• Title/Summary/Keyword: Metabolic disorder

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Transdifferentiation of α-1,3-Galactosyltransferase Knock Out (GalT KO) Pig Derived Bone Marrow Mesenchymal Stromal Cells (BM-MSCs) into Pancreatic Cells by Transfection of hPDX1 (hPDX1 유전자의 삽입에 의한 직접 췌도세포 분화)

  • Ock, Sun A;Oh, Keon Bong;Hwang, Seongsoo;Kim, Youngim;Kwon, Dae-Jin;Im, Gi-Sun
    • Journal of Embryo Transfer
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    • v.30 no.3
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    • pp.249-255
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    • 2015
  • Diabetes mellitus, the most common metabolic disorder, is divided into two types: type 1 and type 2. The essential treatment of type 1 diabetes, caused by immune-mediated destruction of ${\beta}-cells$, is transplantation of the pancreas; however, this treatment is limited by issues such as the lack of donors for islet transplantation and immune rejection. As an alternative approach, stem cell therapy has been used as a new tool. The present study revealed that bone marrowderived mesenchymal stromal cells (BM-MSCs) could be transdifferentiated into pancreatic cells by the insertion of a key gene for embryonic development of the pancreas, the pancreatic and duodenal homeobox factor 1 (PDX1). To avoid immune rejection associated with xenotransplantation and to develop a new cell-based treatment, BM-MSCs from ${\alpha}$-1,3-galactosyltransferase knockout (GalT KO) pigs were used as the source of the cells. Transfection of the EGFP-hPDX1 gene into GalT KO pig-derived BM-MSCs was performed by electroporation. Cells were evaluated for hPDX1 expression by immunofluorescence and RT-PCR. Transdifferentiation into pancreatic cells was confirmed by morphological transformation, immunofluorescence, and endogenous pPDX1 gene expression. At 3~4 weeks after transduction, cell morphology changed from spindle-like shape to round shape, similar to that observed in cuboidal epithelium expressing EGFP. Results of RT-PCR confirmed the expression of both exogenous hPDX1 and endogenous pPDX1. Therefore, GalT KO pig-derived BM-MSCs transdifferentiated into pancreatic cells by transfection of hPDX1. The present results are indicative of the therapeutic potential of PDX1-expressing GalT KO pig-derived BM-MSCs in ${\beta}-cell$ replacement. This potential needs to be explored further by using in vivo studies to confirm these findings.

Effects of Cuscutae Semen Extract on Prevention of Osteoporosis in Ovariectomized Rats (토사자(兎絲子)가 난소적출(卵巢摘出)로 유도(誘導)된 흰쥐의 골다공증(骨多孔症)에 미치는 영향(影響))

  • Kim, Jong-Hyun;Kim, Ho-Seok;Jun, Jae-Yun;Jeong, Da-Won;Cho, Chang-Young;Sohn, Young-Joo;Jung, Hyuk-Sang
    • The Journal of Korean Obstetrics and Gynecology
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    • v.25 no.4
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    • pp.1-11
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    • 2012
  • Objectives: Osteoporosis, which occurs after menopause, is a kind of metabolic bone disorder. It develops when the bone mass begins to decrease radically, and its main symptoms are bone fracture and height-shortening. This thesis aims at what effects the Cuscutae Semen Extract(CSE) has on the prevention of osteoporosis in SD-rat that is caused by ovariectomy. Methods: The 24 female white rats, after removing their ovaries, were divided into the Normals, the Control group, and the CSE administrated group. For the next 8 weeks, distilled water to the normals and the control, and the CSE(45.9 mg/100 g) to the CSE administrated group were given in the mouths of them. After 8 weeks the rats were sacrificed. Weight, albumin, aspartate aminotransferase, alanine aminotransferase, total-cholesterol, triglyceride, phosphorus, calcium, tetraiodothyronine, estradiol, the weight of the femur, the amount of tibia ash, the area of trabecular bone, and the thickness of trabecular bone were measured. Results: The serum analysis shows that the calcium and phosphorous of the CSE administrated group significantly increased compared to that of the control group. Aspartate aminotransferase, alkalinephosphatase, total cholesterol, tetraiodothyronine of CSE group were decreased, but not so significant. Albumin, alanine aminotransferase, triglyceride and estradiol of the group showed the tendency to increase, but the significance wasn't admitted. Regarding the variation of bone, the femur weight and the ash content of tibia, CSE group was more increased than the control group but the significance wasn't admitted. The histological observation shows that the trabecular thickness was more increased than the control group, and trabecular area increased significantly compared to those of the control group. The number of osteoclast and osteoblast area of the CSE groups decreased significantly compared to those of the control group. Conclusions: From the result of the above study, CSE should be effective for the osteoporosis cure and precaution and deeper study through bedside and clinical demonstration is much needed from now on.

Inhibitory Effects of Illicium verum Hooker fil. Dichloromethane Fractions on Adipocyte Differentiation (팔각회향 dichloromethane 분획물에 의한 지방세포 분화 억제 효과)

  • Jeong, Hyun Young;Jeong, In Kyo;Kim, Nam Ju;Yun, Hee Jung;Park, Jung Ha;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.29 no.4
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    • pp.447-454
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    • 2019
  • Fat accumulation in adipocytes occurs through the process of adipogenesis in which preadipocytes differentiate into adipocytes. Obesity is a metabolic disorder caused by excessive accumulation of fat in the body, which increases the incidence of cardiovascular diseases, hypertension, type 2 diabetes, hyperlipidemia, and various cancers. Recently, inhibition of adipocyte differentiation was shown to be a potential antiobesity strategy. In this study, the inhibitory effect of dichloromethane fractions from Illicium verum Hooker fil. water extract on the differentiation of 3T3-L1 preadipocytes to adipocytes was investigated. Dichloromethane fractions from I. verum Hooker fil. significantly inhibited adipocyte differentiation when applied during the adipocyte differentiation process, as assessed by measuring fat accumulation using Oil-red O staining. In addition, dichloromethane fractions from I. verum Hooker fil. reduced important adipogenic transcription factors, such as CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and peroxisome proliferator activated receptor ${\gamma}$ ($PPAR{\gamma}$). The expression of FAS and LPL, which are terminal differentiation markers of mature adipocytes, was also reduced in the 3T3-L1 adipocytes treated with dichloromethane fractions from I. verum Hooker fil. In addition, the treatment significantly inhibited mitotic clonal expansion, which is essential for adipocyte differentiation, by arresting the G1 phase of the cell cycle. Taken together, these results suggest that dichloromethane fractions from I. verum Hooker fil. may be a natural material with antiobesity effects.

Ulmus macrocarpa Hance Reduces Cyclophosphamide-induced Toxicity in Mouse Liver (Cyclophosphamide가 유발한 간 조직변화에 대한 느릅나무 열수추출물의 완화 효과)

  • Kim, Deok Won;Chung, Kyung Tae
    • Journal of Life Science
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    • v.31 no.2
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    • pp.223-228
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    • 2021
  • Cyclophosphamide (CP) is widely used in cancer and lymphoma treatments and as an immunosuppressant drug. CP is a DNA alkylating agent that metabolizes into 4-hydrocyclophosphamide (4H-CYP) and aldophosphamide in hepatocytes. However, its metabolites cause DNA synthesis disorder, leading to apoptosis and toxic side effects. The development of technology to minimize this side effect is essential to improve CP's clinical application. Various bioactive compounds have been reported to have anti-cancer and antioxidant functions and preventive or therapeutic roles in metabolic diseases. Many researchers have attempted to minimize the side effects and improve the efficacy of these drugs together with the use of bioactive compounds. Ulmus macrocarpa Hance has been used for the treatment of edema, mastitis, stomach pain, tumors, cystitis, and other inflammatory diseases. The aim of this study was to investigate at the histological level the protective function of U. macrocarpa Hance against CP's side effects and any potential toxic effect of U. macrocarpa Hance in the liver and kidney. Water extracts of U. macrocarpa Hance reduced CP-induced toxicity and did not induce any histological damage in the liver and kidney. Therefore, U. macrocarpa Hance would be applicable in the pharmaceutical industry.

Recent Studies on Anorexia and Tissue Wasting Induced by Cancer Cachexia (암 악액질의 주요 병인 기전 및 최근 연구 동향)

  • Yeom, Eunbyul
    • Journal of Life Science
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    • v.32 no.3
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    • pp.263-269
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    • 2022
  • Cancer cachexia-anorexia is a multi-organ metabolic syndrome characterized by anorexia and weight loss. Generally, such symptoms are a serious problem in cancer patients, adversely affecting chemotherapy success and survival rate. Cachexia has been reported to accompany up to 80% of gastrointestinal cancers, such as pancreatic, lung, and colon cancer, though it is relatively rare in lymphoma or breast cancer patients. It is also known that cancer-induced anorexia occurs independently of chemotherapy, although decreased appetite due to chemotherapy is well reported. In terms of pathoflammatory cytokines that are excessively increased by tumor tissues. Since the mechanism of cancer cachexia is not yet fully understood, there are currently no therapeutic agents or diagnostic markers to treat it. A recently published study identified a substance secreted from cancer cells that induces cancer anorexia, and the molecular mechanism causing the eating disorder was discovered. An increase in the expression of this substance has been shown to be statistically correlated with the symptoms of cachexia in cancer patients, and it is therefore expected to be applicable in the diagnosis and development of therapeutic agents for cancer cachexia. This review article aims to provide an overview of the key molecular mechanisms of the anorexia and tissue wasting caused by cancer cachexia.

Effects of Plantaginis Semen & Poria (CJB) Water Extract on Histomorphometrical Aspects and Histopathological Changes in High Fat Diet-induced Obese Rats (차전자·복령의 복합 물추출물(CJB)이 고지방사료로 유도된 비만 생쥐의 조직형태 및 조직병리학적 변화에 미치는 영향)

  • Hwang, Jeong Soo;Suk, Jang Mi;Choi, Hye min;Shin, Insoon;Hwang, Su Jung;Park, Ji Young;Kim, Sung Ok;Seo, Bu Il;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.91-96
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    • 2013
  • Objectives : Obesity is a chronic metabolic disease caused by disorder of energy balance and lipid metabolism. This study was conducted by histopathology and histomorphometry to investigate the anti-obesity effects of mixed water extract of Plantaginis Semen & Poria (CJB) on liver, epididymal fat pads and pancreas zymogen granules in obese rats induced with high fat diet. Method : Male Sprague-Dawley rats to be divided four groups were fed into four different treatments: normal (NOR) diet, high-fat (HF) diet, HF diet+CJB (100 mg/kg and 300 mg/kg, P.O.) for 8 weeks. The weekly body weights were measured in four experimental groups, respectively. Also histopathological and histomorphometrical changes of liver, epididymal fat pads and pancreas zymogen granules were observed in normal control and obese rats, respectively. Results : Adminstration of CJB significantly reduced body weights compared to those of HF group for experimental period. After 8 weeks, liver weights in the CJB groups were lower than those of HF group. In addition, HF diet related steatohepatitis, adipocyte hypertrophy, exocrine disturbances (decreases of pancreatic zymogen granules) were also dose-dependently inhibited by treatment of test material, CJB 100 and CJB 300 as compared with HF group, respectively. Conclusion : Based on the results, it is considered that CJB will be showed hepatoprotective and anti-obese effects, may be directly and/or indirectly mediated by pancreatic zymogen granules because they dose-dependently inhibited steatohepatitis, hypertrophy of adipocytes and decreases of pancreatic zymogen granules induced by HF diet supply, respectively.

COVID-19 in a 16-Year-Old Adolescent With Mucopolysaccharidosis Type II: Case Report and Review of Literature

  • Park, So Yun;Kim, Heung Sik;Chu, Mi Ae;Chung, Myeong-Hee;Kang, Seokjin
    • Pediatric Infection and Vaccine
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    • v.29 no.2
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    • pp.70-76
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    • 2022
  • Coronavirus disease 2019 (COVID-19) in patients with underlying diseases, is associated with high infection and mortality rates, which may result in acute respiratory distress syndrome and death. Mucopolysaccharidosis (MPS) type II is a progressive metabolic disorder that stems from cellular accumulation of the glycosaminoglycans, heparan, and dermatan sulfate. Upper and lower airway obstruction and restrictive pulmonary diseases are common complaints of patients with MPS, and respiratory infections of bacterial or viral origin could result in fatal outcomes. We report a case of COVID-19 in a 16-year-old adolescent with MPS type II, who had been treated with idursulfase since 5 years of age. Prior to infection, the patient's clinical history included developmental delays, abdominal distension, snoring, and facial dysmorphism. His primary complaints at the time of admission included rhinorrhea, cough, and sputum without fever or increased oxygen demand. His heart rate, respiratory rate, and oxygen saturation were within the normal biological reference intervals, and chest radiography revealed no signs of pneumonia. Consequently, supportive therapy and quarantine were recommended. The patient experienced an uneventful course of COVID-19 despite underlying MPS type II, which may be the result of an unfavorable host cell environment and changes in expression patterns of proteins involved in interactions with viral proteins. Moreover, elevated serum heparan sulfate in patients with MPS may compete with cell surface heparan sulfate, which is essential for successful interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the host cell surface, thereby protecting against intracellular penetration by SARS-CoV-2.

The Effect of Breathing Meditation Qigong Therapy on the Recovery of Olfactory Disorders and Voice Handicap Index in Parkinson's Disease Patients (호흡명상기공테라피가 파킨슨병 환자의 후각 및 음성 기능장애 개선에 미치는 효과)

  • So Jung An;Hun Mo Ahn
    • Journal of Korean Medical Ki-Gong Academy
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    • v.23 no.1
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    • pp.10-29
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    • 2024
  • Objective : The purpose of this study is to determine whether An's breathing meditation qigong therapy (ABMQT) delivers bioenergy to the frontal lobe, prefrontal lobe, the olfactory tract in the mesolimbic pathway, olfactory bulb, CV22, CV21, olfactory area and vocal-related areas in Parkinson's disease (PD) patients to help improve olfactory disorders (anosmia) and vocal functions. Methods : The subjects of this study were 4 patients with idiopathic PD (3 males/1 female, 65.0±NA/68.7±10.2 years old). ABMQT was applied once a week, 120 minutes per session for 12 weeks in a non-invasive and noncontact manner, and the test before and after ABMQT application included olfactory impairment test the Korean version of Sniffin' stick test (KVSS), voice acoustic test, aerodynamic test, vocal handicap index (VHI-30), and auditory perception scale test tools. The results before and after the experiment were analyzed assuming a normal distribution, and a chi-square test was performed using a continuity correction, and the significance level was set to p<0.05. And the medical diagnosis and findings of the examiner (doctor in charge) before and after the experiment were described. Results : KVSS was significant as 0.2±0.5 and 9.0±0.0 before and after the experiment. There was no significant difference between the voice acoustic test FO and Jitter, the vocal aerodynamic test MPT, SP, AE, the vocal disorder index test, and the auditory perception test. However, the medical diagnosis findings of four study subjects showed that olfactory disorders, voice disorders, and laryngeal function were improved before and after the application of ABMQT. Conclusions : The breathing meditation qigong program showed significant effects on improving the olfactory disorders (anosmia) and speech function of each study subject. However, to produce meaningful results, it is thought that experiments involving a larger number of research participants are necessary, and additional blood and FMRI tests are conducted to verify metabolic activities and the olfactory neuron signal transmission system.

Molecular Genetic Analysis in Dystroglycanopathy with the Fukuyama Congenital Muscular Dystrophy Phenotype (Fukuyama 선천성 근이영양증에서의 분자유전학적 분석)

  • Cha, Lily Myung-Jin;Shin, Jae Eun;Kim, Se Hoon;Lee, Min Jung;Lee, Chul Ho;Lee, Young-Mock
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.2
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    • pp.48-54
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    • 2017
  • Purpose: Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal-recessive disorder characterized by early-onset hypotonia associated with brain malformations in dystroglycanopathy. Although the wide spectrum of congenital muscular dystrophies causes difficulty in diagnosis, correlating the genotype with the clinical phenotype can help diagnose FCMD. Here, we evaluated the correlation of targeted molecular genetic analysis of FKTN gene mutation with the FCMD phenotype. Methods: This study was conducted retrospectively with 9 subjects. Inclusion criteria included clinical symptoms characterized by early-onset hypotonia with magnetic resonance imaging (MRI) featuring brain malformations. FKTN gene-alteration analysis was performed using various FKTN gene-analysis methods, including sequencing. Results: Among the 9 subjects studied, 4 (44.4%) were male and 5 (55.6%) were female. The median age of onset of the first symptom was 3.1 months. The first symptom was a delayed milestone in 6 cases (66.7%). All 9 subjects (100%) presented with early-onset hypotonia and global delayed development. All subjects presented with cortical malformation in their brain MRIs. Of the 9 subjects, 6 subjects had previously undergone muscle biopsy and 4 cases (4/6; 66.7%) showed dystrophic or myopathic features. Pathogenic mutations causing FCMD were identified in 3 cases. Conclusions: In this study, all 3 subjects with FKTN mutations showed important MRI findings (pachygyria and cerebellar dysplasia). These data suggest that patients with characteristic phenotypes who show pachygyria and cerebellar abnormalities in brain MRIs may have a high probability of being diagnosed with FCMD.

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Improved Acroparesthesia During Enzyme Replacement Therapy in a Patient Lately Diagnosed with Fabry Disease (진단이 지연된 Fabry 병 환자에서 효소대체요법을 통한 사지 말단 동통의 호전을 보인 1례)

  • Yang, Aram;Kim, Jinsup;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.3
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    • pp.92-95
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    • 2017
  • Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an ${\alpha}$-galactosidase A (GLA, MIM 300644) enzyme deficiency due to pathogenic variants in the ${\alpha}$-galactosidase A gene (GLA). The disease leads to accumulation of globotriaosylceramide (Gb3) and related glycophospholipids affecting nearly all major organ systems, with the primary sites damaged by Gb3 including renal glomeruli, myocardium, neurons of the dorsal ganglion and autonomic nervous system, and vascular endothelial and smooth muscle. Progressive deposition in these organ systems present with various clinical manifestations including acroparesthesia, renal failure and heart failure. Here, we report a Chinese male diagnosed with Fabry disease in his late $4^{th}$ decades showing improvement of acroparesthesia during enzyme replacement therapy (ERT). A 48-year-old Chinese man who presented with chronic recurrent severe burning pain in his fingers and toes since the age of 10, with worse involvement of the former visited to our clinic for further evaluation. His medical history included a transient ischemic attack aged 40 and diagnosed with stage 4-5 chronic kidney disease aged 47. In the family history, the patient's brother was found to be have Fabry disease 1 month before his visit. Except for his brother, all other members of the family are healthy. Based on his medical history and family history, he was strongly suspicious for Fabry disease. He was found to have a galactose-alpha-1,3-galactose level 4.96 (Reference range, 42.5-67.9) suggestive of Fabry disease. The followed sequencing of GLA coding region in our patient revealed hemizyosity for the mutation c.988C>T (Q330X) in Exon 7. Since ERT start, he showed significant improvement in his symptoms of burning sensation of fingers and toes. On the contrary, due to deteriorating kidney function even with ERT, he is considered for kidney transplantation. Despite of diagnostic delay until late 4th decades, ERT showed a potential improvement of acroparesthesia in our patient. However, late start of ERT can lead to poor outcome in multiorgan function. Therefore, early diagnosis with high index of suspicion followed by continuous ERT with regular monitoring have an impact on quality of life in Fabry disease.

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