Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Wnt3a-Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core-Shell Nanocomposite Promotes the Regeneration of Dentin-Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells.

Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a-HANW@MpSi) core-shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a-HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a-HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin-pulp complex-like tissues and blood vessels by Wnt3a-HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a-HANW@MpSi in treatments of dental pulp exposure.

Advanced thymic lymphoepithelioma-like carcinoma with bone marrow metastases treated by immunotherapy combined with antiangiogenesis therapy: a case report.

Thymic lymphoepithelioma-like carcinoma (LELC) is a rare primary malignant neoplasm originating from the thymus. Thymic LELC diagnosis is often terminal when diagnosed, some patients have lost the opportunity for surgery. Platinum- and anthracycline-based systemic chemotherapy are the first-line treatment plan; however, there is no clear consensus on therapy when first-line treatment fails because of the lack of cases of advanced thymic LELC. Here was a rare case of advanced thymic LELC with bone marrow metastasis at relapse, which is reported in a patient who responded well to toripalimab combined with anlotinib therapy. The treatment showed tolerable toxicity with good antitumor activity in the patient. As far as we know, this is the first case that the combination of toripalimab with anlotinib is effective in controlling advanced thymic LELC with bone marrow metastasis. The case reports represent an essential means by which an effective therapy for advanced thymic LELC may not be practical given the low frequency of a thymic LELC with multiple metastases.

[Satisfaction and clinical assessment of 56 adult patients with biofunctional complete denture].

PURPOSE: The purpose of this study was to investigate the patient satisfaction and the clinical effect of biofunctional complete denture via questionnaire survey. METHODS: Fifty-six patients(26 males and 30 females) with biofunctional complete denture were asked to fill in a questionnaire about satisfaction and the type-variety of food after repair for 1 week, 1 month and 3 months during regular follow-up visits or telephone visits. SPSS 26.0 software package was used to analyze the data. RESULTS: After 3 months of wearing bio-functional complete denture, the average score of the five indicators of aesthetic degree, speech function, chewing function, retention function and comfort level of the patients were >6, reaching the level of "satisfactory" or "fair"; among which the aesthetic degree was the highest (7.71±1.46). The food type score reached 33.96±1.21 at the third month. Repeated measures ANOVA showed that each group of indexes changed significantly over time (P<0.05). Except that the mean value of aesthetics score was equal at 3 months and 6 months, the other indexes all increased along time. Among 56 patients, two had 5 or more times of modification due to pain, accounting for 3.57%. CONCLUSIONS: Bio-functional complete denture can achieve good clinical effect in the early stage of denture repair in patients with dentition loss.

Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo.

PURPOSE: Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo. METHODS: We established a hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot. RESULTS: We successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased. CONCLUSION: We partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo.

A Clinical Observation of Thymic Epithelial Tumor Metastatic to Breast.

BACKGROUND: Thymic carcinoma is prone to early metastasis and invasion, while its metastasis to the breast is particularly unique. CASE REPORT: We describe a case of thymic epithelial tumor metastatic to the breast fulfilling clinical diagnostic criteria. A 47-year-old female patient diagnosed with stage IV thymic carcinoma and previously treated with chemoradiation was diagnosed with metastatic breast cancer during a periodic review. Color Doppler ultrasonography showed a low-echo real occupancy in the breast. Pathological examination of the breast mass confirmed the diagnosis of thymic carcinoma metastasis. CONCLUSION: Hematogenous metastasis of thymic carcinoma to the breast is rare but not exceptional, and long-term survival can be expected with appropriate treatment.