Gut microbiota dysbiosis has been considered to be an important risk factor that contributes to coronary artery disease (CAD), but limited evidence exists about the involvement of gut microbiota in ...the disease. Our study aimed to characterize the dysbiosis signatures of gut microbiota in coronary artery disease. The gut microbiota represented in stool samples were collected from 70 patients with coronary artery disease and 98 healthy controls. 16S rRNA sequencing was applied, and bioinformatics methods were used to decipher taxon signatures and function alteration, as well as the microbial network and diagnostic model of gut microbiota in coronary artery disease. Gut microbiota showed decreased diversity and richness in patients with coronary artery disease. The composition of the microbial community changed; Escherichia-Shigella false discovery rate (FDR = 7.5*10
and Enterococcus (FDR = 2.08*10
) were significant enriched, while Faecalibacterium (FDR = 6.19*10
), Subdoligranulum (FDR = 1.63*10
), Roseburia (FDR = 1.95*10
), and Eubacterium rectale (FDR = 2.35*10
) were significant depleted in the CAD group. Consistent with the taxon changes, functions such as amino acid metabolism, phosphotransferase system, propanoate metabolism, lipopolysaccharide biosynthesis, and protein and tryptophan metabolism were found to be enhanced in CAD patients. The microbial network revealed that Faecalibacterium and Escherichia-Shigella were the microbiotas that dominated in the healthy control and CAD groups, respectively. The microbial diagnostic model based on random forest also showed probability in identifying those who suffered from CAD. Our study successfully identifies the dysbiosis signature, dysfunctions, and comprehensive networks of gut microbiota in CAD patients. Thus, modulation targeting the gut microbiota may be a novel strategy for CAD treatment.
Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet ...on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt
CD3
group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
Emerging research has revealed regulation of colorectal cancer metabolism by bacteria.
(
) plays a crucial role in the development of colorectal cancer, however, whether
infection modifies metabolism ...in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells
and
by regulating the epithelial-mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal
and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high
levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover,
was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that
promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for
-infected patients with colorectal cancer. SIGNIFICANCE: This study uncovers a mechanism by which
regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13-EpOME axis in
-infected patients.
Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific ...effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/Kras
mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/Kras
mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment.
...sequence analysis of RNA extracted from the cell culture supernatants on MiSeq platform (Illumina inc., San Diego, CA, USA) and ABI 3130 automatic DNA analyzer (Life Technologies, Applied ...Biosystems, Foster City, CA, USA) showed that H3, N2, H7, and N9 genes coexisted in the sample. The similarity of H3 and N2 genes of the H3N2 viruses isolated from the patient (A/Nanjing/M1/2013, GISAID accession number EPI450524 and EPI450525) and currently circulating seasonal H3N2 virus (A/Texas/JMM_21/2012H3N2) was 99·5% and 99·8%, respectively. Since mid-April, 2013 (figure, appendix), pdm2009 H1N1 has replaced H3N2 to become the dominant strain in Jiangsu Province, China.
Influenza A (H7N9) virus has been causing human infections in China since February 2013, raising serious concerns of potential pandemics. Previous studies demonstrate that human infection is directly ...linked to live animal markets, and that the internal genes of the virus are derived from H9N2 viruses circulating in the Yangtze River Delta area in Eastern China. Here following analysis of 109 viruses, we show a much higher genetic heterogeneity of the H7N9 viruses than previously reported, with a total of 27 newly designated genotypes. Phylogenetic and genealogical inferences reveal that genotypes G0 and G2.6 dominantly co-circulate within poultry, with most human isolates belonging to the genotype G0. G0 viruses are also responsible for the inter- and intra-province transmissions, leading to the genesis of novel genotypes. These observations suggest the province-specific H9N2 virus gene pools increase the genetic diversity of H7N9 via dynamic reassortments and also imply that G0 has not gained overwhelming fitness and the virus continues to undergo reassortment.
Methicillin-resistant
Staphylococcus aureus
(MRSA) causes an enormous illness burden, including skin and soft tissue infections (SSTIs), pneumonia, bloodstream infections (BSI), and sepsis. BSI are ...associated with significant patient morbidity and mortality worldwide. However, limited information is available on MRSA-related BSI in China. This study aimed to investigate the molecular characterization of 77 MRSA isolates recovered from hospitalized patients with BSI between 2012 and 2020 at three first-class tertiary hospitals in southern China based on multilocus sequence typing (MLST),
spa
typing, and staphylococcal cassette chromosome mec (SCC
mec
) typing. Overall, 13 clonal complexes (CCs) were identified, with CC59 and CC5 being the largest clusters, indicating high genetic diversity among BSI-causing MRSA isolates. ST59 was the most prevalent MLST type (22.1%). ST5/ST764-MRSA SCC
mec
II was the predominant adult MRSA clone, whereas ST59-MRSA SCC
mec
IV was the most common pediatric MRSA clone. ST5-t2460, ST764-t1084, and ST59-t437 were the most common types of adult MRSA isolates, whereas ST59-t437 and ST59-t172 were the predominant types of children’s MRSA isolates. ST59-SCC
mec
IV/V represented the most common clone among community acquired-MRSA isolates. ST5/ST764-SCC
mec
II was the most common type of hospital-associated MRSA isolate. The most prevalent toxin-encoding genes detected were
hla
,
hld
,
icaA
, and
clfA
(96.1–100%). Forty-three (100%, 43/43) isolates harbored more than 18 of the tested virulence genes in adults and eight virulence genes (23.5%, 8/34) in children. Virulence gene analysis revealed diversity among different clones: the positivity rates for the Panton-Valentine leukocidin (PVL) gene were 55.8 and 35.3% in adult and pediatric MRSA isolates, respectively; the genes
seb–sei
were present in all adult strains;
seb–seg–sei–seo
were present in all ST5, ST59, ST15, ST45, and ST22 adult strains; and
seg–sei–sem–sen–seo
were present in different clones, including ST15, ST45, and ST22 adult MRSA isolates and ST25, ST30, ST546, and ST72 children’s MRSA isolates. Adult MRSA isolates had significantly higher antibiotic resistance rates and virulence gene prevalence than pediatric MRSA isolates. For 8 years, this study provided epidemiological data on the molecular characteristics and virulence genes in different groups of MRSA BSI in China. Our findings may provide critical information for a better understanding of MRSA BSI.
Bladder cancer (BC) is a prevalent malignant tumor of the urinary system, known for its rapid progression and high likelihood of recurrence. Despite ongoing efforts, clinical diagnosis and treatment ...of BC remain limited. As such, there is an urgent need to investigate potential mechanisms underlying this disease. Exosomes, which contain a variety of bioactive molecules such as nucleic acids, proteins, and lipids, are regarded as extracellular messengers because they are implicated in facilitating intercellular communication in various diseases and are pivotal in tumor advancement, serving as a promising avenue for such researches. Nevertheless, the heterogeneous nature of BC necessitates further exploration of the potential involvement of exosomes in disease progression. This review comprehensively outlines the biological attributes of exosomes and their critical roles in tumorigenesis, while also discussing their potential applications in regulating the progression of BC involving clinical diagnosis, prognostication and treatment.
Bladder cancer poses a challenge for clinical diagnosis and treatment with the rapid progression and high recurrence rate. Exosomes play a key role in tumor progression. This review comprehensively outlines the biological characteristics of exosomes and their critical roles in tumorigenesis, while also discussing the potential applications in the clinical diagnosis and treatment of bladder cancer.
Hepatocellular carcinoma (HCC) is one of the most aggressive cancers, with limited new diagnostic and therapeutic measures. This study aimed to investigate the utility of specific serum and exosome ...lncRNAs as biomarkers for early diagnosis of HCC.
: The relative expression levels of eight selected lncRNAs in serum were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in the training and validation sets of HCC patients and matched healthy controls. Additionally, the stability, specificity and diagnostic efficiency of these lncRNAs were evaluated to determine their potential as biomarkers. The levels of the final validated lncRNAs in exosome and urine samples of 15 HCC patients and 15 healthy controls were examined for source and path analysis.
: LINC00161 was significantly upregulated in serum samples of HCC patients and showed excellent stability and specificity (
< 0.001, fold change=2.85). The area under the receiver operating characteristic (ROC) curve of the validated lncRNA signature was 0.794 (95% CI, 0.712-0.877). LINC00161 expression was detected in serum exosome, exosome-free, and urine samples, and its levels in serum exosome were upregulated in patients with HCC as compared to controls (
= 0.011, fold change=4.27).
Our results indicated that circulating exosomal LINC00161 in serum may be a novel biomarker for HCC. LINC00161 is derived from exosomes into serum and may at least be partly metabolized through urine.
Long non-coding RNAs (lncRNAs) can play significant regulatory roles in cells that affect the development and acquired drug resistance of lung cancer. Herein, we report that lncRNA linc00665 is ...significantly upregulated in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. linc00665 affects the sensitivity of NSCLC cells to the chemotherapy drug cisplatin (DDP), making it a potential target for the treatment of NSCLC. Functional experiments showed that linc00665 enhanced the proliferation and migration of NSCLC cells in vivo and in vitro, and knocking down linc00665 could enhance the drug sensitivity of NSCLC cells to DDP. Further work revealed that linc00665 could recruit enhancer of zeste homolog 2 (EZH2) to the promoter region of cyclin-dependent kinase inhibitor 1C (CDKN1C) to inhibit its transcription and thus carry out its tumorigenic role. In conclusion, our study elucidated the carcinogenic role of the linc00665-EZH2-CDKN1C axis in NSCLC tumors and its ability to influence the sensitivity of these tumors to DDP. These results suggest that linc00665 may be a potential diagnostic marker and therapeutic target in NSCLC, and they also provide a new direction for the development of clinical reversal methods for acquired drug resistance in patients with NSCLC.
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Yang et al. showed that linc00665 could recruit EZH2 enhancer into the promoter region of CDKN1C and inhibit its transcription, thus promoting the development of NSCLC cells and inhibiting their sensitivity to cisplatin. These results provide a new direction for clinical reversal of acquired drug resistance in NSCLC patients.
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