-20b-5p may provide potential therapeutic and diagnostic avenues for treating metastatic bone lung cancer.

This study examined the root canal morphology and the incidence of accessory root canals in mandibular central incisors, factors believed to influence the success of root canal treatment. Micro-computed tomography scans were conducted on Japanese mandibular central incisors from the Department of Anatomy collection at Tokyo Dental College. Morphological types were classified according to Vertucci’s system, and the presence of accessory root canals was analyzed based on three-dimensional reconstructions. All examined incisors were found to have single roots. When classified by the number of main root canals, 87% were Type I with a single complete root canal, and 10% were Type III, with a single root canal splitting into two and then fusing again, figures generally consistent with those of previous reports. Types IV and VII, with a lingual root canal, were also present, though at low frequencies. The incidence of accessory root canals was 36.0%, a higher rate than previously reported. An investigation of the shape of the root canal in cross-section showed that, in the horizontal plane perpendicular to the tooth axis at a distance of 9 mm from the apex (A plane), the circular shape was the most common, whereas in the horizontal plane perpendicular to the tooth axis at a distance of 6 mm from the apex (B plane), the oval shape was the most common, and the dumbbell shape was also seen in the horizontal plane perpendicular to the tooth axis at a distance of 3 mm from the apex (C plane). These results suggest that, although the root canal morphology of the mandibular central incisors is usually simple, the possibility that some main root canals may be difficult to clean and that an accessory root canal may be present should be borne in mind when carrying out pulp chamber enlargement and root canal treatment.

Osteoarthritis (OA) is a prevalent joint disorder characterized by the degradation of the extracellular matrix (ECM), destruction of cartilage and bone, and chronic inflammation. Diallyl disulfide (DADS), recognized for its anti-inflammatory, antioxidant, and anti-apoptotic properties, has not been previously assessed in the context of OA. This study aimed to explore the protective effects of DADS on lipopolysaccharide (LPS)-induced chondrocyte apoptosis, cartilage degeneration, and inflammation, as well as its underlying molecular mechanisms. Human chondrocytes were cultured in vitro, and an OA model was established through LPS stimulation. Various concentrations of DADS were analyzed to examine cell viability, apoptosis, ECM-related protein expression, levels of inflammatory cytokines, NLRP3 inflammasome activation, and NF-κB signaling. The results demonstrated that DADS alleviated LPS-induced chondrocyte injury and ECM degradation, suppressed inflammation and NLRP3 inflammasome activation, and inhibited LPS-induced NF-κB activation. Further analysis revealed that Nrf2 could play a crucial role in the protective effects of DADS against LPS-induced chondrocytes, in which DADS treatment activated the Nrf2/HO-1 pathway, and Nrf2 knockdown neutralized the protective effects of DADS. In conclusion, DADS could mitigate LPS-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation by activating the Nrf2/HO-1 signaling pathway in chondrocytes and simultaneously inhibiting the NF-κB signaling pathway and NLRP3 inflammasome activity. This research provided a promising therapeutic strategy for diseases associated with chondrocyte injury.

The aim of this study was to investigate the expression of melanoma inhibitory activity (MIA) and MIA2 in oral squamous cell carcinoma (OSCC) primary tumor (PT) and lymph node metastasis (LNM) specimens and clarify its usefulness in predicting LNM. The expression of MIA and MIA2 was evaluated using immunohistochemistry in a total of 122 paraffin-embedded OSCC PT and 40 LNM specimens. Expression of MIA and MIA2 was observed in the cytoplasm of PT and LNM tumor cells. In PTs, MIA expression was significantly increased in cases with LNM (LNM-positive vs. LNM-negative, p=0.016). MIA2 expression tended to be higher in cases with LNM (LNM-positive vs. LNM-negative, p=0.080). The expression of both MIA and MIA2 was significantly upregulated in LNM specimens than in PTs (MIA, p=0.002; MIA2, p=0.013), and MIA expression was significantly higher in cases with extranodal extension (p=0.026). These results suggest that the expression of both MIA and MIA2 is increased in cases with LNM; thus, MIA and MIA2 may be useful markers for predicting LNM in OSCC.

Bone density is an important parameter for successful dental implant treatment. As a preoperative evaluation before implant placement, computed tomography (CT) scan is performed to determine bone volume and density. The Misch bone density classification is based on two criteria: (1) tactile sensation during implant site drilling and (2) CT value expressed in Hounsfield units (HU). The classification categories gradually decrease in HU, from D1 (>1250 HU) to D5 (<150 HU). In experimental studies, bovine bone has been used to investigate primary stability, implant geometry, and surgical techniques. However, a detailed study on the correlation between bone density and trabecular bone structure has not been reported in bovine bone. This study aimed to verify the correlation between bone density classification by CT value and the trabecular bone structure on bovine bone. Fifteen sites of D2-D5 from bovine bones were selected using multidetector CT scan. Histological evaluation was performed, and the bone area ratio, expressed as a percentage of the bone area within the region of interest, was calculated. The bone area ratio differed significantly between each pair of Misch classification (p < 0.05), except for D3 and D4. The CT value and bone area ratio showed a significant positive correlation (r = 0.92, p < 0.05). This result suggests that the evaluation of bone density by CT value is related to its histological structure.

Hydroxyapatite (HAp) is widely used as an artificial bone graft material in orthopedic and dental surgeries because of its excellent biocompatibility. However, the slow biodegradation rate of HAp scaffolds can increase the risk of infection at implanted sites and hinder bone tissue regeneration. Carbonated apatite (CA), which is a substituted HAp with carbonate ions replaced by phosphate ions in the HAp lattice, has been demonstrated to exhibit higher solubility than that exhibited by HAp. Therefore, this study investigated porous CA-based blocks fabricated by sintering a mixture of CA powder and organic beads. The synthesized CA, identified as B-type CA, had a carbonate content of 8%, which is close to that present in natural bones. The fabricated CA block, with over 60% porosity, promoted osteoblast activity and new bone formation within the pores. The porous CA blocks were implanted into the holes/defects created at different sites in the rabbit femur, and the in vivo behavior of the porous CA blocks was compared with that of the porous HA blocks. At one and three months after implantation, changes in the blocks and new bone formation were observed in different sites—cortical, cancellous, and bone marrow. At three months post-implantation, the HAp block hardly dissolved, whereas the implanted CA block dissolved in the cancellous bone and bone marrow, which have high blood flow. Additionally, at three months post-implantation, the CA blocks exhibited superior bone formation in the cortical bone and similar bone growth as compared to that exhibited by the HAp blocks. This study demonstrates that porous CA blocks are suitable alternatives to porous HAp blocks for use as bone scaffolds because of their superior osteoconductivity and biosolubility.

Living cells are subjected to various biomechanical stimuli from their local microenvironments. The information transforms into intracellular biochemical signals, and the stimulus induces a change in cell behaviors. Electrical stimulation is known to affect bone formation; in particular, in vivo studies have shown that hydroxyapatite (HAp) electret stimulation could enhance bone formation. However, the molecular mechanisms underlying the electret-induced influences on osteogenic cells have not been clarified. In this study, we investigated the molecular mechanotransduction cascade that mediates the cell responses to the electric stimuli produced by the electret in order to regulate its safe application in a clinical setting. The HAp electret was fabricated to be applied through a DC field on HAp at high temperature to enhance proton conduction in the HAp lattice. Osteoblast-like cells were cultured on the electret, which induced cell adhesion and proliferation responses. In addition, the adaptor protein p130Cas (Cas), a known mechanosensor protein, sensed the electret-induced stimuli and activated a downstream signal cascade involving extracellular signal-regulated kinase (ERK). Entry to the S-phase of the cell cycle was subsequently promoted. Further, activation of Cas and ERK was maintained throughout the cell culture period. These results likely arise from the interactions between osteoblasts and the HAp electret, whose surface charges and electrostatic generator function are assumed to function in promoting cell adhesion and proliferation under static dynamic conditions, respectively. Thus, HAp electret-induced stimuli are beneficial for enhancing osteoblast proliferation, suggesting that an electret could be a maintenance-free bone substitute to promote bone regeneration.

This study mainly observed the inhibitory effect of 6% hydroxyethyl starch 130/0.4 (HES) on the apoptosis of RAW264.7 cells induced by lipopolysaccharide (LPS) and its effect on the peroxisome proliferator-activated receptor coactivator-1α. Screening the concentration of HES by CCK-8; Determination of target genes of HES by gene chip technology. Cell experiments were divided into Control group, LPS group, HES group and PGC-1α-shRNA group. The growth activity of cells in each group was detected by CCK-8 method and the apoptosis rate of cells in each group was detected by flow cytometry. Rh123 staining was used to detect the membrane potential of mitochondria in each group Western blot was used to detect PGC-1α, nuclear respiratory factor 1 (NRF1) and NRF2, OpticAtrophy1 (OPA1) and mitochondrial outer membrane fusion protein 2 (mitofusin2, MFN2) and the expression of B cell lymphoma-2 (Bcl-2) and Bcl-2 related X protein (Bax). The concentration of HES was (30 mg/mL). It was verified by gene chip and PCR that the target of HES was PGC-1α; Compared with the cells in Control group, the growth activity, mitochondrial membrane potential, expressions of PGC-1α, NRF2, NRF1, OPA1, MFN2 and Bcl-2 in LPS group, HES group and PGC-1α-shRNA group decreased significantly, while the apoptosis rate and the expression of Bax in cells increased significantly. Compared with the cells in LPS group, the growth activity, mitochondrial membrane potential, the expressions of PGC-1α, NRF2, NRF1, OPA1, MFN2 and Bcl-2 in HES group and PGC-1α-shRNA group increased significantly, while the apoptosis rate and the expression of Bax in cells decreased significantly. Compared with HES cells, the growth activity of PGC-1α-shRNA cells, the membrane potential of mitochondria, the expressions of PGC-1α, NRF2, NRF1, OPA1, MFN2 and Bcl-2 in cells decreased significantly, and the apoptosis rate and the expression of Bax in cells increased significantly, with statistical significance (all P<0.05). 6% hydroxyethyl starch 130/0.4 (HES) could regulate the expression of PGC-1α, enhance the biosynthesis of mitochondria in cells, and inhibit the apoptosis of RAW264.7 cells induced by LPS.

Currently available treatments for osteoporosis suppress bone resorption and formation, which can lead to complications such as atypical femoral fracture. Although the Kampo medicine Boi-ogi-to (BOT), a traditional prescription, has been used clinically to treat arthritis and obesity, no study has examined its efficacy in estrogen deficiency induced postmenopausal osteoporosis. Consequently, the present study was designed to examine whether BOT exerts beneficial effects on bone in an ovariectomized (OVX) mice model of postmenopausal osteoporosis compared with bazedoxifene (BAZ). Six-week-old female mice underwent ovariectomy, and were randomized into the sham control, OVX control, OVX + BOT (600 mg/kg/day), and OVX+BAZ (0.5 mg/kg/day) groups after 2 weeks. After 30 weeks of treatment, histomorphometric analysis of the tibia and gene expression analyses of the femur were performed, and serum biochemical markers were examined. The results suggested that treatment with BOT or BAZ increased trabecular bone volume and thickness and improved bone structural parameters of the tibia in OVX mice. OVX mice treated with BAZ resulted exhibited a significant decrease in bone resorption and bone formation. Whereas OVX mice treated with BOT exhibited inhibited bone resorption, with no marked effect on bone formation. Changes in serum biochemical markers, osteocalcin and tartrate-resistant acid phosphatase-5b provided similar evidence. Thus, the present study demonstrated that BOT suppresses bone resorption induced by estrogen deficiency and improved trabecular bone microstructure in OVX mice.