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Breast cancer ranks first among female cancers and has become a major public health problem in the current society. More studies indicated that these cancers are related to the change in the gut microbiome that can cause metabolic and immune system disorders in the body. However, there are few studies on the changes in gut microbiome caused by the onset of breast cancer, and the relationship between breast cancer and gut microbiome needs to be further clarified. In this study, we inoculated 4T1 breast cancer cells to induce breast cancer tumorigenesis in mice and collected their feces samples at different stages during this process. These intestinal florae were analyzed using 16S rRNA gene amplicon sequencing, and the results showed that at the phylum level, the ratio of Firmicutes/Bacteroidetes decreased with the development of the tumor; at the family level, the intestinal microbiome had obvious variations of Lachnospiraceae, Bacteroidaceae, Erysipelotrichaceae, etc. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated that decreased abundance of cancer-related signaling pathways. This study elucidated the relationship between breast cancer and intestinal microbiome, and the research results can be used as an important biomarker for the diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Studies relating obesity to cognition in older people show conflicting results, which may be explained by the choice of obesity indicators. Objectives: This study aimed to investigate the relationship between obesity-related indicators and cognitive impairment, especially between different age or gender subgroups, and explore whether obesity-related indicators were related to specific cognitive domains. Methods: This was a cross-sectional study on 1753 participants aged ≥ 60 years (41.0% men; aged 71.36 ± 5.96 years). Obesity-related indicators included body mass index (BMI), waist circumference (WC), calf circumference (CC), waist to hip ratio (WHR), waist to calf circumstance ratio (WCR), fat to fat-free mass ratio (FM/FFM). The Mini-Mental State Examination scale (MMSE) was used to assess cognitive function. Cognitive impairment was defined as a score ≤ 17 for illiterates, ≤ 20 for participants with primary school education, and ≤ 24 for those with junior high school degrees or above. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to analyze and visualize the linear relationships. Results: The prevalence of cognitive impairment was 18.77%. In the fully adjusted model, CC was negatively associated with cognitive impairment (OR = 0.94, 95% CI: 0.90−0.98). Further analysis showed that CC correlated positively with recall and place orientation. A higher FM/FFM was found to be associated with a higher prevalence of cognitive impairment (OR: 1.44, 95%CI: 0.88–2.35, P for trend = 0.029); this association was notable in women (P for trend = 0.002) and the oldest (P for trend = 0.009), and so did the potential effect of BMI on cognitive impairment (70–80 years: P for trend = 0.011; ≥ 80 years: P for trend = 0.013). No statistically significant association was found between cognitive impairment and WC, WHR, or WCR. Conclusion: CC and FM/FFM were associated with cognitive impairment in older people. Future research needs to distinguish the effects of fat and muscle mass on cognitive function, with special attention to different ages and genders. [ABSTRACT FROM AUTHOR]

PKCα (protein kinase C alpha, PRKCA) is an important protein involved in several steps of signaling pathways in lung cancer, and microRNAs (miRNAs) have also been shown to participate in lung carcinogenesis. However, it is not clear how PKCα and miRNAs are correlated in the disease. In this report, we aimed to identify novel miRNAs that target PKCα and to study their biological function. Using bioinformatics analysis, we predicted one novel candidate, miR-203, and found differential expression patterns of miR-203 and PKCα in human lung cancer tissues. Moreover, we experimentally validated miR-203 as a direct regulator of PKCα. Finally, we demonstrated that the targeting of PKCα by miR-203 played a critical role in regulating cell proliferation, apoptosis and migration in lung cancer cells. In summary, this study identifies a novel miRNA that targets PKCα and illustrates that the downregulation of PKCα by miR-203 modulates biological processes in lung cancer cells. [ABSTRACT FROM AUTHOR]

Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system. [ABSTRACT FROM AUTHOR]