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Background: Yanghe decoction is a famous formula consisting of Rehmannia , deer horn gum, cinnamon, rue, Ephedra , ginger charcoal, and licorice. However, few studies have explored the role of the potential mechanism of Yanghe decoction in the treatment of Hashimoto's thyroiditis by metabolomics., Methods: Nine mice were randomly divided into three groups: control group (group C), model group (group M), and drug administration group (group T), with three mice in each group. Mice in groups M and T were established as models of Hashimoto's thyroiditis, and group T was treated with Yanghe decoction. The metabolome of plasma samples from each group of mice was determined using mass spectrometry coupled with high-performance liquid and gas phases, and nuclear magnetic resonance. Based on the three assays, principal component analysis was performed on all samples, as well as orthogonal partial least squares-discriminant analysis and differential metabolite molecules for groups M and T. Subsequently, pathway enrichment analysis was performed, and the intersection was taken for the differential metabolites screened in the M and T groups. The levels of inflammatory factors IL-35 and IL-6 within the serum of each group of mice were detected., Results: The difference analysis showed that a total of 38 differential metabolites were screened based on mass spectrometry coupled with the high-performance liquid phase, 120 differential metabolites were screened based on mass spectrometry coupled with gas phase, and a total of α -glucose and β -glucose were the differential metabolites analyzed based on NMR test results. The pathways enriched by the differential metabolites in the M and T groups were intersected, and a total of 5 common pathways were obtained (amino acid tRNA biosynthesis, D-glutamine and D-glutamate metabolism, tryptophan metabolism, nitrogen metabolism, and arginine and proline metabolism). The results also showed a significant decrease in the serum inflammatory factor IL-35 and a significant increase in IL-6 in mice from group M compared with group C, while a significant increase in the serum inflammatory factor IL-35 and a significant decrease in IL-6 in mice from group T compared with group M., Conclusion: Our study reveals the metabolites as well as a metabolic network that can be altered by Yanghe decoction treatment of Hashimoto's thyroiditis and shows that Yanghe decoction can effectively reduce the level of inflammatory factors in Hashimoto's thyroid., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xing Zhang et al.)

Bromodomain-containing protein 4 (BRD4) is overexpressed in thyroid carcinoma, represents as an important therapeutic target. ARV-825 is a novel cereblon-based PROTAC (Proteolysis Targeting Chsimera) compound. It can induce fast and sustained BRD4 protein degradation. Its potential effect in human thyroid carcinoma cells was studied here. In TPC-1 cells and primary human thyroid carcinoma cells, ARV-825 potently inhibited cell viability, proliferation and migration. Furthermore, ARV-825 induced robust apoptosis activation in the thyroid carcinoma cells. ARV-825 induced BRD4 protein degradation and downregulation of its targets, including c-Myc, Bcl-xL and cyclin D1 in thyroid carcinoma cells. It was significantly more potent in inhibiting thyroid carcinoma cells than the known small molecule BRD4 inhibitors. In vivo studies demonstrated that ARV-825 oral administration potently suppressed TPC-1 xenograft tumor growth in severe combined immunodeficient mice. BRD4 protein degradation as well as c-Myc, Bcl-xL and cyclin D1 downregulation were detected in ARV-825-treated TPC-1 tumor tissues. Taken together, ARV-825 induces BRD4 protein degradation and inhibits thyroid carcinoma cell growth in vitro and in vivo .

The development of novel anti-papillary thyroid carcinoma agents is urgent. AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4) inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival, proliferation and cell cycle progression in TPC-1 cells and primary human thyroid carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly attenuated with co-treatment of the caspase inhibitors. BRD4 expression was elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1 and primary cancer cells. In vivo, oral administration of AZD5153 at well-tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1, were also downregulated in AZD5153-treated tumor tissues. Collectively, the results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma cell growth in vitro and in vivo., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation. Significantly, downregulation of microRNA-25-5p (miR-25-5p), a PKCζ-targeting miRNA, could be the cause of PKCζ upregulation. Exogenous expression of miR-25-5p silenced PKCζ to activate AMPK signaling, which inhibited HT-29 cell proliferation. In vivo studies showed that HT-29 xenograft growth in mice was inhibited after expressing PKCζ shRNA or miR-25-5p. Collectively, PKCζ could be a novel oncogenic protein of human CRC. PKCζ silence, by targeted-shRNA or miR-25-5p expression, activates AMPK and inhibits HT-29 cell proliferation., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.