Systematic pharmacology-based strategy to explore the mechanism of Semen Strychni for treatment of papillary thyroid carcinoma

Mao, Jingxin; Tang, Lijing; Fang, Ling; Tian, Cheng; Zhu, Zhaojing; Li, Yan

doi:10.1038/s41598-023-45741-9

Cited by 5 publications

(2 citation statements)

References 59 publications

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“…The MAPK signaling pathway is one of the common signaling pathways involved in the progression of PTC. Studies have shown that certain exogenous substances may exert anticancer effects through the MAPK signaling pathway ( 31 ). In this study, we found that autophagy may be another important mechanism in the progression of PTC.…”

Section: Discussionmentioning

confidence: 99%

The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer

Li,

Zhang,

Dionigi

et al. 2023

Front. Endocrinol.

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BackgroundSubclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity of real-world studies examining the relationship between subclinical hypothyroidism and known correlates of invasiveness of papillary thyroid carcinoma (PTC).Materials and methodsA retrospective cohort study of 13,717 patients with PTC was conducted. Odds ratios were calculated to assess the relationship between subclinical hypothyroidism and extrathyroidal extension (ETE) after adjusting for BMI and genders. The Cancer Genome Atlas (TCGA) data were utilized for the analysis of TSHR-associated pathways, while qRT-PCR was employed to validate the expression levels of pivotal genes in the relevant signaling pathways.ResultsIn total, 13,717 PTC patients (10,769 women and 2,948 men; mean [SD] age, 42.90 [9.43] years) were included in the retrospective study. Subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.168 [95% CI, 1.028–1.327]; P=0.017). In normal-weight patients, subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.287 [95% CI, 1.089–1.520]; P=0.003). However, this risk was not observed in under-weight, overweight, and obese patients. Compared to females, subclinical hypothyroidism was a higher risk factor for ETE in male patients with normal body weight (OR male=2.363 vs. OR female=1.228). Subclinical hypothyroidism was found to be a significant risk factor for ETE in the subgroup of patients younger than 38 years old (OR1 adjusted, 1.382 [95% CI, 1.032–1.852], P=0.030). The findings from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the involvement of the autophagy signaling pathway in TSHR/ETE/EMT regulation. Moreover, the gene expression levels demonstrated a concentration-dependent relationship between TSH intervention levels and the expression of key genes in the autophagy pathway of thyroid cancer cells.ConclusionSubclinical hypothyroidism was an independent risk factor for ETE in patients with PTC. This association was particularly significant in normal-weight and younger patients. The risk of ETE associated with subclinical hypothyroidism was higher in males compared to females. Our study indicates a potential involvement of the autophagy pathway in regulating the ETE phenotype in thyroid cancer, specifically in the context of subclinical hypothyroidism.

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Section: Discussionmentioning

confidence: 99%

The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer

Li,

Zhang,

Dionigi

et al. 2023

Front. Endocrinol.

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“…The results pointed out no cytochrome inhibition events or PAINS ability. Finally, additional in silico evaluations of the most promising compounds 1a-3a have been performed via SwissTarget [71,[81][82][83][84], suggesting a prominent role as GPCRs or enzyme-targeting compounds for the three aforementioned pyrimidinone-benzimidazoles 1a-3a (see Figure S4). This information is in agreement with the results herein reported regarding their TAAR1 agonism ability and also for the previously described mechanism of action as human platelet aggregation inhibitors via phosphodiesterase inhibition [59].…”

Section: Biological Evaluation Of Compounds 1a-10a As Novel Taar1 Ago...mentioning

confidence: 99%

Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling

Grossi,

Scarano,

Musumeci

et al. 2024

Molecules

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The search for novel effective TAAR1 ligands continues to draw great attention due to the wide range of pharmacological applications related to TAAR1 targeting. Herein, molecular docking studies of known TAAR1 ligands, characterized by an oxazoline core, have been performed in order to identify novel promising chemo-types for the discovery of more active TAAR1 agonists. In particular, the oxazoline-based compound S18616 has been taken as a reference compound for the computational study, leading to the development of quite flat and conformationally locked ligands. The choice of a “Y-shape” conformation was suggested for the design of TAAR1 ligands, interacting with the protein cavity delimited by ASP103 and aromatic residues such as PHE186, PHE195, PHE268, and PHE267. The obtained results allowed us to preliminary in silico screen an in-house series of pyrimidinone-benzimidazoles (1a–10a) as a novel scaffold to target TAAR1. Combined ligand-based (LBCM) and structure based (SBCM) computational methods suggested the biological evaluation of compounds 1a–10a, leading to the identification of derivatives 1a–3a (hTAAR1 EC50 = 526.3–657.4 nM) as promising novel TAAR1 agonists.

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Papillary Thyroid Carcinoma: Correlation Between Molecular and Clinical Features

Wang,

Yu,

Zhang

et al. 2024

Mol Diagn Ther

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Background Thyroid cancer is prevalent worldwide, including in China, where its incidence is on the rise. Papillary thyroid carcinoma (PTC) is the predominant subtype. Investigating the relationship between clinical data associated with PTC and gene mutations is crucial for improving detection and treatment. Patients and Methods We collected samples and associated clinical data from 700 PTC patients at Shanxi Provincial People’s Hospital. Using a panel of 57 genes linked to thyroid cancer, we sequenced the samples to determine the mutation frequency of thyroid cancer-associated genes in PTC. We further analyzed the correlation between gene variants and clinical information. Results The mean age of patients in this study was 42.5 years. Females predominated, comprising 507 of the total patient population, resulting in a female-to-male ratio of 2.63 (507:193). Tumor distribution revealed 198, 257, and 142 cases on the left, right, and both sides, respectively. Among the 57 thyroid cancer-related genes analyzed, we identified at least one driver gene in 83.6% of patients. Notably, 76.4% had BRAF mutations, mainly BRAF V600E , which constituted 90.9% of all BRAF mutations, with 535 cases exhibiting these mutations. Other significant driver genes included CHEK2 ( n = 84), RET ( n = 42), PIK3CA ( n = 7), and EGFR ( n = 7). RET fusions ( n = 28) were also identified. Notably, patients under 55 years old exhibit a higher tendency towards advanced N staging, suggesting that younger individuals may be more prone to lymph node metastasis. Additionally, male patients were more likely to have advanced N stages. Importantly, a positive correlation was observed between higher BRAF allele frequencies and more advanced T and N stages. Similarly, correlation analysis revealed that a greater frequency of RET fusions correlated with later T and N stages. Conclusion This study uncovered several significant insights. Younger PTC patients exhibited a higher propensity for lymph node metastasis. An elevated mutation frequency of BRAF was correlated with a higher occurrence of RET fusions, predisposing individuals to lymph node metastasis and potentially indicating a poorer prognosis. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-024-00721-1.

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Systematic pharmacology-based strategy to explore the mechanism of Semen Strychni for treatment of papillary thyroid carcinoma

Cited by 5 publications

References 59 publications

The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer

The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer

Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling

Papillary Thyroid Carcinoma: Correlation Between Molecular and Clinical Features

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