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Artemisia selengensis Turcz (AST) as a common vegetable is rich in di‐caffeoylquinic acids (di‐CQAs) and has been reported to possess multiple health benefits. However, whether di‐CQAs from AST leaf extracts (ASTE) could alleviate gout inflammation is still unknown. Herein, this study explored the inhibitory mechanism of ASTE on gout inflammation in THP‐1 macrophages. Results suggested that ASTE suppressed the secretion and mRNA levels of inflammatory cytokines including interleukin‐18, interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α. Pretreatment with ASTE inhibited lipopolysaccharide‐induced of IκBα degradation, p65 phosphorylation and up‐regulation of Nucleotide‐binding oligomerization domain‐like receptor containing pyrin domain 3 (NLRP3) inflammasome proteins. Moreover, ASTE inhibited monosodium urate‐induced the up‐regulation of active caspase‐1 and interleukin‐1β, promoted nuclear factor E2‐related factor2 (Nrf2) to translocate into the nucleus, reducing the generation of MSU‐induced reactive oxygen species. These results suggested that ASTE alleviated gout inflammation via inhibiting NLRP3 inflammasome activation and activating Nrf2 signaling pathway. Practical applications: Artemisia selengensis Turcz (AST) as a common vegetable in China belongs to genus Artemisia, which are rich in di‐caffeoylquinic acids. This study aimed to investigate the effect of ASTE on alleviating gout inflammation and whether NLRP3 inflammasome and Nrf2 signaling pathways are involved in the protection of ASTE against gout inflammation. Our findings are significant for developing di‐CQAs from AST by‐products as an effective functional food for preventing gout. [ABSTRACT FROM AUTHOR]

Background and aims It is commonly believed that diabetes is an important contributor to heart failure (HF) development. However, the detail effect of diabetogenesis on HF is controversy: both beneficial and harmful roles were reported. In the present study, we aim to explore the unambiguous action of diabetes on chronic HF progression and the underlying mechanism. Methods Diabetes and myocardial infarction (MI) were induced by streptozotocin (STZ) injection and left-sided thoracotomy and left anterior descending coronary artery (LAD) ligation, respectively. Pyridoxamine was used as the antagonist of advanced glycation end products (AGEs). Adult male SD rats were assigned to 5 groups: Sham; MI; Diabetes (D); Diabetes + MI (DMI) and DMI + pyridoxamine (DMI + P). Animals were sacrificed at the end of 12 weeks. The comparison of LV myocardium was made between border zone from MI or DMI animals and control LV tissues from sham-operated animals. Cardiomyocytes and dendritic cells were prepared from the Sprague–Dawley rats and cocultured in the presence or absence of AGEs. Results DMI group showed highest level of AGEs and inflammatory markers, which were significantly reduced in the presence of pyridoxamine. In vitro experiment disclosed AGEs could stimulate DCs differentiation and promote cytokines production, finally upregulated hypertrophy-related genes expression in cardiocytes. Intervention DCs differentiation was sufficient to improve cardiocytes morphology. Conclusion Our results clearly demonstrate that diabetes would promote chronic HF progression at least in part through stimulating DCs differentiation and series downstream inflammatory responses induced by AGEs. [ABSTRACT FROM AUTHOR]

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-β1 (TGF-β1) signaling has been shown to play an important role in EMT. In this study, we investigated how TGF-β1 signaling pathways contributed to EMT in three ESCC cell lines as well as 100 patients of nomadic ethnic Kazakhs residing in northwest Xinjiang Province of China. In vitro analyses included Western blotting to detect the expression of TGF-β1/Smad and EMT-associated proteins in Eca109, EC9706 and KYSE150 cell lines following stimulation with recombinant TGF-β1 and SB431542, a potent inhibitor of ALK5 that also inhibits TGF-β type II receptor. TGF-β-activated Smad2/3 signaling in EMT was significantly upregulated as indicated by mesenchymal markers of N-cadherin and Vimentin, and in the meantime, epithelial marker, E-cadherin, was markedly downregulated. In contrast, SB431542 addition downregulated the expression of N-cadherin and Vimentin, but upregulated the expression of E-cadherin. Moreover, the TGF-β1-induced EMT promoted invasion capability of Eca109 cells. Tumor cells undergoing EMT acquire fibroblastoid-like phenotype. Expressed levels of TGF-β1/Smad signaling molecules and EMT-associated proteins were examined using immunohistochemical analyses in 100 ESCC tissues of Kazakh patients and 58 matched noncancerous adjacent tissues. The results showed that ESCC tissues exhibited upregulated expression of TGF-β1/Smad. We also analyzed the relationship between the above proteins and the patients' clinicopathological characteristics. The TGF-β1/Smad signaling pathway in human Eca109 ESCC cells may carry similar features as in Kazakh ESCC patients, suggesting that TGF-β1/Smad signaling pathway may be involved in the regulation of EMT in ethnic Kazakh patients with ESCC from Xinjiang, China. [ABSTRACT FROM AUTHOR]

LRP6 is a common coreceoptor for different G protein-coupled seven-transmembrane receptors in production of cAMP. Extracelluar proteins sclerostin and DKK1, initially identified as antagonists for Wnt signaling by binding to LRP6, are negative regulators for bone formation. Here, we show that both sclerostin and DKK1 inhibit PTH-stimulated cAMP production. In addition, PTH suppresses expression of sclerostin in osteocytes in mice. We also found that sclerostin and DKK1 binds to LRP6 as antagonists to increase the availability of LRP6 to facilitate PTH signaling in a positive-feedback fashion. These studies reveal a previously unrecognized function of sclerostin and DKK1, which provides an alternative explanation for the application of sclerostin and DKK1 neutralization on enhancing bone formation as a potential therapy for skeletal diseases. [ABSTRACT FROM AUTHOR]