The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human ...microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.
Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human ...intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation.
The future of safe cell-based therapy rests on overcoming teratoma/tumor formation, in particular when using human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human ...induced pluripotent stem cells (hiPSCs). Because the presence of a few remaining undifferentiated hPSCs can cause undesirable teratomas after transplantation, complete removal of these cells with no/minimal damage to differentiated cells is a prerequisite for clinical application of hPSC-based therapy. Having identified a unique hESC signature of pro- and antiapoptotic gene expression profile, we hypothesized that targeting hPSC-specific antiapoptotic factor(s) (i.e., survivin or Bcl10) represents an efficient strategy to selectively eliminate pluripotent cells with teratoma potential. Here we report the successful identification of small molecules that can effectively inhibit these antiapoptotic factors, leading to selective and efficient removal of pluripotent stem cells through apoptotic cell death. In particular, a single treatment of hESC-derived mixed population with chemical inhibitors of survivin (e.g., quercetin or YM155) induced selective and complete cell death of undifferentiated hPSCs. In contrast, differentiated cell types (e.g., dopamine neurons and smooth-muscle cells) derived from hPSCs survived well and maintained their functionality. We found that quercetin-induced selective cell death is caused by mitochondrial accumulation of p53 and is sufficient to prevent teratoma formation after transplantation of hESC- or hiPSC-derived cells. Taken together, these results provide the “proof of concept” that small-molecule targeting of hPSC-specific antiapoptotic pathway(s) is a viable strategy to prevent tumor formation by selectively eliminating remaining undifferentiated pluripotent cells for safe hPSC-based therapy.
A total of 116 Escherichia coli isolates from cecal contents of 81 indigenous wild birds in Korea were tested for antimicrobial susceptibility. Seventy-one isolates from sparrows (Passer montanus) ...and one isolate from doves (Columba livia) were resistant to three antimicrobials, including streptomycin, sulfonamide, and tetracycline (SSuT). PCR and subsequent sequence analysis revealed the SSuT gene cluster region (approximately 13 kb) harboring genes encoding resistance to streptomycin (strA and strB), sulfonamide (sul2), and tetracycline (tetB, tetC, tetD, and tetR). In particular, tetracycline resistance genes were located on the transposon Tn10-like element. The SSuT element-harboring E. coli can be an important source of the transmission of antimicrobial resistance to other pathogenic bacteria. Therefore, strict sanitary measures in human and animal environments are necessary to prevent the spread of resistant bacteria through fecal residues of wild birds.
Salmonella is one of the most common foodborne pathogens worldwide. Salmonella infections in humans are mainly associated with consumption of poultry products contaminated with this foodborne ...pathogen. Therefore, strict sanitary measures are necessary to control Salmonella contamination during the slaughtering process of poultry. The objective of this study was to determine the occurrence and transmission of Salmonella at a series of steps in the slaughtering process of chicken. A total of 601 samples were collected from a series of slaughtering steps (10 sampling sites) of 26 chicken slaughterhouses throughout Korea. Salmonella was isolated from samples and its distribution was analyzed along the slaughtering process. Isolates from each sampling site were tested for susceptibility to 15 antibiotics by the broth microdilution method. They were also genotypically characterized by pulsed‐field gel electrophoresis (PFGE). Salmonela was isolated from 168 out of 601 samples. Sixteen serotypes were identified while six isolates were untypable. Salmonella enterica serovars Montevideo (n = 29) and Virchow (n = 27) were the most common serotypes out of 119 nonredundant isolates. Relatively high contamination rates of Salmonella were found in shackles (75.0%), feathers near plucking machine (68.5%), and feces from crates (44.0%). Twenty‐three antibiotic resistance patterns were recognized and 40 (33.6%) isolates were resistant to five or more antibiotics. The same serotypes of Salmonella were distributed along the slaughtering process of each Salmonella‐positive slaughterhouse. Most of those isolates belonging to the same serotype had identical or closely related PFGE profiles. They also shared common antibiotic resistance patterns. Overall findings of this study indicated that Salmonella were sequentially transmitted through the chicken slaughtering process.
Practical Application
This study provides useful information on the distribution and transmission of Salmonella serotypes through the chicken slaughtering process. Overall findings indicated the need for routine microbiological monitoring along the slaughtering process. This study also showed that on‐farm control of Salmonella is needed to obtain Salmonella‐free chicken carcasses.
We report the identification of novel highly pathogenic avian influenza viruses of subtype H5N6, clade 2.3.4.4, that presumably originated from China. In addition, reassortant strains with Eurasian ...lineage low pathogenic avian influenza viruses were isolated in wild birds and poultry in South Korea. The emergence of these novel H5N6 viruses and their circulation among bird populations are of great concern because of the potential for virus dissemination with intercontinental wild bird migration.
•Novel highly pathogenic avian influenza viruses of subtype H5N6 were detected in South Korea in 2016.•The Korean H5N6 viruses seem to be likely originated from H5N6 viruses circulating in Guangdong province of China.•Their reassortants with Eurasian lineage low pathogenic avian influenza viruses were isolated in wild birds and poultry.
Salmonellosis is one of the most prevalent foodborne illnesses. The outbreak of this disease is often associated with eggs. In this study, the prevalence and characteristics of Salmonella was ...surveyed in layer farms in Korea. In addition, the risk factors affecting the prevalence of Salmonella in these farms were also assessed. Of the 32 farms and 67 flocks examined, 19 farms (59.3%) and 34 flocks (50.7%) were observed to be positive for Salmonella contamination. Salmonella was detected in the surrounding environment such as feces (41.8%), dust (40.3%), egg shells (17.2%), as well as the internal egg contents (5.2%). The incidence of Salmonella positives were tended to increase when the flock size is larger (P = 0.021). Differences in the provinces also affected Salmonella prevalence (P < 0.001). The most frequently observed Salmonella serovars in the flocks were Salmonella Bareilly (41.2%), Salmonella Mbandaka (32.4%), and Salmonella Rissen (17.6%). Twenty of the flocks revealed multi-serovar contamination, with the isolation of 2 to 4 serovars. Antimicrobial susceptibility testing revealed that 93 out of 101 isolates were susceptible to the 17 tested antimicrobial agents. The remaining isolates displayed resistance to ampicillin (4.0%), nalidixic acid (3.0%), tetracycline (1.0%), cephalothin (1.0%), and gentamicin (1.0%). As human salmonellosis has been repeatedly correlated to the consumption of poultry products worldwide, continuous studies are required to effectively minimize the Salmonella contamination in layer farms and egg products.
Despite the recent promising results of clinical trials using human pluripotent stem cell (hPSC)-based cell therapies for age-related macular degeneration (AMD), the risk of teratoma formation ...resulting from residual undifferentiated hPSCs remains a serious and critical hurdle for broader clinical implementation. To mitigate the tumorigenic risk of hPSC-based cell therapy, a variety of approaches have been examined to ablate the undifferentiated hPSCs based on the unique molecular properties of hPSCs. In the present review, we offer a brief overview of recent attempts at selective elimination of undifferentiated hPSCs to decrease the risk of teratoma formation in hPSC-based cell therapy.
Although it has rapidly decreased since the early 2000s, fowl typhoid still occurs in commercial layer chickens, causing a significant economic loss in Korea. There is growing concern about the ...emergence of new pathogenic strains of the causative agent, Salmonella Gallinarum, which is able to overcome vaccine immunity. It has also been suspected that the poultry red mite, Dermanyssus gallinae, which is commonly found in layer chicken farms, may be an important cause of the recurrence of fowl typhoid in the farms. This study was conducted to examine changes in the virulence of recent isolates of S. Gallinarum obtained from layer farms and estimate the potential of the disease transmission of D. gallinae in the farms. Clinical and environmental samples and mites collected from layer farms affected by fowl typhoid between 2013 and 2018 were tested for S. Gallinarum. The isolates were characterized by genotypic analyses and in vitro virulence assays with chicken-derived cell lines. Vaccine protection against recent isolates was examined in the chickens. A total of 45 isolates of S. Gallinarum were collected and there was no evidence of changes in their virulence. It has also been demonstrated that the S. Gallinarum 9R vaccine strain widely used in Korea is still effective in controlling fowl typhoid if the susceptibility of birds to the disease is not increased by stress. Salmonella Gallinarum isolated from the outer and inner parts of D. gallinae, environmental dust, and dead birds of the same farm showed the same or closely related genotypes. Consequently, the present study indicated that the horizontal transmission and environmental persistence of S. Gallinarum and the increased disease susceptibility of chickens in layer farms could be mediated by D. gallinae, causing persistent outbreaks of fowl typhoid.
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