Gelatin, a natural polymer, provides excellent tissue compatibility for use in tissue rehabilitation. Bioactive glasses (BAG) offer superior capacity in stimulating a bioactive response but show high variability in uptake and solubility. To tackle these drawbacks, a combination of gelatin with BAG is proposed to form composites, which then offer a synergistic response. The cross-linked gelatin structure’s mechanical properties are enhanced by the incorporation of the inorganic BAG, and the rate of BAG ionic supplementation responsible for bioactivity and regenerative potential is better controlled by a protective gelatin layer. Several studies have demonstrated the cellular benefits of these composites in different forms of functional modification such as doping with zinc or incorporation of zinc such as ions directly into the BAG matrix. This review presents a comprehensive perspective on the individual characteristics of BAG and gelatin, including the synthesis and mechanism of action. Further, adaptation of the composite into various applications for bone tissue engineering is discussed and future challenges are highlighted.
Both the tumor and tumor microenvironment (TME) are crucial for pathogenesis and chemotherapy resistance in multiple myeloma (MM). Bortezomib, commonly used for MM treatment, works on both MM and TME cells, but innate and acquired resistance easily develop. By single-cell RNA sequencing (scRNA-seq), we investigated bone marrow aspirates of 18 treatment-naïve MM patients who later received bortezomib-based treatments. Twelve plasma and TME cell types and their subsets were identified. Suboptimal responders (SORs) to bortezomib exhibited higher copy number alteration burdens than optimal responders (ORs). Forty-four differentially expressed genes for SORs based on scRNA-seq data were further analyzed in an independent cohort of 90 treatment-naïve MMs, where 24 genes were validated. A combined model of three clinical variables (older age, low absolute lymphocyte count, and no autologous stem cell transplantation) and 24 genes was associated with bortezomib responsiveness and poor prognosis. In T cells, cytotoxic memory, proliferating, and dysfunctional subsets were significantly enriched in SORs. Moreover, we identified three monocyte subsets associated with bortezomib responsiveness and an MM-specific NK cell trajectory that ended with an MM-specific subset. scRNA-seq predicted the interaction of the GAS6-MERTK, ALCAM-CD6, and BAG6-NCR gene networks. Of note, tumor cells from ORs and SORs were the most prominent sources of ALCAM on effector T cells and BAG6 on NK cells, respectively. Our results indicate that the complicated compositional and molecular changes of both tumor and immune cells in the bone marrow (BM) milieu are important in the development and acquisition of resistance to bortezomib-based treatment of MM.
Background Transforming growth factor-β (TGF-β) signaling is a double-edged sword in cancer development and progression. TGF-β signaling plays a tumor suppressive role during the early stages of tumor development but promotes tumor progression in later stages. We have previously identified various mutations of TGF-β receptor II (TβRII) in human oral squamous cell carcinoma (OSCC) samples. In the present study we analyzed I227T/N236D mutation of TβRII, which was detected in the metastatic lymph node of an OSCC patient. Methods The effect of I227T/N236D TβRII mutation on transcriptional activities was measured using DR26 cells, which lack functional TβRII. HSC2 human OSCC cells stably expressing wild-type and I227T/N236D mutant TβRII were generated and used to examine the effect of I227T/N236D TβRII mutation on xenograft tumor growth, in vitro cell proliferation, apoptosis, migration, and invasion. Results The I227T/N236D mutation of TβRII upregulated TGF-β signaling and promoted xenograft tumor growth when compared with the wild-type, without affecting the in vitro proliferative capacities. To delineate the differences in proliferative capacities in vivo and in vitro, the apoptotic and survival signals were analyzed following curcumin treatment. Concomitant with apoptotic induction, epidermal growth factor receptor (EGFR) activation was observed upon curcumin treatment, which was further activated in I227T/N236D mutant transfectant cells when compared with wild-type cells. Enhanced EGFR activation correlated with cell survival and apoptotic resistance. Enhanced migratory and invasive capabilities of I227T/N236D mutant cells also depended on EGFR signaling. Conclusions These results suggest that enhanced EGFR signaling via upregulated TGF-β signaling shifted the balance toward survival and promoted cell migration and invasion in I227T/N236D mutant cells, elucidating the role of I227T/N236D mutation of TβRII in OSCC progression.
group I human carcinogen by the International Agency for Research on Cancer (IARC) (Humans, 2004). Nevertheless, the molecular mechanism by which AN induces OSF and OSCC is still unclear. Furthermore, existing treatments for OSF provide only temporary symptomatic relief and until data, no effective treatment has been established. We previously suggested a molecular mechanism that transforms OSF to oral malignancy and the
Mulberry leaves extract (Morus alba extracts; MAE) is known to have therapeutic potentials for numerous human diseases, including diabetes, neurological disorders, cardiovascular diseases, and cancers. However, there has not been sufficient research proving therapeutic effects on oral disease and its related oral risk factors. Thus, we investigated whether MAE has any anti-inflammatory and anti-bacterial effects on risk factors causing oral infectious diseases. To examine the anti-inflammatory response and bacterial inhibition of MAE, we measured intracellular reactive oxygen species (ROS) generation, production of pro-inflammatory cytokines, and the bacterial growth rate. Our study showed that MAE has anti-inflammatory activities, which inhibit the ROS generation and suppressed the production of pro-inflammatory cytokines (TNF-α and IL-6) in human monocyte THP-1 cells by stimulating lipopolysaccharide (LPS) and/or F. nucleatum, which are the virulent factors in periodontal diseases. Furthermore, MAE inhibited the bacterial growth on oral microorganisms (F. nucleatum and S. mutans) infected THP-1 cells. These findings suggested that MAE could be a potential natural source for therapeutic drugs in oral infectious disease.
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