Publications by authors named "Kwong-Chung Tung"

65 Publications

Nesfatin-1 facilitates IL-1β production in osteoarthritis synovial fibroblasts by suppressing miR-204-5p synthesis through the AP-1 and NF-κB pathways.

Aging (Albany NY) 2021 Sep 24;13(18):22490-22501. Epub 2021 Sep 24.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

The progression of osteoarthritis (OA) is mediated by adipokines, one of which is nesfatin-1, which is responsible for the production of inflammatory cytokines. However, how this molecule may affect the synthesis of the proinflammatory cytokine interleukin 1 beta (IL-1β) in OA is unclear. Our analyses of records from the Gene Expression Omnibus (GEO) dataset and clinical specimens of synovial tissue revealed higher levels of nesfatin-1 and IL-1β in OA samples compared with normal healthy tissue. We found that nesfatin-1 facilitates IL-1β synthesis in human OA synovial fibroblasts (OASFs) and suppresses the generation of micro-RNA (miR)-204-5p, as the miR-204-5p levels in OA patients were lower than those in healthy controls. Nesfatin-1-induced stimulation of IL-1β in human OASFs occurred via the suppression of miR-204-5p synthesis by the PI3K, Akt, AP-1 and NF-κB pathways. We suggest that nesfatin-1 is worth targeting in OA treatment.
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http://dx.doi.org/10.18632/aging.203559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507299PMC
September 2021

Colonization dynamics of Klebsiella pneumoniae in the pet animals and human owners in a single household.

Vet Microbiol 2021 May 23;256:109050. Epub 2021 Mar 23.

Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address:

Klebsiella pneumoniae resides in the gastrointestinal (GI) microbiota of humans and animals. To characterize the population dynamics of GI-colonizing K. pneumoniae, we examined the clonality of K. pneumoniae isolates, which were longitudinally collected from the fecal samplings of a healthy married couple and their pet animals during Sep. 2015 to Oct. 2016. As revealed by XbaI-PFGE analysis, the K. pneumoniae populations detected in the male owner and in one of the dogs, consisted of clonally diverse K. pneumoniae isolates; whereas, a dominant clone persisted in the GI tract of the female owner who was prone to chronic diarrhea. Whole-genome sequencing analysis of a representative strain of this pathobiont clone revealed a sequence type (ST) 29 lineage with the carriage of KL54 cps locus and a 192,603 bp IncHIB-type virulence plasmid. After probiotics intervention, the pathobiont K. pneumoniae diminished. The vacant niche was transiently occupied by other clones of K. pneumoniae, one of which was also present in the male owner. Besides the dog, the fecal carriage of K. pneumoniae was also detected in a pet turtle. This turtle isolate was resistant to multiple antimicrobials, including carbapenems. Possible transmission of drug-resistant K. pneumoniae through human-pet bonds warrants our attention.
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http://dx.doi.org/10.1016/j.vetmic.2021.109050DOI Listing
May 2021

Genomic investigation of emerging zoonotic pathogen .

Ci Ji Yi Xue Za Zhi 2020 Apr-Jun;32(2):162-166. Epub 2019 Jun 13.

Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.

Objective: is an emerging zoonotic pathogen commonly found in aquatic ecosystem. Clustered regularly interspaced short palindromic repeats (CRISPR) and (CRISPR)-associated gene systems act as adaptive immune system of prokaryotes. Recently, growing evidence suggested their role in bacterial virulence and resistance. Despite its medical importance, little is known about the genomic characteristics of .

Materials And Methods: Strain ZYW6 was isolated from . We sequenced the 16S rRNA gene and blast against the GenBank bacterial database. Antibiotic susceptibility tests and interpretation were performed by automatic VITEK 2 system. We extracted the genomic DNA with QIAGEN Genomic-tip 100/G kit and QIAGEN Genomic DNA Buffer Set. Whole-genome shotgun sequencing was performed using the Illumina MiSeq sequencer. To identify the CRISPR-Cas System in the genome of ZYW6, the Integrated Microbial Genomes and Microbiomes and CRISPRFinder were used.

Results: We characterized the genome of a strain. The genome is 4,765,190 bp in length and encodes 4262 open-reading frames. Type I CRISPR-Cas system and serine biosynthesis genes were identified.

Conclusion: Our results demonstrate the genetic structure of CRISPR-Cas system, l-serine synthesis, and oxacillinase in . The report of antibiotics resistance genes in the study might indicate a possible reservoir of antimicrobial drug resistance determinants in food animal, resulting in potential infection source. The findings provide insights into the structure and composition of CRISPR-Cas system in and foundation for future biological validation.
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http://dx.doi.org/10.4103/tcmj.tcmj_69_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137373PMC
June 2019

Genome Sequence of Colistin-Resistant Bacteremic Carrying the Beta-Lactamase Gene .

Can J Infect Dis Med Microbiol 2019 10;2019:3840563. Epub 2019 Jun 10.

Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.

is an emerging pathogen widely distributed in aquatic environment. Bacteremia is a major manifestation of infections, and there are increasing reports of antibiotic-resistant strains. However, little is known about the genomic characteristics of human bacteremic . Here, we report the results of the whole-genome sequencing of colistin-resistant TYL, a blood isolate. Chromosome-encoded associated with colistin resistance and gene intrinsic to was identified. Continuous surveillance for the emergence of . is needed.
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http://dx.doi.org/10.1155/2019/3840563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590586PMC
June 2019

Thirteen-Week Oral Toxicity Evaluation of Erinacine AEnriched Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Mycelia in Sprague-Dawley Rats.

Int J Med Mushrooms 2019 ;21(4):401-411

College of Veterinary Medicine, National Chung Hsing University, Taichung City, Taiwan.

Recently, erinacine A-enriched Hericium erinaceus (EAHE) mycelia have demonstrated therapeutic efficacy in animal models of neurodegenerative disease, including Alzheimer and Parkinson disease. Despite promising results from animal models, there have been no reports on its toxicity after long-term consumption. Hence, the present study was designed to evaluate the safety of EAHE mycelia through a 13-week subchronic rodent feeding study. Following 13 weeks of EAHE mycelia feeding at dosages of 0, 875, 1750, and 2625 mg/kg body weight in both male and female Sprague-Dawley rats, findings revealed neither any mortalities nor noticeable toxicological effects in all the rats during the investigation period. Physiological parameters including body weight and feed consumption patterns were unaffected by EAHE mycelia administration. The hematological and biochemical parameters as well as histopathological studies revealed no significant differences between the treatment and control groups. Conclusively, the obtained results suggested that EAHE mycelia could be relatively unharmful when used over an extended period, supporting its safe use in food preparation.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2019030320DOI Listing
August 2019

Genomic and phylogenetic characterization of Shewanella xiamenensis isolated from giant grouper (Epinephelus lanceolatus) in Taiwan.

Zoonoses Public Health 2019 09 12;66(6):679-685. Epub 2019 Apr 12.

Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung City, Taiwan.

Shewanella xiamenensis is an emerging pathogen causing intra-abdominal infection and intestinal colonization. Epidemiologic clues suggest its role as a potential food-borne zoonotic agent. To date, four genome sequences of S. xiamenensis have been made publicly available. All of them were isolated from water samples. In this study, we characterized the genome of a S. xiamenensis strain isolated from a giant grouper in Taiwan. The genome of S. xiamenensis ZYW1 is 4,827,717 bp in length and encodes 4,239 open reading frames. Its genomic sequence shares high homology with other S. xiamenensis strains. bla was identified. This is the first detection of S. xiamenensis in Taiwan. These genomic data and analyses contribute to our understanding of S. xiamenensis and may help to elucidate disease-causing mechanisms in future studies.
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http://dx.doi.org/10.1111/zph.12580DOI Listing
September 2019

Whole-genome characterization of Shewanella algae strain SYT3 isolated from seawater reveals insight into hemolysis.

Future Microbiol 2018 12 27;13:1709-1717. Epub 2018 Nov 27.

Department of Physical Therapy, Shu-Zen Junior College of Medicine & Management, Kaohsiung City 82144, Taiwan.

Aim: To describe the genomic characteristics of seawater-borne hemolytic Shewanella algae and its resistance genes.

Materials & Methods: Whole genome sequence of S. algae SYT3 was determined using llumina MiSeq platform. Multiple-database-based analysis was performed to identify the genetic background of its hemolytic activity and the antibiotic resistance genes.

Results: S. algae SYT3 possesses a homolog of the hly operon involved in the synthesis of hemolysin. We also identified candidate genes associated with resistance to β-lactam antibiotics (bla ) and fluoroquinolone (qnrA3).

Conclusion: The study provides an insight into the hemolytic activity of S. algae. Our findings also suggested S. algae as a potential reservoir of antimicrobial resistance determinants.
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http://dx.doi.org/10.2217/fmb-2018-0267DOI Listing
December 2018

The Pathogenicity of and Ability to Tolerate a Wide Range of Temperatures and Salinities.

Can J Infect Dis Med Microbiol 2018 27;2018:6976897. Epub 2018 Sep 27.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

is a rod-shaped Gram-negative marine bacterium frequently found in nonhuman sources such as aquatic ecosystems and has been shown to be the pathogenic agent in various clinical cases due to the ingestion of raw seafood. The results of this study showed that was present in approximately one in four samples, including water and shellfish samples. Positive reactions (API systems) in strains were seen for gelatinase (gelatin); however, negative reactions were found for indole production (tryptophan). is adapted to a wide range of temperatures (4°C, 25°C, 37°C, and 42°C) and salinity. Temperature is a key parameter in the pathogenicity of as it appears to induce hemolysis at 25°C and 37°C. exhibits pathogenic characteristics at widely varying temperatures, which suggests that it may have the ability to adapt to climate change.
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http://dx.doi.org/10.1155/2018/6976897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180972PMC
September 2018

Genome characterization of bile-isolated ACCC.

Gut Pathog 2018 18;10:38. Epub 2018 Sep 18.

Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, 82144 Taiwan.

Background: has been recognized as an emerging human pathogen. However, not much is known about the mechanism of its pathogenesis and its adaptation to a special niche such as the hepatobiliary tract.

Results: In this study, we isolated the ACCC strain from human bile and performed whole genome sequencing. ACCC consists of a circular 4,743,354-bp chromosome with a GC content of 53.08%, within 4080 protein coding sequences. The genome of strain ACCC contains a number of candidate genes which have been reported to be associated with bile adaption, including , , , and regulon.

Conclusions: Our results highlight the association of with a rare disease profile. Further studies are needed to shed light on the evolution of pathogenesis and the niche adaptation of .
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http://dx.doi.org/10.1186/s13099-018-0267-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145196PMC
September 2018

Volatile Oils of (Jing Jie) as an Alternative Medicine against Multidrug-Resistant Pathogenic Microbes.

Can J Infect Dis Med Microbiol 2018 11;2018:8347403. Epub 2018 Apr 11.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

Essential oils from the dried spikes of (Benth) are obtained by steam distillation. Pulegone was identified as the main component in the spikes of through analysis, with greater than 85% purity obtained in this study. The essential oils are extremely active against all Gram-positive and some Gram-negative reference bacteria, particularly , , and . The minimum inhibitory concentration was found to be between 0.08 and 0.78% (against ), 0.39 and 0.78% (against ), and 0.097 and 0.39% (against ), whereas the minimum bactericidal concentration varied in range from 0.097% to 1.04%. In general, the essential oils show a strong inhibitory action against all tested reference strains and clinical isolates. However, the antibacterial activity of EOs against both reference strains and clinical isolates was relatively lower than other Gram-negative pathogens. The essential oils of also displayed bactericidal activities (MBC/MIC < 4) in this study. These findings reflect the bactericidal activity of the essential oils against a wide range of multidrug-resistant clinical pathogens in an in vitro study. In addition, we propose the fragmentation pathways of pulegone and its derivatives by LC-ESI-MS/MS in this study.
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http://dx.doi.org/10.1155/2018/8347403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925154PMC
April 2018

Effects of non-thermal plasma on sandblasted titanium dental implants in beagle dogs.

J Chin Med Assoc 2018 Oct 31;81(10):920-925. Epub 2018 May 31.

School of Dentistry, National Yang-Ming University, Taipei, Taiwan, ROC; Show Chwan Memorial Hospital, Changhua, Taiwan, ROC. Electronic address:

Background: In this study, we investigated the effects of treating dental implants made from titanium with argon based non-thermal plasma, immediately before insertion on implant stability and bone formation. Biodegradable sandblasting and acid etching had been previously used to modify the surface of the implants.

Methods: To obtain data for 4-time points in triplicate with references, a total of 36 dental implants were divided into 2 groups; 18 implants served as the experimental group and received a spray containing non-thermal plasma, while the other 18 implants served as controls. Two treated and two untreated implants were each inserted in the jaws of 9 beagle dogs. After periods of 4, 8, and 12 weeks, the Implant Stability Quotient scores were determined and histometric values obtained.

Results: Plasma spray treatment increased the healing time slightly during the early recovery period (4th to 8th week, p = 0.1595 and 0.1041, respectively), but was not profoundly effective in the later recovery stage (12th week, p = 0.4942). Both non-decalcified histometric measurements and bone growth analysis showed no statistically significant differences between the plasma spray group and the controls at 4, 8, and 12 weeks.

Conclusion: Non-thermal plasma did not enhance the stability of the implants nor did it increase bone formation in our animal models.
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http://dx.doi.org/10.1016/j.jcma.2018.03.004DOI Listing
October 2018

Draft genome sequence of CTX-M-type β-lactamase-producing Klebsiella quasipneumoniae subsp. similipneumoniae isolated from a Box turtle.

J Glob Antimicrob Resist 2018 03 29;12:235-236. Epub 2017 Dec 29.

Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan. Electronic address:

Objectives: Klebsiella spp. are regarded as major pathogens causing infections in humans and various animals. Here we report the draft genome sequence of a CTX-M-type β-lactamase-producing Klebsiella quasipneumoniae subsp. similipneumoniae strain CHKP0062 isolated from a Yellow-margined Box turtle.

Methods: An Illumina-Solexa platform was used to sequence the genome of CHKP0062. Qualified reads were assembled de novo using Velvet. The draft genome was annotated by the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). The resistome and virulome of the strain were investigated.

Results: A total of 5423 protein-coding sequences, 87 tRNAs, 24 rRNAs and 12 ncRNAs were identified in the 5 699 275-bp genome. CHKP0062 was assigned to sequence type ST2131 with the K-loci type as KL67. No virulence-associated genes were identified. However, numerous antimicrobial resistance genes were present in this strain. Plasmid contigs were assembled and revealed homology to the multidrug resistance plasmids pC15-K, pCTX-M3 and pKF3-94, with the carriage of the class A β-lactamase genes bla and bla.

Conclusion: The genome sequence reported in this study will be useful for comparative genomic analysis regarding the dissemination of clinically important antibiotic resistance genes among Klebsiella spp. isolated from humans and animals.
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http://dx.doi.org/10.1016/j.jgar.2017.12.012DOI Listing
March 2018

Colistin Resistance of Isolated from Snakes in Taiwan.

Can J Infect Dis Med Microbiol 2017 25;2017:7058396. Epub 2017 Sep 25.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.

This study included fifty-eight isolates of from the oral cavity of snakes that were recruited from clinical cases, captive and wild snakes. The minimum inhibitory concentrations (MICs) for the determination of susceptibility were identified by the broth microdilution method. Polymerase chain reaction (PCR) was employed to detect -lactamases genes. With regard to antipseudomonal antibiotics, the lowest nonsusceptible rates were in aztreonam (15%), piperacillin/tazobactam (12%), and amikacin (9%). The nonsusceptible rates were high in gentamicin (33%) and colistin (55%). Meanwhile, presented in 100% of isolates where , , and came at 94.8%, 89.7%, and 27.6%, respectively. Emergence of multidrug resistant (MDR) strains and colistin-resistant strains highlights the potential breach of public health as could be transmitted through either direct contact or indirect dissemination through the environment. This study reports that the highly resistant from snakes' oral cavity were discovered for the very first time in Taiwan.
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http://dx.doi.org/10.1155/2017/7058396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632879PMC
September 2017

Effect of a nonthermal-atmospheric pressure plasma jet on wound healing: An animal study.

J Chin Med Assoc 2016 Jun 29;79(6):320-8. Epub 2016 Mar 29.

College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC. Electronic address:

Background: The use of a nonthermal plasma (NTP) jet in the treatment of living tissue has been the subject of considerable interest in the field of medical technology, and has the potential to reduce the recovery time of open wounds. We aimed to investigate the wound-healing process by clinical observation, blood tests, and expression of cell adhesion markers and reactive oxygen species in NTP jet-treated rats.

Methods: This study utilized Sprague-Dawley (SD) rats as experimental subjects, and wounds measuring 2 cm × 2 cm were produced on the animals' backs. The experimental group was treated with NTP for 5 min/d for 4 weeks. The NTP was injected in a diffused manner into the cage housing the rats. The SD rats that had not received plasma treatment were designated as the control group. Blood was drawn on Postoperative Day 2, Day 4, and at 3 months. An immunohistochemical stain of E-cadherin and 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species marker, were evaluated and quantified for analysis using a CMYK color model.

Results: A total of 35 SD rats were included in the study (25 in the NTP group and 10 in the control group). Low dose plasma treatment shortened the wound-healing time without damaging organs. In the NTP group, the white blood cell counts at Day 2 post-NTP treatment was not increased significantly more than that in the control group. After quantification of immunohistochemical staining, 4-HNE was increased at Day 14 compared with Day 7 (16.16 ± 12.81% vs. 55.11 ± 8.11%, p < 0.001), and E-cadherin was also increased (52.17 ± 14.96% vs. 70.46 ± 12.78%, p = 0.04) in the NTP group. After comparison of NTP and the control, it was observed that 4-HNE and E-cadherin were increased in the NTP group on Day 14.

Conclusion: Short-term, low-dose NTP wound treatment was demonstrated to accelerate wound healing in SD rats without vital organ toxicity.
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http://dx.doi.org/10.1016/j.jcma.2015.06.024DOI Listing
June 2016

WISP-1 promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-300 in human oral squamous cell carcinoma cells.

Oncotarget 2016 Mar;7(9):9993-10005

Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.

Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by a poor prognosis and a low survival rate. Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis and is correlated with cancer metastasis. WNT1-inducible signaling pathway protein-1 (WISP)-1/CCN4 is an extracellular matrix-related protein that belongs to the CCN family and stimulates many biological functions. Our previous studies showed that WISP-1 plays an important role in OSCC migration and angiogenesis. However, the effect of WISP-1 on VEGF-C regulation and lymphangiogenesis in OSCC is poorly understood. Here, we showed a correlation between WISP-1 and VEGF-C in tissue specimens from patients with OSCC. To examine the lymphangiogenic effect of WISP-1, we used human lymphatic endothelial cells (LECs) to mimic lymphatic vessel formation. The results showed that conditioned media from WISP-1-treated OSCC cells promoted tube formation and cell migration in LECs. We also found that WISP-1-induced VEGF-C is mediated via the integrin αvβ3/integrin-linked kinase (ILK)/Akt signaling pathway. In addition, the expression of microRNA-300 (miR-300) was inhibited by WISP-1 via the integrin αvβ3/ILK/Akt cascade. Collectively, these results reveal the detailed mechanism by which WISP-1 promotes lymphangiogenesis via upregulation of VEGF-C expression in OSCC. Therefore, WISP-1 could serve as therapeutic target to prevent metastasis and lymphangiogenesis in OSCC.
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http://dx.doi.org/10.18632/oncotarget.7014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891098PMC
March 2016

Characteristics of visual fatigue under the effect of 3D animation.

Technol Health Care 2015 ;24 Suppl 1:S231-5

Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.

Visual fatigue is commonly encountered in modern life. Clinical visual fatigue characteristics caused by 2-D and 3-D animations may be different, but have not been characterized in detail. This study tried to distinguish the differential effects on visual fatigue caused by 2-D and 3-D animations. A total of 23 volunteers were subjected to accommodation and vergence assessments, followed by a 40-min video game program designed to aggravate their asthenopic symptoms. The volunteers were then assessed for accommodation and vergence parameters again and directed to watch a 5-min 3-D video program, and then assessed again for the parameters. The results support that the 3-D animations caused similar characteristics in vision fatigue parameters in some specific aspects as compared to that caused by 2-D animations. Furthermore, 3-D animations may lead to more exhaustion in both ciliary and extra-ocular muscles, and such differential effects were more evident in the high demand of near vision work. The current results indicated that an arbitrary set of indexes may be promoted in the design of 3-D display or equipments.
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http://dx.doi.org/10.3233/THC-151079DOI Listing
September 2016

Complete Genome Sequence of Campylobacter fetus subsp. testudinum Strain Pet-3, Isolated from a Lizard (Hydrosaurus pustulatus).

Genome Announc 2015 Feb 19;3(1). Epub 2015 Feb 19.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

The whole-genome sequence for Campylobacter fetus subsp. testudinum, a pathogen isolated from humans and turtles, has been reported recently. We present another completed genome sequence of the C. fetus subsp. testudinum strain pet-3, which was isolated from a lizard in Taiwan, for further genomic comparison study.
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http://dx.doi.org/10.1128/genomeA.01420-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335325PMC
February 2015

The different molecular forms of urine neutrophil gelatinase-associated lipocalin present in dogs with urinary diseases.

BMC Vet Res 2014 Aug 27;10:202. Epub 2014 Aug 27.

Institute of Veterinary Clinical Science, School of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, No,1, Sec,4, Roosevelt Rd, Taipei, Taiwan.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for the early prediction of renal diseases. NGAL may exist as monomer, dimer and/or NGAL/MMP-9 complex forms in humans. In this study, the existence of various forms of NGAL in urine (uNGAL) was determined and whether these forms are related to the different urinary diseases found in dogs is further discussed.

Results: Eighty-one urine samples from dogs with different forms of renal disease (41), pyuria (19) and a number of non-renal related diseases (10), as well as healthy dogs (11), were collected. uNGAL concentrations and their molecular forms in dogs were measured by ELISA and Western blot analysis, respectively. The uNGAL concentrations of dogs with pyuria (median: 15.35 ng/mL) were significantly higher than those of the healthy control animals (median: 3.92 ng/mL) (p < 0.01), but lower than those of dogs with renal diseases (median: 23.77 ng/mL). Each NGAL molecular form could be detected in dog urine. In particular, monomer was detected more frequently in patients with renal disease than those with non-renal diseases; while the dimer form appeared in a significantly higher percentage of cases with pyuria compared to those without pyuria. The NGAL/MMP-9 complex was found to exist not only in the patients with cystitis, but also in the cases with renal injury.

Conclusion: Different molecular forms of uNGAL can indicate different origins of the urinary abnormalities. Determining the molecular forms of uNGAL present in diseased dogs may provide clinical workers with a tool that will help the early and more precise detection of different urinary diseases.
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http://dx.doi.org/10.1186/s12917-014-0202-yDOI Listing
August 2014

Antimicrobial resistance to cefotaxime and ertapenem in Enterobacteriaceae: the effects of altering clinical breakpoints.

J Infect Dev Ctries 2014 Mar 13;8(3):289-96. Epub 2014 Mar 13.

Taichung Veterans General Hospital, Taichung, Taiwan.

Introduction: The Clinical and Laboratory Standards Institute (CLSI) updated its antimicrobial susceptibility testing interpretation criteria for Enterobacteriaceae. This study assessed the effects of clinical breakpoint changes in the CLSI 2009 to 2012 guidelines on antibiotic susceptibility testing reports.

Methodology: In total, 2,076 non-duplicate clinical isolates of Enterobacteriaceae were analyzed. The disk diffusion method was used for susceptibility testing. The CLSI 2009-12 clinical breakpoints were applied to determine susceptibility of cefotaxime and ertapenem. Combined-disk testing was used for phenotypic confirmation of extended-spectrum beta-lactamase (ESBL) production.

Results: In total, Enterobacteriaceae resistance rates to cefotaxime increased from 13.1% using the CLSI 2009 guidelines to 23.6% with the CLSI 2010-12 guidelines, and the resistance rates to ertapenem were 0.4%, 1.0% and 0.8% with CLSI 2009, 2011 and 2012, respectively. Based on the 2010-12 CLSI criteria, all ESBL-producing Escherichia coli and Klebsiella pneumoniae were resistant to cefotaxime. Marked differences in susceptibility to ertapenem between the 2009 CLSI criteria and 2012-12 CLSI criteria were noted in ESBL-producing K. pneumoniae.

Conclusions: Breakpoints changes in the updated CLSI guidelines resulted in higher resistance rates to cefotaxime and ertapenem. In addition, the effects were different in individual Enterobacteriaceae species. As a result, clinicians may opt to use alternative antimicrobial agents. Upon implementation of the newer CLSI guidelines, laboratories should be aware of the possible consequences and closely monitor the effects.
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http://dx.doi.org/10.3855/jidc.3335DOI Listing
March 2014

Cobra bite wound infection caused by Shewanella algae.

Int J Infect Dis 2014 Mar 2;20:11-2. Epub 2013 Oct 2.

College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan. Electronic address:

Shewanella wound infections after snake bites are rare. We report the case of a Shewanella algae wound infection associated with a cobra bite in a 27-year-old woman. The isolate was confirmed by sequencing of the 16S ribosomal DNA gene. This case expands the reported spectrum of infection caused by S. algae and raises the possibility that S. algae could be a causative pathogen in wound infections resulting from snake bites.
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http://dx.doi.org/10.1016/j.ijid.2013.08.014DOI Listing
March 2014

Liver abscess caused by Klebsiella pneumoniae in a red-footed tortoise.

J Microbiol Immunol Infect 2015 Jun 13;48(3):347-9. Epub 2014 Feb 13.

Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC. Electronic address:

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http://dx.doi.org/10.1016/j.jmii.2013.12.004DOI Listing
June 2015

Activation of hepatic inflammatory pathways by catecholamines is associated with hepatic insulin resistance in male ischemic stroke rats.

Endocrinology 2014 Apr 17;155(4):1235-46. Epub 2014 Jan 17.

Division of Family Medicine (Y.Y.W.), Division of Endocrinology and Metabolism (S.Y. L., Y.H.C., W.H.H.S.), Department of Medical Research (C.J.C.), Taichung Veterans General Hospital, Taichung, Taiwan; and Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan (Y.Y.W., K.C.T.); and School of Medicine, National Yang Ming University, Taipei, Taiwan (Y.Y.W, S.Y.L., W.H.H.S.).

Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes. In the current study we determined the effects of acute stroke on hepatic insulin signaling, TNF-α expression, endoplasmic reticulum (ER) stress, the activities of c-Jun N-terminal kinase (JNK), inhibitor κB kinase β (IKK-β), and nuclear factor-κB (NF-κB) pathways. Rats with cerebral ischemia developed higher blood glucose, and insulin levels, and insulin resistance index, as well as hepatic gluconeogenic enzyme expression compared with the sham-treated group. The hepatic TNF-α mRNA and protein levels were elevated in stroke rats in association with increased ER stress, phosphorylation of JNK1/2 and IKK-β proteins, IκB/NF-κB signaling, and phosphorylation of insulin receptor-1 (IRS-1) at serine residue. The basal and insulin-stimulated tyrosine phosphorylation of IRS-1 and AKT proteins was reduced. In addition, acute stroke increased circulating catecholamines in association with hepatic adrenergic signaling activation. After administration of a nonselective β-adrenergic receptor blocker (propranolol) before induction of cerebral ischemic injury, hepatic adrenergic transduction, TNF-α expression, ER stress, and the activation of the JNK1/2, IKK-β, and NF-κB pathways, and serine phosphorylation of IRS-1 were all attenuated. In contrast, the phosphorylated IRS-1 at tyrosine site and AKT levels were partially restored with improved poststroke hyperglycemia and insulin resistance index. These results suggest that acute ischemic stroke can activate proinflammatory pathways in the liver by the catecholamines and is associated with the development of hepatic insulin resistance.
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http://dx.doi.org/10.1210/en.2013-1593DOI Listing
April 2014

Clinical and microbiological features of shewanella bacteremia in patients with hepatobiliary disease.

Intern Med 2013 15;52(4):431-8. Epub 2013 Feb 15.

Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan.

Objective: Shewanella bacteremia is an uncommon but potentially fatal disease. Although hepatobiliary diseases have been proposed to be risk factors for various Shewanella infections, little is known about the features of Shewanella bacteremia in patients with hepatobiliary diseases. This study aims to characterize the presentation and risk factors of Shewanella bacteremia in patients with hepatobiliary diseases.

Methods: We retrospectively investigated the clinical features, microbiology and outcomes of patients with Shewanella bacteremia who were admitted to a tertiary medical center between January 2001 and December 2010. All isolates were confirmed to the species level using 16S rRNA sequencing analyses. The English language medical literature was searched for previously published reports.

Results: Fifty-nine cases of Shewanella bacteremia, including nine at the hospital, were identified, 28 (47.4%) of which involved underlying hepatobiliary diseases, representing an important risk factor. In 12 of the 28 cases, the infections involved the hepatobiliary system; with a tendency towards an Asian origin. In our case series of nine patients, Shewanella haliotis was isolated in five patients. The majority of our patients lived in coastal areas, consumed seafood regularly and developed bacteremia during the summer season.

Conclusion: It is recommended that the possibility for Shewanella infection be considered in patients with bacteremia and also underlying hepatobiliary diseases, particularly if patients present with hepatobiliary infections, a history of seafood, or development of the disease during the summer.
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http://dx.doi.org/10.2169/internalmedicine.52.8152DOI Listing
August 2013

Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia.

Mol Cell Endocrinol 2013 Mar 29;367(1-2):50-6. Epub 2012 Dec 29.

Division of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Hyperglycemia is common after acute stroke. In the acute phase of stroke (within 24h), rats with permanent cerebral ischemia developed higher fasting blood glucose and insulin levels in association with up-regulation of hepatic gluconeogenic gene expression, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase. In addition, hepatic gluconeogenesis-associated positive regulators, such as FoxO1, CAATT/enhancer-binding proteins (C/EBPs), and cAMP responsive element-binding protein (CREB), were up-regulated. For insulin signaling transduction, phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1) at the tyrosine residue, Akt, and AMP-activated protein kinase (AMPK), were attenuated in the liver, while negative regulators of insulin action, including phosphorylation of p38, c-Jun N-terminal kinase (JNK), and insulin receptor substrate-1 (IRS1) at the serine residue, were increased. In addition, the brains of rats with stroke exhibited a reduction in phosphorylation of IRS1 at the tyrosine residue and Akt. Circulating cortisol, glucagon, C-reactive protein (CRP), monocyte chemoattractant protein 1 (MCP-1), and resistin levels were elevated, but adiponectin was reduced. Our data suggest that cerebral ischemic insults might modify intracellular and extracellular environments, favoring hepatic gluconeogenesis and the consequences of hyperglycemia.
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http://dx.doi.org/10.1016/j.mce.2012.12.016DOI Listing
March 2013

Evidence of intracellular stages in Trypanosoma (Megatrypanum) theileri in non-phagocytic mammalian cells.

Vet Parasitol 2013 Jan 4;191(3-4):228-39. Epub 2012 Sep 4.

Department of Medical Education and Research, Taichung Veterans General Hospital, 160, Sec. 3, Taichung 40705, Taiwan.

Trypanosoma (subgenus Megatrypanum) theileri was first identified over one hundred years ago, and is a widespread parasite in cattle. Its life cycle within the mammalian host has rarely been reported. Whether there is an intracellular stage in tissues is unknown and such a stage has not been demonstrated experimentally. Intriguingly, using Giemsa staining with light microscopy and transmission electron microscopy examination, we found that the parasite was able not only to attach to cells but also to invade several phagocytic and non-phagocytic mammalian cells. Based on these findings, we conducted further investigations using a special antibody in immunofluorescence confocal images. Moreover, we examined a series of possible events of cell invasion in T. theileri. The results revealed that GM1, a marker of membrane rafts, was implicated in the mechanism of entry by this parasite. After incubation with tissue culture trypomastigotes, the gelatinolytic activity was significantly increased and accumulated at the attachment sites. Using ultrastructural localization detection by CytoTracker live imaging and confocal immunofluorescence microscopy, we found that lysosome fusion and the autophagy pathway were engaged in invaginating processes. T. theileri amastigotes also invaded cells and were enclosed by the lysosomes. Furthermore, tissue-cultured trypomastigotes were found to be capable of triggering intracellular free Ca(2+) transients and TGF-β-signaling. Our findings that intracellular amastigote stages exist in mammalian cells infected with T. theileri and that the invasion processes involved various host cell components and cell signalings were extremely surprising and warrant further investigation.
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http://dx.doi.org/10.1016/j.vetpar.2012.08.027DOI Listing
January 2013

Shewanella infection of snake bites: a twelve-year retrospective study.

Clinics (Sao Paulo) 2012 ;67(5):431-5

Taichung Veterans General Hospital, Department of Internal Medicine, Section of Infectious Diseases, Taichung, Taiwan.

Objective: Infections of snake bite wounds by Shewanella are rarely discussed in the medical literature. This study aims to characterize the presentation and management of Shewanella infections in snake bite wounds.

Method: We retrospectively investigated the microbiology, clinical features, and outcomes of patients with Shewanella infected snake bite wounds admitted to a tertiary medical center from January 1998 to December 2009.

Results: Ten patients with Shewanella-infected snake bite wounds were identified. All of the snake bites were caused by cobras. The majority of patients had moderate to severe local envenomation and polymicrobial infections. Shewanella isolates are susceptible to ampicillin-sulbactam, piperacillin-tazobactam, third-and fourth-generation cephalosporins, carbapenems, aminoglycosides, and quinolones but are resistant to penicillin and cefazolin. All of the patients examined had favorable outcomes.

Conclusion: It is recommended that Shewanella infection be considered in snake bite patients, especially when patients present with moderate to severe local envenomation.
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http://dx.doi.org/10.6061/clinics/2012(05)05DOI Listing
February 2013

Study of the endoparasitic fauna of commensal rats and shrews caught in traditional wet markets in Taichung City, Taiwan.

J Microbiol Immunol Infect 2013 Apr 18;46(2):85-8. Epub 2012 Apr 18.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.

Background: Rats live in close proximity to human populations. Feral rodents are known to transmit diseases and act as reservoir hosts to many zoonotic parasites that pose health risks to humans. The aim of this study is to investigate endoparasitic infections in commensal rats and shrews caught in traditional wet markets in Taichung City, Taiwan.

Methods: A total of 51 commensal wild rodents and shrews were caught in traditional wet markets in Taichung City, including 32 Rattus norvegicus, 11 R. rattus, and eight Suncus murinus. All tissues, organs, and intestinal contents were carefully examined after euthanasia for the detection of parasites.

Results: The overall prevalence of infection was 94.1%, and the infection rates in R. norvegicus, R. rattus, and S. murinus were 93.8%, 90.9%, and 100.0%, respectively. Four cestodes (Taenia taeniaeformis, Hymenolepis diminuta, H. nana, and Raillietina celebensis), seven nematodes (Angiostrongylus cantonensis, Capillaria hepatica, Heterakis spumosa, Nippostrongylus brasiliensis, Strongyloides ratti, Syphacia muris, and Trichosomoides crassicauda), and one protozoan (Sarcocystis spp.) were detected.

Conclusion: Our findings indicate that commensal rodents and shrews found in the traditional wet markets of Taichung City are hosts to various zoonotic parasites and, therefore, pose a serious health risk to humans and domestic animals in Taiwan.
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http://dx.doi.org/10.1016/j.jmii.2012.01.012DOI Listing
April 2013

Phylogenetic relationships of rat lungworm, Angiostrongylus cantonensis, isolated from different geographical regions revealed widespread multiple lineages.

Parasitol Int 2012 Sep 25;61(3):431-6. Epub 2012 Feb 25.

Section of Environmental Parasitology, Graduate School of Tokyo Medical and Dental University, Yushima, Tokyo 113-8519, Japan.

We conducted a pilot survey of genetic variation of A. cantonensis using small subunit (SSU) ribosomal (r) RNA and mitochondrial cytochrome c oxidase subunit I (coxI) gene sequences. Two distinct SSU genotypes (G1 and G2) were identified among 17 individual A. cantonensis worms from 17 different geographical localities in Japan, Mainland China, Taiwan, and Thailand. The partial coxI sequences were determined for 83 worms from 18 different geographical localities from Japan, Mainland China, Taiwan, and Thailand. Phylogenetic analysis showed eight distinct coxI haplotypes (ac1 to ac8). In 16 out of 18 localities, only a single coxI haplotype was found. However, in two localities, two coxI haplotypes coexisted. The common haplotypes found were: haplotype ac1 (Tokyo, Chiba, Kanagawa, Amamioshima Island, and Taichung), haplotype ac2 (Ishikawa, Shenzhen, and Lianjiang), haplotype ac5 (the Okinawa and the Ogasawara Islands), and haplotype ac7 (Miyagi, Aichi, and Kanagawa). Each of these regions is separated from the others by high mountain ranges or oceans. In addition, the lower genetic variation and particular geographical distribution of A. cantonensis in each location could indicate a founder effect, which may have resulted from multiple independent origins, and suggests that haplotypes migrated from endemic areas via human-related transportation.
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http://dx.doi.org/10.1016/j.parint.2012.02.005DOI Listing
September 2012

Effects of Shugan-Huayu powder, a traditional Chinese medicine, on hepatic fibrosis in rat model.

Chin J Physiol 2010 Aug;53(4):223-33

Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan, Republic of China.

Shugan-Huayu powder (SHP) has been administered to outpatients with chronic liver disease without clear anti-fibrosis mechanism. To investigate the anti-fibrotic effects of SHP on liver fibrosis in a rat model and in hepatic stellate cells (HSCs) in vitro, rats were gavaged with CCl4 at 1.0 g/kg body weight twice a week for 8 weeks to induce liver fibrosis and the rats were randomly assigned to one of the three groups: -CCl4 alone, low-dose SHP and high-dose SHP. SHP was given by gavages 5 times a week for 8 weeks. Serum, livers and HSCs were assayed for serology, pathology, western blot, zymography and quantitative RT-PCR. Hepatic function improved as decreased serum aspartate aminotransferase and alanine aminotransferase, and collagen deposition and active HSCs were significantly reduced in CCl4-induced liver by SHP treatment. The expression of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta1 (TGF-beta1) mRNA in fibrotic liver showed significant downregulation after SHP treatment. In vitro, inhibition of alpha-smooth muscle actin (alpha-SMA) expression and MMP-2 secretion of active HSCs were also noticed by SHP treatment. SHP has an antifibrotic effect on CCl4-induced liver fibrosis in rats. Anti-fibrotic mechanisms were probably inhibiting activation of HSCs and decreased expression of MMP-2 and TGF-beta1.
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http://dx.doi.org/10.4077/cjp.2010.amk050DOI Listing
August 2010

Serological survey for antibodies to Encephalitozoon cuniculi in rabbits in Taiwan.

Vet Parasitol 2011 Dec 24;183(1-2):68-71. Epub 2011 Jun 24.

Department of Veterinary Medicine, College of Agriculture, National Chiayi University, 300 Syuefu Road, Chiayi City, Taiwan.

Encephalitozoon cuniculi (E. cuniculi) is a microsporidian parasite commonly found in rabbits that can infect humans, causing encephalitozoonosis. Our laboratory recently confirmed the first case of encephalitozoonosis in a rabbit in Taiwan; the prevalence of encephalitozoonosis is not well documented, even when many clinics suspect pet rabbits as being infected. This study surveys the seropositivity of E. cuniculi using carbon immunoassay (CIA) and enzyme-linked immunosorbent assay (ELISA). Serological examination of 171 rabbits using CIA and ELISA showed that 63.2% (108/171) and 67.8% (116/171) were seropositive against E. cuniculi, respectively. Thirteen of the 14 rabbits (92.9%) with neurological symptoms were seropositive. Except for gender, health status and location had a significant effect on E. cuniculi seropositivity (p<0.05). Adult rabbits aged older than 4 months exhibited significantly higher seropositivity for E. cuniculi than young rabbits (p<0.05). In conclusion, this study shows that E. cuniculi is present and widespread among healthy rabbits in Taiwan. Therefore, the fields of veterinary and human medicine in Taiwan should be aware of this zoonotic issue and the resulting public health concern of encephalitozoonosis.
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http://dx.doi.org/10.1016/j.vetpar.2011.06.011DOI Listing
December 2011
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