Characterization and Zoonotic Potential of Uropathogenic Escherichia coli Isolated from Dogs

The aim of this study was to investigate the characteristics of canine uropathogenic Escherichia coli (UPEC) and the interaction between canine UPEC and human bladder epithelial cells. Ten E. coli isolates collected from dogs with cystitis were analyzed for antimicrobial resistance patterns, the presence of virulence factors, and biofilm formation. The ability of these isolates to induce cytotoxicity, invade human bladder epithelial cells, and stimulate an immune response was also determined. We observed a high rate of antimicrobial resistance among canine UPEC isolates. All virulence genes tested (including adhesins, iron acquisition, and protectin), except toxin genes, were detected among the canine UPEC isolates. We found that all isolates showed varying degrees of biofilm formation (mean, 0.26; range, 0.07 to 0.82), using a microtiter plate assay to evaluate biofilm formation by the isolates. Cytotoxicity to human bladder epithelial cells by the canine UPEC isolates increased in a time-dependent manner, with a 56.9% and 36.1% reduction in cell viability compared with the control at 6 and 9 h of incubation, respectively. We found that most canine UPEC isolates were able to invade human bladder epithelial cells. The interaction between these isolates and human bladder epithelial cells strongly induced the production of proinflammatory cytokines such as IL-6 and IL-8. We demonstrated that canine UPEC isolates can interact with human bladder epithelial cells, although the detailed mechanisms remain unknown. The results suggest that canine UPEC isolates, rather than dogspecific pathogens, have zoonotic potential.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000051105/2SEQ:2PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000051105ADJUST_YN:NEMP_ID:A077262DEPT_CD:551CITE_RATE:1.381FILENAME:2013-3 jmb 23(3)422-429.pdfDEPT_NM:수의학과EMAIL:[email protected]_YN:YCONFIRM:

Attenuating the EGFR-ERK-SOX9 axis promotes liver progenitor cell‐mediated liver regeneration in zebrafish

The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver injury settings. In chronic liver diseases, the number of liver progenitor cells (LPCs) correlates proportionally to disease severity, implying that their inefficient differentiation into hepatocytes exacerbates the disease. Moreover, LPCs secrete pro‐inflammatory cytokines; thus, their prolonged presence worsens inflammation and induces fibrosis. Promoting LPC‐to‐hepatocyte differentiation in patients with advanced liver disease, for whom liver transplantation is currently the only therapeutic option, may be a feasible clinical approach since such promotion generates more functional hepatocytes and concomitantly reduces inflammation and fibrosis. Here, using zebrafish models of LPC‐mediated liver regeneration, we present a proof‐of‐principle of such therapeutics by demonstrating a role for the EGFR signaling pathway in differentiation of LPCs into hepatocytes. We found that suppression of EGFR signaling promoted LPC‐to‐hepatocyte differentiation via the MEK‐ERK‐SOX9 cascade. Pharmacological inhibition of EGFR or MEK/ERK promoted LPC‐to‐hepatocyte differentiation as well as genetic suppression of the EGFR‐ERK‐SOX9 axis. Moreover, Sox9b overexpression in LPCs blocked their differentiation into hepatocytes. In the zebrafish liver injury model, both hepatocytes and biliary epithelial cells contributed to LPCs. EGFR inhibition promoted the differentiation of LPCs regardless of their origin. Notably, short‐term treatment with EGFR inhibitors resulted in better liver recovery over the long term. Conclusion: The EGFR‐ERK‐SOX9 axis suppresses LPC‐to‐hepatocyte differentiation during LPC‐mediated liver regeneration. We suggest EGFR inhibitors as a pro‐regenerative therapeutic drug for patients with advanced liver disease

Ticks Collected from Selected Mammalian Hosts Surveyed in the Republic of Korea During 2008-2009

A tick survey was conducted to determine the relative abundance and distribution of ticks associated with selected mammals in the Republic of Korea (ROK) during 2008-2009. A total of 918 ticks were collected from 76 mammals (6 families, 9 species) captured at 6 provinces and 3 Metropolitan Cities in ROK. Haemaphysalis longicornis (54.4%) was the most frequently collected tick, followed by Haemaphysalis flava (28.5%), Ixodes nipponensis (7.6%), Ixodes pomerantzevi (4.8%), Ixodes persulcatus (4.6%), and Haemaphysalis japonica (0.1%). Adults (57.0%) and nymphs (28.7%) of Ixodes and Haemaphysalis spp. were collected most frequently from medium or large mammals in this survey, while few larvae (14.3%) were collected. Hydropotes inermis was the most frequently captured mammal (52.6%), with a 16.4 tick index and 5 of 6 species of ticks collected during this survey. H. longicornis (69.7%) was the predominant tick collected from H. inermis, followed by H. flava (22.2%), I. persulcatus (6.1%), I. nipponensis (1.8%), and H. japonica (0.2%)

Empagliflozin Contributes to Polyuria via Regulation of Sodium Transporters and Water Channels in Diabetic Rat Kidneys

Besides lowering glucose, empagliflozin, a selective sodium-glucose cotransporter-2 (SGLT2) inhibitor, have been known to provide cardiovascular and renal protection due to effects on diuresis and natriuresis. However, the natriuretic effect of SGLT2 inhibitors has been reported to be transient, and long-term data related to diuretic change are sparse. This study was performed to assess the renal effects of a 12-week treatment with empagliflozin (3 mg/kg) in diabetic OLETF rats by comparing it with other antihyperglycemic agents including lixisenatide (10 μg/kg), a glucagon-like peptide receptor-1 agonist, and voglibose (0.6 mg/kg), an α-glucosidase inhibitor. At 12 weeks of treatment, empagliflozin-treated diabetic rats produced still high urine volume and glycosuria, and showed significantly higher electrolyte-free water clearance than lixisenatide or voglibose-treated diabetic rats without significant change of serum sodium level and fractional excretion of sodium. In empagliflozin-treated rats, renal expression of Na+-Cl- cotransporter was unaltered, and expressions of Na+/H+ exchanger isoform 3, Na+-K+-2Cl- cotransporter, and epithelial Na+ channel were decreased compared with control diabetic rats. Empagliflozin increased an expression of aquaporin (AQP)7 but did not affect AQP3 and AQP1 protein expressions in diabetic kidneys. Despite the increased expression in vasopressin V2 receptor, protein and mRNA levels of AQP2 in empagliflozin-treated diabetic kidneys were significantly decreased compared to control diabetic kidneys. In addition, empagliflozin resulted in the increased phosphorylation of AQP2 at S261 through the increased cyclin-dependent kinases 1 and 5 and protein phosphatase 2B. These results suggest that empagliflozin may contribute in part to polyuria via its regulation of sodium channels and AQP2 in diabetic kidneys

Prevalence of tick-borne encephalitis virus in ticks from southern Korea

The prevalence of tick-borne encephalitis virus (TBEV) in southern Korea was determined by collecting ticks using tick drags. A total of 4,077 of 6,788 ticks collected were pooled (649 pools) according to collection site, species, and developmental stage and assayed for TBEV. The TBEV protein E and NS5 gene fragments were detected using RT-nested PCR in six pools of nymphs collected from Jeju Island (2,491 ticks). The minimum field detection rates for TBEV were 0.17% and 0.14% for Haemaphysalis longicornis and Haemayphysalis flava nymphs, respectively. The 252 bp NS5 and 477 bp protein E gene amplicons were sequenced. Phylogenetic analysis showed that the NS5 and protein E genes of the Jeju strain were clustered with Western subtype (98.0% and 99.4% identity, respectively). The Western subtype of TBEV is endemic in Korea, including Jeju Island. The study of vector and zoonotic host susceptibility to TBEV is required to better understand its potential impact on public health

First Report for the Seasonal and Annual Prevalence of Flea-Borne Bartonella from Rodents and Soricomorphs in the Republic of Korea

Rodents and soricomorphs are animal hosts of fleas and associated zoonotic microbial pathogens. A total of 4,889 small mammals were collected from Gyeonggi and Gangwon Provinces, Republic of Korea, from 2008 through 2010, including: Apodemus agrarius (4,122, 84.3%), followed by Crocidura lasiura (282, 5.8%), Microtus fortis (257, 5.3%), Myodes regulus (77, 1.6%), Micromys minutus (71, 1.5%), Mus musculus (63, 1.3%), and 4 other species (17, 0.3%). A total of 1,099 fleas belonging to 10 species and 7 genera were collected. Ctenophthalmus congeneroides (724, 65.9%) was the most commonly collected flea, followed by Stenoponia sidimi (301, 27.4%), Neopsylla bidentatiformis (29, 2.6%), and Rhadinopsylla insolita (25, 2.3%). The remaining species accounted for only 1.8% (20, range 1-6) of all fleas collected. The 2 dominant flea species, C. congeneroides and S. sidimi, showed an inverse seasonal pattern, with higher populations of C. congeneroides from January-September, whereas S. sidimi was more frequently collected during October-December. The overall flea infestation rates (FIR) and flea indices (FI) were 14.1% and 0.22, respectively, and were highest during April-June (19.7% and 0.30, respectively). A total of 735 of the 1,099 fleas were assayed for the detection of Bartonella spp. by PCR using Bartonella-specific primers, of which 515 were positive for Bartonella, with an overall maximum likelihood estimate (MLE) of 700.7/1,000. The highest MLE values were observed during April-June (899.2) and July-September (936.2) trapping periods and, although lower, were similar for January-March (566.7) and October-December (574.1). C. congeneroides demonstrated high MLEs for all seasons (range 752.5-934.8), while S. sidimi was positive for Bartonella only during January-March (MLE = 342.1) and October-December (MLE = 497.2) collection periods. Continued long-term surveillance of small mammals and associated ectoparasites is needed to improve our understanding of the prevalence of Bartonella spp. in fleas and the role of fleas in the zoonotic maintenance and transmission of Bartonella to humans.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000051105/5SEQ:5PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000051105ADJUST_YN:YEMP_ID:A077262DEPT_CD:551CITE_RATE:2.277FILENAME:2013 vbz 13(7)457-467 flea-borne bartonella.pdfDEPT_NM:수의학과SCOPUS_YN:YCONFIRM:

Development of a neutralization monoclonal antibody with a broad neutralizing effect against SARS-CoV-2 variants

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has challenged the effectiveness of current therapeutic regimens. Here, we aimed to develop a potent SARS-CoV-2 antibody with broad neutralizing effect by screening a scFv library with the spike protein receptor-binding domain (RBD) via phage display. Methods SKAI-DS84 was identified through phage display, and we performed pseudovirus neutralization assays, authentic virus neutralization assays, and in vivo neutralization efficacy evaluations. Furthermore, surface plasmon resonance (SPR) analysis was conducted to assess the physical characteristics of the antibody, including binding kinetics and measure its affinity for variant RBDs. Results The selected clones were converted to human IgG, and among them, SKAI-DS84 was selected for further analyses based on its binding affinity with the variant RBDs. Using pseudoviruses, we confirmed that SKAI-DS84 was strongly neutralizing against wild-type, B.1.617.2, B.1.1.529, and subvariants of SARS-CoV-2. We also tested the neutralizing effect of SKAI-DS84 on authentic viruses, in vivo and observed a reduction in viral replication and improved lung pathology. We performed binding and epitope mapping experiments to understand the mechanisms underlying neutralization and identified quaternary epitopes formed by the interaction between RBDs as the target of SKAI-DS84. Conclusions We identified, produced, and tested the neutralizing effect of SKAI-DS84 antibody. Our results highlight that SKAI-DS84 could be a potential neutralizing antibody against SARS-CoV-2 and its variants.This work was supported by the National Research Foundation of Korea (NRF-2021R1F1A1055906, NRF-2014M3A9D5A01075128, 2021M3H9A1030260) grant funded by the Korea government (MSIT). This research was supported by the R&D Project for the Improvement of Science and Industrial Technology in Gwangwon-do (2022-DD-UP-0287

Effect of shared decision-making education on physicians’ perceptions and practices of end-of-life care in Korea

Background Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians’ perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea. Methods A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals. Results A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low. Conclusion The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required