The prevalence of vitamin D deficiency was ~80% in patients hospitalised with CAP. Vitamin D deficiency was also a significant predictor of increased 28-day all-cause mortality.
Intestinal microbiota can be changed by diet and its composition is directly related to an individual's health. In the present study, the effects of kimchi as a synbiotics on adult females' intestinal microbiota were examined.One hundred male and female study applicants were invited to apply; of those 12 females met the study criteria and were chosen as study participants. The 12 females were divided into a low kimchi intake group (15 g/day, 15% of the average Korean daily kimchi intake) and a high kimchi intake group (150 g/day) based on the amount kimchi intake, and they were provided with boarding for 7 days.To analyze the intestinal microorganisms, feces samples from 12 female participants were obtained. The 16S ribosomal RNA genes of the microorganisms in those samples were examined using customized microarray chips to identity 702 species of intestinal microorganisms in 17 phyla. In the high kimchi group, the percentage of 16 species of microorganisms, including Gammaproteobacteria containing many pathogenic microorganisms decreased to less than half the percentage and the percentage of 18 species microorganisms, including 6 species of kimchi-dominant fermenting microorganisms, such as Leuconostoc mesenteroides, increased to at least twice. Changes in the intestinal microbiota based on kimchi intake were examined hourly for 7 days using quantitative real-time PCR. Among the 12 species of kimchi-dominant microorganisms, 3 species of lactic acid bacteria, including Leuconostoc mesenteroides, increased in the high intake group.These study results indicate that kimchi intake affected the formation of intestinal microbiota. Although personal differences were observed in the individual participants, kimchi was shown to affect the formation of intestinal microbiota and to be beneficial as a healthy synbiotics.
Currently, there are no effective therapies for patients with triple-negative breast cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC. Herein, we undertook a comprehensive study to evaluate the activity of a first-in-class Mnk1/2 protein degraders, in clinically relevant models of TNBC. These studies enabled us to identify racemic VNLG-152R as the most efficacious Mnk1/2 degrader. By targeting Mnk1/2 protein degradation (activity), VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulated downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited remarkable antitumor and antimetastatic activities against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel therapeutic strategy that can be developed as monotherapy for effective treatment of patients with primary/metastatic TNBC.
Keywords:Breast cancer / metastasis / Mnk1/2 degraders / Mnk/eIF4E/mTORC1 / TNBC.
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