No abstract

Background Breast cancer anti-estrogen resistance 4 (BCAR4) is closely associated with colorectal cancer (CRC) initiation and propagation. However, the mechanisms underlying BCAR4 function in colon cancer remains largely unknown. In this study, we hypothesized that BCAR4 could regulate colon cancer stem/initiating cells (CSC) function and further facilitates the colon cancer progression. Methods qRT-PCR was used to examine the expression of BCAR4 and various CSC markers. FACS, acetaldehyde dehydrogenase (ALDH) activity and western blot assays were applicable to test the expression of CSC markers. CCK8, tumorsphere formation and transwell assays were adopted to examine the capacity of CRC cells proliferation, self-renewal and migration. Pull down assay was used to test the interaction between BCAR4 and miR-665. Luciferase reporter assay was used to examine the interaction of miR-665 and activators of transcription (STAT3). In vivo tumor xenograft study was used to verify the malignancy of CRC cells with inhibition of BCAR4. Results Breast cancer anti-estrogen resistance 4 was highly expressed in both CRC cells and stem/initiating cells. In addition, overexpression of BCAR4 facilitated the maintenance of ALDH positive cells (a type of cancer stem/initiating cells) stemness and promoted ALDH+ cells proliferation and migration. Inhibition of BCAR4 restricted ALDH+ cells proliferation and migration. We further proved that miR-665 was the target of BCAR4 and subsequently activated signal transducers and STAT3 signaling which is an important pathway in cancer stem cells self-renewal. Conclusions Breast cancer anti-estrogen resistance 4 promotes the CRC cells stemness through targeting to miR-665/STAT3 signaling and identification of the BCAR4 in CRC stem cells provides a new insight into CRC diagnosis, treatment, prognosis and next-step translational investigations.

BCAR4 (Breast Cancer Anti-Estrogen Resistance 4) is a long noncoding RNA that was identified as an oncogene in breast cancer. In our research, we found that the expression level of BCAR4 was upregulated in colon cancer tissues compared to paired normal tissues. What's more, higher BCAR4 expression was correlated with lower survival rate in patients with colon cancer. Mechanistically, we showed that BCAR4 activated Wnt/β-catenin signaling in colon cancer by protecting β-catenin from degradation. We also showed that BCAR4 overexpression promoted cell proliferation and migration in colon cancer. However, silencing BCAR4 inhibited cell growth and promoted apoptosis. Besides, BCAR4 knockdown decreased tumor growth in vivo. These findings indicate that BCAR4 facilitated colon cancer progression by enhancing cell proliferation and inhibiting apoptosis via BCAR4/β-catenin axis. BCAR4 may be a useful new target for treatment of patients with colon cancer.

Salmonella is an important cause of foodborne diseases. This study was undertaken to investigate the prevalence, serotype distribution, antimicrobial resistance, virulence genes, and genetic diversity of Salmonella isolates recovered from fresh duck meat obtained from retail markets in Southern China. In total, 365 samples of fresh duck meat were collected from retail markets in six different cities of Guangdong Province between May 2017 and April 2019. High levels of Salmonella contamination were detected in duck meat (151/365, 41.4%). Twenty-six different Salmonella serotypes were identified: S. Corvallis (n = 25, 16.6%), S. Kentucky (n = 22, 14.6%) and S. Agona (n = 20, 13.3%) were the most prevalent serotypes. All isolates were resistant to at least one antibiotic and 133 (88.1%) isolates exhibited multidrug resistance (MDR). Most (86.1%) Salmonella isolates carried seven classes of virulence-associated genes. This study showed the diversity of Salmonella serotypes and genotypes and the high prevalence of MDR isolates carrying multiple virulence-associated genes among isolates from duck meat obtained from retail markets in Southern China. Isolates from different districts had similar pulsed-field gel electrophoresis (PFGE) patterns indicating that circulating foodborne Salmonella constitutes a potential public health issue across different districts.

Salmonella enterica serovar Kentucky (S. Kentucky) sequence type 198 has emerged as a global zoonotic pathogen. We explored Salmonella enterica serovar Kentucky ST198 samples from the broiler chicken supply chain and patients between 2010 and 2016. Here, we collected 180 S. Kentucky isolates from clinical cases and the poultry supply chain. We performed XbaI pulsed-field gel electrophoresis and multilocus sequence typing. We assessed mutations in the quinolone resistance-determining regions and screened for the presence of the Salmonella genomic island 1 (SGI1). We determined that 63 (35.0%) of the 180 isolates were S. Kentucky ST198. Chinese strains of S. Kentucky ST198 have a high transmission of ciprofloxacin resistance (38/63, 60.3%) and a high risk of multidrug resistance. The quinolone resistance of the S. Kentucky ST198 strain found in China may be due to mutations in its quinolone resistance-determining region. Our study firstly revealed that ciprofloxacin-resistant S. Kentucky ST198 strains can undergo cross-host transmission, thereby causing a serious foodborne public health problem in China.

In this study, we investigated the pattern of antimicrobial resistance in Salmonella enterica serotype Enteritidis isolates in Shanghai, China from 2005 to 2014. We found the first isolates with resistance to the fourth-generation cephalosporin cefepime starting in 2010. Furthermore, we analyzed the epidemic characteristics and mechanisms of underlying cefepime resistance in S. Enteritidis isolates found from 2010. In total, 38 of 2,914 (1.30%) isolates were identified as cefepime-resistant S. Enteritidis (CRSE) isolates by Kirby-Bauer disk diffusion. Two isolates were from animal derived food sources; 36 isolates were from fecal samples of human patients with salmonellosis. Antimicrobial susceptibility testing using the agar dilution method revealed that all CRSE isolates showed additional resistances at least to ceftazidime, cefotaxime, and ampicillin. Additionally, pulsed-field gel electrophoresis (PFGE) profiles indicated that 89.47% of CRSE isolates also displayed similar PFGE patterns. Five types of βlactamase genes, bla CTX-M (100.00%, 38/38), bla SHV (65.79%, 25/38), bla TEM (52.63%, 20/38), bla ACC (18.42%, 7/38), and bla PSE (5.26%, 2/38) were detected by PCR and sequencing. Among bla CTX-M genes, bla CTX-M-55 was the dominant type (84.21%, 32/38). Conjugation and transformation experiments along with plasmid replicon typing revealed that bla CTX-M-55 was located on plasmids of various replicon types with sizes ranging from 76.8 to 138.9 kb. Plasmid sequence analysis also showed that the bla CTX-M-55 gene was mobilized mainly by the ISEcp1-bla CTX-M-55-ORF477 transposition unit and had its own ISEcp1-based promoter, which accelerated the expression and transmission of bla CTX-M-55. Analysis of whole genome sequences (Illumina) of one selected transformant SH12G706-C showed high similarity of the bla CTX-M-55 carrying plasmid with the IncI1 plasmid backbone p628-CTX-M of Klebsiella pneumoniae detected in 2010 in China. The present study demonstrated that the bla CTX-M-55 gene mobilized by ISEcp1bla CTX-M-55-ORF477 was the main feature shared by CRSE isolates and seems to play an important role for transmission

No abstract

No abstract