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Thyroid cancer (TC) is one of the most prevalent endocrine malignancy with a steadily increasing incidence globally. Although standard treatments like thyroidectomy and radioiodine therapy effectively manage most cases of differentiated thyroid cancers (DTC), certain recurrent cases or those involving poorly differentiated thyroid cancers (PDTC) demand more specialized interventions. Follicular thyroid cancer (FTC) is the second most common type of DTC, and frequently metastasizes through the bloodstream to distant sites such as bones and lungs which is a leading cause of metastatic and recurrent DTC and significantly affects survival. However, existing drugs primarily address symptom management without offering a curative solution. Therefore, it is urgent to develop a new therapeutic agent for these challenging cases. Evodiamine (EVO), extracted from Evodia rutaecarpa , has shown potential as an anti-cancer agent in multiple types of human cancers including anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) cells. However, the anti-cancer effects of EVO on FTC have remained unclear. Therefore, the present study aims to investigate the anti-cancer effects of EVO in FTC cells. Our data showed that EVO effectively inhibits FTC cell growth, induces cell cycle arrest, and triggers apoptosis. Additionally, our study explored the underlying mechanisms through which EVO affects signaling pathways. To verify the anti-cancer effects of combination chemotherapy, EVO and doxorubicin were used together in FTC cells. In conclusion, this study demonstrates that EVO shows significant anti-human FTC activity, making it a promising therapeutic candidate for the treatment of follicular thyroid cancers., Competing Interests: None., (AJCR Copyright © 2024.)

Programmed death-1 (PD-1)/PD ligand-1 (PD-L1)-mediated immune escape contributes to cancer development and has been targeted as an anti-cancer strategy. Here, we show that inhibition of the RNA helicase DDX3 increased CD8 + T cell infiltration in syngeneic oral squamous cell carcinoma tumors. DDX3 knockdown compromised interferon-γ-induced PD-L1 expression and, in particular, reduced the level of cell-surface PD-L1. DDX3 promoted surface PD-L1 expression by recruiting the adaptor protein 2 (AP2) complex to the 3' UTR of PD-L1 mRNA. DDX3 depletion or 3' UTR truncation increased the binding of the coatomer protein complexes to PD-L1, leading to its intracellular accumulation. Therefore, this 3' UTR-dependent mechanism may counteract cellular negative effects on surface trafficking of PD-L1. Finally, pharmaceutic disruption of DDX3's interaction with AP2 reduced surface PD-L1 expression, supporting that the DDX3-AP2 pathway routes PD-L1 to the cell surface. Targeting DDX3 to modulate surface trafficking of immune checkpoint proteins may provide a potential strategy for cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA 1c level 8.1% [0.6%]) completed the trial. At week 20, HbA 1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA 1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes., (© 2023. The Author(s).)

Skeletal stem cells residing in the suture mesenchyme are responsible for calvarial development, homeostatic maintenance, and injury-induced repair. These naïve cells exhibit long-term self-renewal, clonal expansion, and multipotency. They possess osteogenic abilities to regenerate bones in a cell-autonomous manner and can directly replace the damaged skeleton. Therefore, the establishment of reliable isolation and culturing methods for skeletal stem cells capable of preserving their stemness promises to further explore their use in cell-based therapy. Our research team is the first to isolate and purify skeletal stem cells from the calvarial suture and demonstrate their potent ability to generate bone at a single-cell level. Here, we describe detailed protocols for suture stem cell (SuSC) isolation and stemness maintenance in culture. These methods are extremely valuable for advancing our knowledge base of skeletal stem cells in craniofacial development, congenital deformity, and tissue repair and regeneration., Competing Interests: Competing interestsThe authors declare no competing financial interests., (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)