Association between added sugars and frailty in U.S. adults: a cross-sectional study from the National Health and Nutrition Examination Survey 2007-2018.

Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study. Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status. Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty. Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations.

TCOF1 coordinates oncogenic activation and rRNA production and promotes tumorigenesis in HCC.

Treacle ribosome biogenesis factor 1 (TCOF1) is a nucleolar factor that regulates ribosomal DNA (rDNA) transcription in the nucleolus. TCOF1 has been previously reported to be implicated in Treacher Collins-Franceschetti syndrome (TCS), a congenital disorder of craniofacial development. Except TCS, TCOF1 has not been reported to be involved in other diseases so far. Here, we show that TCOF1 expression is aberrantly elevated in human hepatocellular carcinoma (HCC) and correlates with HCC progression and poor outcome. In vitro and in vivo studies reveal oncogenic roles of TCOF1 in HCC. Mechanistically, TCOF1 regulates KRAS-activated genes and epithelial-mesenchymal transition (EMT) genes in HCC and is required for the increased ribosomal RNA (rRNA) production, a hallmark of cancer. Interestingly, our analysis reveals an inverse correlation between TCOF1 expression and tumor infiltration of antitumor immune cells, suggesting that TCOF1 may also have an important impact on antitumor immune responses in HCC. Together, our findings support a model in which TCOF1 coordinates oncogenic activation and rRNA production to promote HCC tumorigenesis. The inverse correlation between TCOF1 expression and the infiltration of antitumor immune cells opens a new avenue to understanding the promoting role of TCOF in HCC tumorigenesis.

C/EBPß regulates the JAK/STAT signaling pathway in triple-negative breast cancer.

C/EBPß is a member of the CCAAT/enhancer-binding protein (C/EBP) family, which consists of a number of b-ZIP transcription factors. Although C/EBPß has been implicated in the development of certain cancers, including breast cancer, it remains unknown whether dysregulation of C/EBPß in breast cancer is subtype-specific. Moreover, the underlying mechanisms by which C/EBPß regulates breast cancer carcinogenesis are not fully understood. Here, we present evidence that C/EBPß is specifically overexpressed in human TNBC samples, but not in non-TNBC samples. C/EBPß depletion dramatically suppressed TNBC cell growth, migration, invasion, and colony formation ability. A subsequent mechanistic study revealed that the JAK/STAT signaling pathway was upregulated in C/EBPß_high TNBC samples compared with C/EBPß_low TNBC samples. C/EBPß ChIP-seq and qPCR were performed to demonstrate that C/EBPß directly binds to and regulates JAK/STAT signaling pathway genes in TNBC. Taken together, our data indicate the oncogenic role of C/EBPß in human TNBC and reveal a novel mechanism by which C/EBPß promotes TNBC carcinogenesis.

CHD4/NuRD complex regulates complement gene expression and correlates with CD8 T cell infiltration in human hepatocellular carcinoma.

BACKGROUNDS: The NuRD (Nucleosome Remodeling and Deacetylation) complex is a repressive complex in gene transcription by modulating chromatin accessibility of target genes to transcription factors and RNA polymerase II. Although individual subunits of the complex have been implicated in many other cancer types, the complex's role in human hepatocellular carcinoma (HCC) is not fully understood. More importantly, the NuRD complex has not yet been investigated as a whole in cancers. METHODS: We analyzed the expression of the NuRD complex in HCC and evaluated the prognostic value of NuRD complex expression in HCC using the RNA-seq data obtained from the TCGA project. We examined the effect of CHD4 knockdown on HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition, colony-forming ability, and on complement gene expression. We also performed bioinformatic analyses to investigate the correlation between the NuRD complex expression and immune infiltration. RESULTS: We found that nine subunits, out of 14 subunits of the NuRD complex examined, were significantly overexpressed in HCC, and their expression levels were positively correlated with cancer progression. More importantly, our data also demonstrated that these subunits tended to be overexpressed as a whole in HCC. Subsequent studies demonstrated that knockdown of CHD4 in HCC cells inhibits cell proliferation, migration, invasion, and colony-forming ability and promotes apoptosis of HCC cells, indicating that the CHD4/NuRD complex plays oncogenic roles in HCC. Further analysis revealed that the CHD4/NuRD complex regulates complement gene expression in HCC. Intriguingly, we found that the CHD4/NuRD complex expression was inversely correlated with CD8 T cell infiltration in HCC. CONCLUSIONS: Our data demonstrate that the CHD4/NuRD complex plays an oncogenic role in human HCC and regulates complement gene expression in HCC cells. The results of inverse correlation between the CHD4/NuRD complex and CD8 T cell and DC cell infiltration in HCC suggest that the CHD4/NuRD complex not only plays direct regulatory roles in HCC cells, but also has an impact on the immune microenvironment of HCC.