• 제목/요약/키워드: Acid-related disorders

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An Essential Role of the N-Terminal Region of ACSL1 in Linking Free Fatty Acids to Mitochondrial β-Oxidation in C2C12 Myotubes

  • Nan, Jinyan;Lee, Ji Seon;Lee, Seung-Ah;Lee, Dong-Sup;Park, Kyong Soo;Chung, Sung Soo
    • Molecules and Cells
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    • 제44권9호
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    • pp.637-646
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    • 2021
  • Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy

  • Naseer, Muhammad Imran;Alwasiyah, Mohammad Khalid;Abdulkareem, Angham Abdulrahman;Bajammal, Rayan Abdullah;Trujillo, Carlos;Abu-Elmagd, Muhammad;Jafri, Mohammad Alam;Chaudhary, Adeel G.;Al-Qahtani, Mohammad H.
    • Genes and Genomics
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    • 제40권11호
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    • pp.1149-1155
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    • 2018
  • Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.

Cloning and Characterization of Bovine Titin-cap (TCAP) Gene

  • Yu, S.L.;Chung, H.J.;Jung, K.C.;Sang, B.C.;Yoon, D.H.;Lee, S.H.;Kata, S.R.;Womack, J.E.;Lee, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • 제17권10호
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    • pp.1344-1349
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    • 2004
  • Titin-cap (TCAP), one of the abundant transcripts in skeletal muscles, was nvestigated in this study in cattle because of its role in regulating the proliferation and differentiation of myoblasts by interacting with the myostatin gene. From the 5, and 3, RACE experiments, full-length TCAP coding sequence was identified, comprising 166 amino acids. The amino acid comparison showed high sequence similarities with previously identified human (95.8%) and mouse (95.2%) TCAP genes. The TCAP expression, addressed by northern blot, is limited in muscle tissues as indicated by Valle et al. (1997). The radiation hybrid analysis localized the gene on BTA19, where the comparative human and porcine counterparts are on HSA17 and SSC12. A few muscle-related genetic disorders were mapped on HSA17 and some growth-related QTLs were identified on SSC12. The bovine TCAP gene found in this study opens up new possibilities for the investigation of muscle-related genetic diseases as well as meat yield traits in cattle.

육미지황탕가미방(六味地黃湯加味方)이 C57BL/6JHam-ob/ob mice의 비만(肥滿) 및 제2형 당뇨병(糖尿病)에 미치는 영향(影響) (Antiobese and Antidiabetic Effects of Yookmijihwang-tang-gamibang, a Traditional Polyherbal Formula on the Obese and Type II Diabetic C57BL/6JHam-ob/ob Mice)

  • 김태우;강석봉
    • 대한한의학방제학회지
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    • 제21권2호
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    • pp.110-120
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    • 2013
  • Objectives : The object of this study was to observe the pharmacological effects of Yookmijihwang-tang-gamibang (Liuweidihuang-tang-jiaweifang, YGB) consisted of 17 types of herbs has been traditionally used in Korean medicine for treating various disorders in clinics, aqueous extracts on the genetically obese and type II diabetic C57BL/6JHam-ob/ob(ob/ob) mice. Methods :Three different dosages of YGB were orally administered, once a day for 28 days to ob/ob mice with ob/ob control and C57BL/6JJms normoglycemic intact mice. Four weeks after treatments of YGB: the changes on the body weight, food consumption, blood glucose levels, leptin and adiponectin contents were observed for monitoring the antiobese and antidiabetic effects of YGB. The effects were compared to those of CLA(conjugated linoleic acid) which improve type II diabetes and inhibit related obesity. Results : After end of 28 days of continuous treatments, ob/ob control showed increases of adipocyte hypertrophy, vasodilated atrophic glomerulus which were detected with marked hyperplasia of pancreatic islets, insulin and glucagon producing cells. These obese and related type II diabetes induced in ob/ob mice were markedly and significantly inhibited by 28 days of continuous treatment of three dosages of YGB. The YGB 50mg/kg showed similar favorable effects on the diabetes and related diabetic complications as compared with CLA 750mg/kg in ob/ob mice of the present study. Conclusions : The results obtained in this study suggest that over 25mg/kg of YGB extracts favorably retarded the obese and type II diabetes in genetically obese and type II diabetic ob/ob mice.

The Korean Traditional Anti-obesity drug Gyeongshingangjeehwan Stimulates $AMPK{\alpha}$ Activation in Skeletal Muscle of OLETF Rats

  • Shin, Soon-Shik;Yoon, Mi-Chung
    • 대한의생명과학회지
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    • 제17권4호
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    • pp.273-281
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    • 2011
  • Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) inhibits obesity and insulin resistance in obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We investigated whether GGEx may affect AMP-activated protein kinase ${\alpha}$ ($AMPK{\alpha}$) since $AMPK{\alpha}$ activation is known to stimulate fatty acid oxidation in skeletal muscle of obese rodents. After OLETF rats were treated with GGEx, we studied the effects of GGEx on $AMPK{\alpha}$ and acetyl-CoA carboxylase (ACC) phosphorylation, and the expression of $AMPK{\alpha}$, $PPAR{\alpha}$, and $PPAR{\alpha}$ target genes. The effects of GGEx on mRNA expression of the above genes were also measured in C2C12 skeletal muscle cells. Administration of GGEx to OLETF rats for 8 weeks increased phosphorylation of $AMPK{\alpha}$ and ACC in skeletal muscle. GGEx also elevated skeletal muscle mRNA levels of $AMPK{\alpha}1$ and $AMPK{\alpha}2$ as well as $PPAR{\alpha}$ and its target genes. Consistent with the in vivo data, similar activation of genes was observed in GGEx-treated C2C12 cells. These results suggest that GGEx stimulates skeletal muscle $AMPK{\alpha}$ and $PPAR{\alpha}$ activation, leading to alleviation of obesity and related disorders.

당뇨환자에서 비케톤성 고혈당에 동반하여 나타난 전신성 무도병 1예 (Generalized Chorea-Ballismus Associated with Nonketotic Hyperglycemia in Diabetes Mellitus -A Case Report-)

  • 신현란;김지훈;박미영
    • Journal of Yeungnam Medical Science
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    • 제19권2호
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    • pp.136-143
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    • 2002
  • 저자들은 고령의 여성 당뇨 환자에서 비케톤성 고혈당과 동반되어 나타난 전신성 무도병과 그 특징적인 방사선학적 소견을 보이는 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

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일차 배양한 흰쥐 대뇌피질세포의 흥분성 및 산화적 신경세포손상에 대한 소전재조환의 억제효과 (Inhibitory Effects of Xiaoshuan Zaizao Wan on Excitotoxic and Oxidative Neuronal Damage Induced in Primary Cultured Rat Cortical Cells)

  • 조정숙
    • 약학회지
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    • 제47권6호
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    • pp.369-375
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    • 2003
  • Xiaoshuan Zaizao Wan (XZW) has been used in China to improve hemiplegia, deviation of eye and mouth, and dysphasia due to cerebral thrombosis. To characterize pharmacological actions of XZW, we evaluated its effects on neuronal cell damage induced in primary cultured rat cortical cells by various oxidative insults, glutamate or N-methyl-D-aspartate (NMDA), and $\beta$-amyloid fragment ($A_{\beta(25-35)}$). XZW was found to inhibit the oxidative neuronal damage induced by $H_2O_2$, xanthine/xanthine oxidase, or $Fe^{2+}$/ascorbic acid. It also attenuated the excitotoxic damage induced by glutamate or NMDA. The NMDA-induced neurotoxicity was more effectively inhibited than the glutamate-induced toxicity. In addition, we found that XZW protected neurons against the $A_{\beta(25-35)}$-induced toxicity. Moreover; XZW exhibited dramatic inhibition of lipid peroxidation in rat brain homogenates and mild 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together; these results demonstrate that XZW exerts neuroprotective effects against oxidative, excitotoxic, or $A_{\beta(25-35)}$-induced neuronal damage. These findings may provide pharmacological basis for its clinical usage treating the sequelae caused by cerebral thrombosis. Furthermore, XZW may exert beneficial effects on Alzheimer's disease and other oxidative stress-related neurodegenerative disorders.

Treatment Outcomes of Venlafaxine and Duloxetine in Refractory Burning Mouth Syndrome Patients

  • Kim, Moon-Jong;Kho, Hong-Seop
    • Journal of Oral Medicine and Pain
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    • 제44권3호
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    • pp.83-91
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    • 2019
  • Purpose: Venlafaxine and duloxetine have been shown to be effective in the treatment of neuropathic pain disorders. However, knowledge about the efficacy of venlafaxine and duloxetine on burning mouth syndrome (BMS) is still insufficient. The purpose of this study was to investigate the efficacy of venlafaxine and duloxetine on refractory BMS patients. Methods: Twelve refractory BMS patients who were prescribed venlafaxine or duloxetine were included in this study. These patients did not respond to previous administration of clonazepam, alpha-lipoic acid, gabapentin, and nortriptyline. All participants were the primary type of BMS patients who had no local and systemic factors related to the oral burning sensation. The intensities of oral symptoms following venlafaxine or duloxetine administration were compared with those before administration and at baseline. Results: Venlafaxine and duloxetine were prescribed to four and nine patients, respectively. One patient was prescribed both medications in turn. Among them, only two patients showed improvement of oral symptoms without side effects. In the other ten patients, symptoms failed to improve. Six of them reported that the drug was ineffective, and four of them stopped taking the medications on their own due to intolerable side effects, such as insomnia, constipation, drowsiness, dizziness, and xerostomia. Conclusions: Venlafaxine and duloxetine may only relieve oral symptoms in a minority of refractory BMS patients. Further large-scale studies are needed to determine the potential clinical factors that could predict the efficacy of venlafaxine and duloxetine.

Preventive effects of sea cucumber (Apostichopus japonicus) ethanol extract on palmitate-induced vascular injury in vivo

  • Zhang, Chunying;Cha, Seon-Heui
    • Fisheries and Aquatic Sciences
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    • 제25권2호
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    • pp.90-100
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    • 2022
  • Cardiovascular diseases (CVDs) have posed serious public health problems, accounting for nearly 30% of mortality worldwide and their incidence is still increasing. Therefore, new treatment resources are necessary to prevent or manage the ever-increasing population of patients with CVDs. Sea cucumber is well known for its medical and health benefit effects, but it is not well known what/how effect it has on vascular disease. In the present study, we examined the protect effect of sea cucumber, Apostichopus japonicus 80% ethanol extract (AJE) on zebrafish embryo with the stimulation of free fatty acid, palmitate (PA). In vivo study showed that AJE can attenuate PA-induced toxicity through relieving the rapid heartbeat, increasing the survival rate and reducing the malformation in both wild type and Tg (fli1a:eGFP) transgenic zebrafish lines. Additionally, compare with PA treated embryos, the yolk sac area, body length, axial vascular segment (AVS) and intersegmental vessel (ISV) of the co-treatment group of AJE and PA were comparable to the control group. Moreover, AJE lowered the expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and inflammation-related genes induced by PA, and inhibited PA-induced vascular development disorders. Our data preliminarily verify that AJE could be a candidate resource for the prevention or therapy of CVDs.

Potential role of phytochemicals in brain plasticity: Focus on polyunsaturated fatty acids

  • Yook, Jang Soo;Lee, Minchul
    • 운동영양학회지
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    • 제24권1호
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    • pp.14-18
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    • 2020
  • [Purpose] Functional foods are thought to strongly influence the structure and function of the brain. Previous studies have reported that brain-boosting diets may enhance neuroprotective functions. Certain foods are particularly rich in nutrients like phytochemicals that are known to support brain plasticity; such foods are commonly referred to as brain foods. [Methods] In this review, we briefly explore the scientific evidence supporting the neuroprotective activity of a number of phytochemicals with a focus on phenols and polyunsaturated fatty acids such as flavonoid, olive oil, and omega-3 fatty acid. [Results] The aim of this study was to systematically examine the primary issues related to phytochemicals in the brain. These include (a) the brain-gut-microbiome axis; (b) the effects of phytochemicals on gut microbiome and their potential role in brain plasticity; (c) the role of polyunsaturated fatty acids in brain health; and (d) the effects of nutrition and exercise on brain function. [Conclusion] This review provides evidence supporting the view that phytochemicals from medicinal plants play a vital role in maintaining brain plasticity by influencing the brain-gut-microbiome axis. The consumption of brain foods may have neuroprotective effects, thus protecting against neurodegenerative disorders and promoting brain health.