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The study aims to elucidate the mechanism through which 17β-estradiol facilitates osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). In our study, lentiviral transfection was employed to establish apoptosis repressor with caspase recruitment domain (ARC) knockdown or overexpression in BMSCs. The impact of 17β-estradiol on ARC expression was assessed using western blot, RT-PCR and immunofluorescence. Techniques such as ALP staining, ALP activity assay, western blot, RT-PCR and immunofluorescence staining were utilized to examine the influence of ARC expression levels on the osteogenic differentiation of BMSCs and the osteoclastic differentiation of Raw264.7 cell lines. Mitophagy flux levels in BMSCs were detected using the mitophagy detection kit. RNA sequencing and bioinformatics analyses were conducted to explore potential mechanisms of ARC regulation in BMSCs osteogenic differentiation. To sum up, 17β-estradiol can modulate bone homeostasis by adjusting ARC expression. ARC stimulates mitophagy in BMSCs via MAPK/Akt pathway, identifying ARC as a promising therapeutic target for postmenopausal osteoporosis (PMOP) treatment. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that a recurrent t(6;9)(q22-23;p23-24) chromosomal translocation in salivary adenoid cystic carcinoma (ACC) results in a MYB proto-oncogene transcription factor-nuclear factor I/B (MYB-NFIB) gene fusion, which has not previously been detected in any non-ACC carcinomas of the head and neck. In the present study, data on clinical factors affecting the survival rate of patients with salivary ACC from a single institution was retrospectively analyzed, and the frequency of MYB gene rearrangement determined. A total of 97 patient cases were analyzed, and young adults presenting with ACC (<40 years old) accounted for 19.6% of all patients (n=19). A total of 70.1% (n=68) displayed neurological symptoms, including pain, paraesthesia, tongue deviation, and facial paralysis. A marked majority of the analyzed tumors (85.6%) displayed evidence of MYB rearrangement. MYB rearrangement was significantly higher in patients with late Tumor-Node-Metastasis (TNM) stage cancer compared with that in patients with early TNM stage (P=0.033), as detected by a dual color MYB break-apart fluorescence in situ hybridization probe. Kaplan-Meier analysis revealed significant differences in patient overall survival (OS) time with regard to age, gender, TNM stage, neurological symptoms, margin status and MYB rearrangement. Specifically, young age was significantly associated with a shorter OS time. In summary, the present study suggested that young patients with salivary ACC presented with a worse prognosis, in contrast to the majority of patients with salivary ACC. Moreover, MYB alterations exhibited a high positive rate in salivary ACC, and therefore, the absence of MYB rearrangements may be associated with a better prognosis. [ABSTRACT FROM AUTHOR]

Process-based terrestrial ecosystem models are increasingly being used to predict carbon (C) cycling in forest ecosystems. Given the complexity of ecosystems, these models inevitably have certain deficiencies, and thus the model parameters and simulations can be highly uncertain. Through long-term direct observation of ecosystems, numerous different types of data have accumulated, providing valuable opportunities to determine which sources of data can most effectively reduce the uncertainty of simulation results, and thereby improve simulation accuracy. In this study, based on a long-term series of observations (biometric and flux data) of a subtropical Chinese fir plantation ecosystem, we use a model–data fusion framework to evaluate the effects of different constrained data on the parameter estimation and uncertainty of related variables, and systematically evaluate the uncertainty of parameters. We found that plant C pool observational data contributed to significant reductions in the uncertainty of parameter estimates and simulation, as these data provide information on C pool size. However, none of the data effectively constrained the foliage C pool, indicating that this pool should be a target for future observational activities. The assimilation of soil organic C observations was found to be important for reducing the uncertainty or bias in soil C pools. The key findings of this study are that the assimilation of multiple time scales and types of data stream are critical for model constraint and that the most accurate simulation results are obtained when all available biometric and flux data are used as constraints. Accordingly, our results highlight the importance of using multi-source data when seeking to constrain process-based terrestrial ecosystem models. [ABSTRACT FROM AUTHOR]

Deteriorated bone quality in osteoporosis challenges the success of implants, which are in urgent need for better early osseointegration as well as antibacterial property for long-term stability. As osteoporotic bone formation tangles with angiogenic clues, the relationship between osteogenesis and angiogenesis has been a novel therapy target for osteoporosis. However, few designs of implant coatings take the compromised osteoporotic angiogenic microenvironment into consideration. Here, we investigated the angiogenic effects of bioactive strontium ions of different doses in HUVECs only and in a co-culture system with BMSCs. A proper dose of strontium ions (0.2-1 mM) could enhance the secretion of VEGFA and Ang-1 in HUVECs as well as in the co-culture system with BMSCs, exhibiting potential to create an angiogenic microenvironment in the early stage that would be beneficial to osteogenesis. Based on the dose screening, we fabricated a bioactive titanium surface doped with zinc and different doses of strontium by plasma electrolytic oxidation (PEO), for the establishment of a microenvironment favoring osseointegration for osteoporosis. The dual bioactive elements augmented titanium surfaces induced robust osteogenic differentiation, and enhanced antimicrobial properties. Augmented titanium implant surfaces exhibited improved bone formation and bone-implant contact under comprehensive assessment of an in vivo bone-implant interface. In conclusion, zinc- and strontium-augmented titanium surface benefits the osseointegration in osteoporosis via promoting osteogenic differentiation, exerting antibacterial efficacy, and stimulating early angiogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Li, Wu, Zhang, Hu, Deng, Jiang, Wen and Jiang.)

The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.

Zoledronate is one of the most potent nitrogen-containing bisphosphonates which has been demonstrated to result in osteoblast apoptosis and impact osteogenic differentiation in vitro. This effect of Zoledronate on osteoblasts may partially explain bisphosphonate‑associated osteonecrosis of the jaw, a serious complication associated with treatment with bisphosphonates. Apoptosis repressor with caspase recruitment domain (ARC) is a multifunctional inhibitor of apoptosis that is physiologically expressed predominantly in post‑mitotic cells such as cardiomyocytes, neurons and skeletal muscle cells. However, its effect on human osteoblasts remains unclear. The current study aimed to investigate the effects of ARC on human osteoblasts under the treatment of high concentrations of Zoledronate. ARC‑overexpressed human osteoblasts were established and were exposed to Zoledronate with different concentrations (0, 1 and 5 µM) in vitro. Cell numbers were detected using the MTT assay, and flow cytometry was used to identity cell apoptosis. Alkaline phosphatase staining, quantitative analysis and ectopic osteogenesis in nude mice were used to evaluate the osteogenic differentiation of ARC‑overexpressed osteoblasts. It was observed that ARC is able to reverse the inhibitory effect of Zoldronate on osteoblasts. ARC is additionally able to promote osteogenic differentiation of osteoblasts and inhibit their apoptosis. These observations suggest a critical role for ARC in the regulation of human osteoblasts under Zoledronate treatment.