Imbalances in intestinal bacteria correlate with colitis-associated colorectal cancer (CAC). Traditional Chinese medicines have been used to adjust the gut microbiota, and isoliquiritigenin (ISL), a flavonoid extracted from licorice, has shown antitumor efficacy. In this study, the effects of ISL on CAC development and the gut microbiota were evaluated using an azoxymethane and dextran sulphate sodium (AOM/DSS)-induced mouse model of CAC (CACM). Histopathological analysis suggested that ISL reduced tumor incidence in vivo. Moreover, high-throughput sequencing and terminal restriction fragment length polymorphism (T-RFLP) studies of the bacterial 16S rRNA gene revealed that the structure of the gut microbial community shifted significantly following AOM/DSS treatment, and that effect was alleviated by treatment with high-dose ISL (150 mg/kg). Compared to the microbiota in the control mice (CK), the levels of Bacteroidetes decreased and the levels of Firmicutes increased during CAC development. ISL reversed the imbalance at the phylum level and altered the familial constituents of the gut microbiota. Specifically, the abundance of Helicobacteraceae increased after treatment with high-dose ISL, while the abundance of Lachnospiraceae and Rikenellaceae decreased. At the genus level, ISL reduced the abundance of opportunistic pathogens (Escherichia and Enterococcus), and increased the levels of probiotics, particularly butyrate-producing bacteria (Butyricicoccus, Clostridium, and Ruminococcus). Thus, ISL protects mice from AOM/DSS-induced CAC, and ISL and the gut microbiota may have synergistic anti-cancer effects.

Purpose The main objectives of the present study were to detect the antimicrobial susceptibility and molecular characteristics of Klebsiella pneumoniae isolated from different hosts and to investigate the possibility of K. pneumoniae transmission between animals and humans. Materials and methods A total of 189 nonduplicate K. pneumoniae isolates were collected from hospitals and four species of animals in Henan Province, China. The disk diffusion method was used for antimicrobial susceptibility testing, and resistance and virulence genes were screened by polymerase chain reaction (PCR). The molecular types were identified through multilocus sequence typing (MLST), and the hypermucoviscous (HMV) phenotype was identified using the “string-forming test”. Pearson’s parameters were used to determine the potential link among the molecular types and resistance and virulence genes of all K. pneumoniae strains. Results The resistance rates of the 189 K. pneumoniae isolates against 15 antibiotics ranged from 11.6% to 77.8%. The highest multidrug resistance rate was detected in the pig strains (93.6%), followed by the human strains (90.4%), chicken strains (88.9%), cow strains (52.0%) and sheep strains (50.0%). Forty-eight (25.4%) K. pneumoniae strains presented the HMV phenotype. entB, fimH-1 and mrkD were the most prevalent of the detected virulence genes, and magA and rmpA were the least prevalent genes in all the isolates. The MLST analysis revealed 24 unique sequence types (STs) among from the 189 isolates. ST11, ST235 and ST258 were common STs among the five isolates of host origin. ST258 exhibited significantly positive correlations with blaNDM, magA and the HMV phenotype and a negative correlation with qnrB . Conclusion K. pneumoniae strains from different hosts, including humans and animals, have common molecular types and similar phenotypes, and these strains can potentially be transmitted between humans and animals.

Sterol regulatory element binding protein-1c (SREBP-1c), which serves an essential role in the process of fat synthesis, is a key adjustment factor that regulates the dynamic balance of lipid metabolism. SREBP-1c activates the transcription of multiple genes encoding for enzymes involved in the synthesis of triglycerides (TG) and fatty acids (FA) and accelerates lipid synthesis. Previous analysis indicated that long non-coding RNA HCV regulated 1 (lncHR1) participates in lipid metabolism in vivo and regulates the level of SREBP-1c protein. However, the mechanism of lncHR1 in regulating SREBP-1c levels has not been revealed. In the present study, a fatty degeneration cell model was used to study how lncHR1 regulates the SREBP-1c protein at the cellular level. Furthermore TG accumulation was assessed according to morphological analysis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detected the expression of SREBP-1c. An activator and an inhibitor of phosphoinositide 3-kinase/AKT phosphorylation (IGF-1 and LY294002, respectively) were used to study the effect of lncHR1 on this pathway. It was verified that lncHR1 regulated SREBP-1c levels and the phosphorylation of AKT in the steatosis cell model. Detailed molecular mechanisms mediated by lncHR1 were associated with the phosphorylation AKT/FoxO1 in Huh7 cell lines. Simultaneously, lncHR1 affected the location of FoxO1 inside and outside of the nucleus. Furthermore, the phosphorylation of PDK1 upstream of AKT was regulated through overexpression or knockdown lncHR1, as determined by western blotting. Taken together, these data show that lncHR1 inhibits SREBP-1c levels through the phosphorylation of the PDK1/AKT/FoxO1 axis.

Epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) both overexpressed on non-small cell lung cancer (NSCLC) and are known cooperatively to promote tumor progression and drug resistance. This study was to construct a novel bispecific fusion protein EGF-IGF-LDP-AE consisting of EGFR and IGF-IR specific ligands (EGF and IGF-1) and lidamycin, an enediyne antibiotic with potent antitumor activity, and investigate its antitumor efficacy against NSCLC. Binding and internalization assays showed that EGF-IGF-LDP protein could bind to NSCLC cells with high affinity and then internalized into cells with higher efficiency than that of monospecific proteins. In vitro, the enediyne-energized analogue of bispecific fusion protein (EGF-IGF-LDP-AE) displayed extremely potent cytotoxicity to NSCLC cell lines with IC50<10−11 mol/L. Moreover, the bispecific protein EGF-IGF-LDP-AE was more cytotoxic than monospecific proteins (EGF-LDP-AE and LDP-IGF-AE) and lidamycin. In vivo, EGF-IGF-LDP-AE markedly inhibited the growth of A549 xenografts, and the efficacy was more potent than that of lidamycin and monospecific counterparts. EGF-IGF-LDP-AE caused significant cell cycle arrest and it also induced cell apoptosis in a dosage-dependent manner. Pretreatment with EGF-IGF-LDP-AE inhibited EGF-, IGF-stimulated EGFR and IGF-1R phosphorylation, and blocked two main downstream signaling molecules AKT and ERK activation. These data suggested that EGF-LDP-IGF-AE protein would be a promising targeted agent for NSCLC patients with EGFR and/or IGF-1R overexpression.

S. haemolyticus is an emerging opportunistic pathogen with a high burden of antimicrobial resistance. We performed molecular epidemiological analysis of S. haemolyticus that was isolated from a hospital, and found that the phylogenetic lineages are diverse accompanied by a dominant epidemic clonal lineage ST42.