• Title/Summary/Keyword: Aberrant

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Epidemiological investigation of equine hindlimb ataxia with Setaria digitata in South Korea

  • Hwang, Hyeshin;Ro, Younghye;Lee, Hyunkyoung;Kim, Jihyeon;Lee, Kyunghyun;Choi, Eun-Jin;Bae, You-Chan;So, ByungJae;Kwon, Dohoon;Kim, Ho;Lee, Inhyung
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.75.1-75.7
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    • 2022
  • Background: Since 2013, the number of requests for diagnosis for horses based on neurological symptoms has increased rapidly in South Korea. The affected horses have commonly exhibited symptoms of acute seasonal hindlimb ataxia. A previous study from 2015-2016 identified Setaria digitata as the causative agent. Objectives: This study is an epidemiological investigation to find out risk factors related to the rapid increase in hindlimb ataxia of horses due to aberrant parasites in South Korea. Methods: An epidemiological investigation was conducted on 155 cohabiting horses in 41 horse ranches where the disease occurred. The surrounding environment was investigated at the disease-causing horse ranches (n = 41) and 20, randomly selected, non-infected ranches. Results: Hindlimb ataxia was confirmed in nine cohabiting horses; this was presumed to be caused by ectopic parasitism. Environments that mosquitoes inhabit, such as paddy fields within 2 km and less than 0.5 km from a river, had the greatest association with disease occurrence. Conclusions: Most horse ranches in South Korea are situated in favorable environments for mosquitoes. Moreover, the number of mosquitoes in the country has increased since 2013 due to climate change. Additional research is required; however, these data show that it is necessary to establish guidelines for the use of anthelmintic agents based on local factors in South Korea and disinfection of the environment to prevent disease outbreaks.

Prevention, diagnosis, and treatment of opioid use disorder under the supervision of opioid stewardship programs: it's time to act now

  • Kim, Eun-Ji;Hwang, Eun-Jung;Yoo, Yeong-Min;Kim, Kyung-Hoon
    • The Korean Journal of Pain
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    • v.35 no.4
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    • pp.361-382
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    • 2022
  • The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as α2 agonists, β-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD.

Alterations in Functions of Cognitive Emotion Regulation and Related Brain Regions in Maltreatment Victims (아동기 학대 경험이 인지적 정서조절 능력 및 관련 뇌영역 기능에 미치는 영향)

  • Kim, Seungho;Lee, Sang Won;Chang, Yongmin;Lee, Seung Jae
    • Korean Journal of Biological Psychiatry
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    • v.29 no.1
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    • pp.15-21
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    • 2022
  • Objectives Maltreatment experiences can alter brain function related to emotion regulation, such as cognitive reappraisal. While dysregulation of emotion is an important risk factor to mental health problems in maltreated people, studies reported alterations in brain networks related to cognitive reappraisal are still lacking. Methods Twenty-seven healthy subjects were recruited in this study. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form and the Cognitive Emotion Regulation Questionnaire, respectively. Twelve subjects reported one or more moderate maltreatment experiences. Subjects were re-exposed to pictures after the cognitive reappraisal task using the International Affective Picture System during fMRI scan. Results The maltreatment group reported more negative feelings on negative pictures which tried cognitive reappraisal than the no-maltreatment group (p < 0.05). Activities in the right superior marginal gyrus and right middle temporal gyrus were higher in the maltreatment group (uncorrected p < 0.001, cluster size > 20). Conclusions We found that paradoxical activities in semantic networks were shown in the victims of maltreatment. Further study might be needed to clarify these aberrant functions in semantic networks related to maltreatment experiences.

Clinical Application of a Newly Developed Basket Device for Interventional Heartworm Extraction in Three Dogs

  • Lee, Yooyoung;Kim, Hyesung;Yoon, Kwangyong;Park, Jihyeon;Oh, Younna;Oh, Miju;Ban, Jiyoung;Lee, Minju;Kim, Hakhyun;Kang, Byeong-Teck;Chang, Dongwoo
    • Journal of Veterinary Clinics
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    • v.39 no.4
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    • pp.177-184
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    • 2022
  • Caval syndrome is a severe complication of canine heartworm disease in which affected dogs present with various clinical signs that are often life-threatening. In cases of severe infection, adulticidal treatment has numerous complications as a result of a marked immune response against dead worms. Therefore, several surgical and non-surgical methods, including interventional extraction, have been applied in veterinary medicine. Despite the usefulness and efficiency of conventional retrieval devices, a few associated limitations must be addressed to reduce their risks and increase their applicability. Herein, we introduced a case of treating three dogs with caval syndrome by applying a newly developed heartworm basket device. The dogs were diagnosed with heartworm disease by heartworm antigen testing and direct smear. Imaging findings revealed remarkable remodeling of the right heart and pulmonary vessels and the presence of heartworms in the right heart. Additionally, heartworms were confirmed in the distal part of the abdominal aorta and femoral arteries in one dog, indicating aberrant systemic migration of the worms. Under general anesthesia, the heartworm basket device was introduced into the right heart via femoral venotomy and arteriotomy in one dog and jugular venotomy in the other two dogs. Although the number of cases in this study was small, the basket device was successful in gradual and cautious extraction of the heartworms in all three dogs. They exhibited good prognosis of clinical symptoms as indicated by imaging analyses.

Prevention of UV-induced Skin Damage by Activation of Tumor Suppressor Genes p53 and $p14^{ARF}$

  • Petersen, R.;John, S.;Lueder, M.;Borchert, S.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.338-351
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    • 2003
  • UV radiation is the most dangerous stress factor among permanent environmental impacts on human skin. Consequences of UV exposure are aberrant tissue architecture, alterations in skin cells including functional changes. Nowadays new kinds of outdoor leisure-time activities and changing environmental conditions make the question of sun protection more important than ever. It is necessary to recognize that self-confident consumers do not consider to change their way of life, they demand modern solutions on the basis of new scientific developments. In the past one fundamental principle of cosmetics was the use of physical and organic filter systems against damaging UV-rays. Today new research results demonstrate that natural protecting cell mechanisms can be activated. Suitable biological actives strongly support the protection function not from the surface but from the inside of the cell. A soy seed preparation (SSP) was proven to stimulate natural skin protective functions. The major functions are an increased energy level and the prevention of DNA damage. These functions can I be defined as biological UV protection. The tumor suppressor protein p53 plays a key role in the regulation of DNA repair. p53 must be transferred into the phosphorylated form to work as transcription factor for genes which are regulating the cell cycle or organizing DNA repair. A pretreatment with SSP increases the phosphorylation rate of p53 of chronically UV-irradiated human keratinocytes significantly. According to the same test procedure SSP induces a dramatic increase in the expression of the tumor suppressor protein p14$^{ARF}$ that is supporting the p53 activity by blocking the antagonist of p53, the oncoprotein Mdm2. Mdm2, a ubiquitin E3-ligase, downregulates p53 and at the same time it prevents phosphorylation of p53. The positive influence of the tumor suppressor proteins explains the stimulation of DNA repair and prevention of sunburn cell formation by SSP, which was proven in cell culture experiments. In vivo the increased skin tolerance against UV irradiation by SSP could be confirmed too. We have assumed, that an increased repair potential provides full cell functionality.y.

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Gene Expression Analyses of Mutant Flammulina velutipes (Enokitake Mushroom) with Clogging Phenomenon

  • Ju-Ri Woo;Doo-Ho Choi;Muhammed Taofiq Hamza;Kyung-Oh Doh;Chang-Yoon Lee;Yeon-Sik Choo;Sangman Lee;Jong-Guk Kim;Heeyoun Bunch;Young-Bae Seu
    • Mycobiology
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    • v.50 no.5
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    • pp.366-373
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    • 2022
  • Regulation of proper gene expression is important for cellular and organismal survival, maintenance, and growth. Abnormal gene expression, even for a single critical gene, can thwart cellular integrity and normal physiology to cause diseases, aging, and death. Therefore, gene expression profiling serves as a powerful tool to understand the pathology of diseases and to cure them. In this study, the difference in gene expression in Flammulina velutipes was compared between the wild type (WT) mushroom and the mutant one with clogging phenomenon. Differentially expressed transcripts were screened to identify the candidate genes responsible for the mutant phenotype using the DNA microarray analysis. A total of 88 genes including 60 upregulated and 28 downregulated genes were validated using the real-time quantitative PCR analysis. In addition, proteomic differences between the WT and mutant mushroom were analyzed using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Interestingly, the genes identified by these genomic and proteomic analyses were involved in stress response, translation, and energy/sugar metabolism, including HSP70, elongation factor 2, and pyruvate kinase. Together, our data suggest that the aberrant expression of these genes attributes to the mutant clogging phenotype. We propose that these genes can be targeted to foster normal growth in F. velutipes.

Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis

  • Hyunsik Kim;Soo-Yeon Park;Soo Yeon Lee;Jae-Hwan Kwon;Seunghee Byun;Mi Jeong Kim;Sungryul Yu;Jung-Yoon Yoo;Ho-Geun Yoon
    • BMB Reports
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    • v.56 no.2
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    • pp.114-119
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    • 2023
  • Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson's Disease

  • Yujin Choi;Eugene Huh;Seungmin Lee;Jin Hee Kim;Myoung Gyu Park;Seung-Yong Seo;Sun Yeou Kim;Myung Sook Oh
    • Biomolecules & Therapeutics
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    • v.31 no.4
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    • pp.402-410
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    • 2023
  • Long-term administration of levodopa (L-DOPA) to patients with Parkinson's disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

The Effect of Treadmill Exercise on Tau Hyperphosphorylayion in an Aged Transgenic Mouse Model of Taupathies

  • Wang, Seong-Hwan;Kang, Eun-Bum;Kwon, In-Su;Koo, Jung-Hoon;Shin, Kwang-O;Jang, Yong-Chul;Um, Hyun-Sub;Oh, Yoo-Sung;Kim, Chul-Hyun;Cho, In-Ho;Cho, Joon-Yong
    • Korean Journal of Exercise Nutrition
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    • v.16 no.2
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    • pp.93-100
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    • 2012
  • Alzheimer's disease (AD) is the most common cause of dementia in adults. Microtubule associated protein tau is abnormally phosphorylated in AD and aggregates as paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). NFTs are the most common intraneuronal inclusion in the brains of patients with AD and have been implicated in mediating neuronal cell death and cognitive deficit. Aberrant phosphorylation of tau is an early pathological event in AD, but the underlying mechanisms are unclear. MAP kinases are a family of Serine/Threonine (Ser/Thr) kinases that involved hyper - phosphorylation of tau in AD. The purpose of this study was to investigate the effect of treadmill exercise on phosphorylation of tau level and activation of MAPKs including JNK, ERK, p38-MAPK. To address this, Tg mouse model of AD, Tg-NSE/hTau 23, which expresses human tau 23 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. Treadmill exercise in Tg group improved cognitive function compared with Tg-SED group in watermaze test. In addition, treadmill exercised Tg mice significantly reduced the activation of JNK54/46, p38-MAPK and tau (Ser404, Ser202, Thr231), and increased activation of ERK44/42 in cerebral cortex. These results suggest that treadmill exercise may provide a therapeutic potential to alleviate the tau pathology like AD.

Prospective Targets for Colon Cancer Prevention: from Basic Research, Epidemiology and Clinical Trial

  • Shingo Miyamoto;Masaru Terasaki;Rikako Ishigamori;Gen Fujii;Michihiro Mutoh
    • Journal of Digestive Cancer Research
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    • v.4 no.2
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    • pp.64-76
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    • 2016
  • The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

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