Diadenosine tetraphosphate modulated quorum sensing in bacteria treated with kanamycin.

BACKGROUND: The dinucleotide alarmone diadenosine tetraphosphate (Ap4A), which is found in cells, has been shown to affect the survival of bacteria under stress. RESULTS: Here, we labeled Ap4A with biotin and incubated the labeled Ap4A with the total proteins extracted from kanamycin-treated Escherichia coli to identify the Ap4A binding protein in bacteria treated with kanamycin. Liquid chromatography‒mass spectrometry (LCMS) and bioinformatics were used to identify novel proteins that Ap4A interacts with that are involved in biofilm formation, quorum sensing, and lipopolysaccharide biosynthesis pathways. Then, we used the apaH knockout strain of E. coli K12-MG1655, which had increased intracellular Ap4A, to demonstrate that Ap4A affected the expression of genes in these three pathways. We also found that the swarming motility of the apaH mutant strain was reduced compared with that of the wild-type strain, and under kanamycin treatment, the biofilm formation of the mutant strain decreased. CONCLUSIONS: These results showed that Ap4A can reduce the survival rate of bacteria treated with kanamycin by regulating quorum sensing (QS). These effects can expand the application of kanamycin combinations in the treatment of multidrug-resistant bacteria.

Construction of model animals to explore intestinal microbiome for detection of breast cancer.

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.

The Associations of Cerebrospinal Fluid Ferritin with Neurodegeneration and Neuroinflammation Along the Alzheimer's Disease Continuum.

BACKGROUND: Increasing evidence has suggested that iron accumulation plays an important role in the onset and development of Alzheimer's disease (AD). However, the potential mechanism remains unclear. OBJECTIVE: The present study investigated the associations of cerebrospinal fluid (CSF) ferritin, an indicator for brain iron load, with neurodegenerative and inflammatory changes in AD. METHODS: The study involved 302 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). They were classified as normal controls (A-T-N-, n = 48), AD continuum (A+TN-, n = 46; A+TN+, n = 166), and suspected non-AD pathology (A-TN+, n = 42), according to the amyloid/tau/neurodegeneration (ATN) system. Group comparisons of CSF ferritin among groups were performed using one-way ANOVA. Linear regression models were used to test the relationships between CSF ferritin and cognitive assessments, and the associations between CSF ferritin and other biomarkers, respectively. RESULTS: We found that CSF ferritin showed significant differences among the ATN groups, with higher concentration in more advanced categories (A+TN+). Furthermore, CSF ferritin level was independently related to cognitive performance (MMSE, ADAS-Cog13, and ADNI-mem). Linear regression analysis indicated positive relationships between CSF ferritin and phosphorylated tau and total tau, rather than Aß42. Significant associations were revealed between CSF ferritin and inflammatory proteins, including TNF-α, TNFR1, TNFR2, ICAM1, VCAM1, TGF-ß1, IL-9, and IP-10, respectively. CONCLUSION: Our results provide new insight into iron dysfunction in AD pathology and highlight elevated brain iron as a possible mechanism of neurodegeneration and neuroinflammation along AD continuum.