• Title/Summary/Keyword: Human disease

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Recombinant Human HAPLN1 Mitigates Pulmonary Emphysema by Increasing TGF-β Receptor I and Sirtuins Levels in Human Alveolar Epithelial Cells

  • Yongwei Piao;So Yoon Yun;Zhicheng Fu;Ji Min Jang;Moon Jung Back;Ha Hyung Kim;Dae Kyong Kim
    • Molecules and Cells
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    • v.46 no.9
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    • pp.558-572
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    • 2023
  • Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity

  • Ji-Hye Jung;Se-Ran Yang;Woo Jin Kim;Chin Kook Rhee;Seok-Ho Hong
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.1
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    • pp.52-64
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    • 2024
  • Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

The Study of Throat Disease's Concept, Pathology and Medical treatment in Sasang Constitutional Medicine (사상의학(四象醫學)에서 인후질환(咽喉疾患)의 의미(意味)와 병리(病理) 및 치료(治療)에 대한 고찰(考察))

  • Ban, Duk-Jin;Park, Seong-Sik
    • Journal of Sasang Constitutional Medicine
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    • v.20 no.3
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    • pp.40-50
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    • 2008
  • 1. Objectives We analyze throat disease focused on Sasang constitutional medicine and find out throat disease's concept, pathology and medical treatment. 2. Methods We consider term, conceuption, symptoms, mechanism and medical treatment of throat disease in "Dongyisusebowon", "Dongyisusebowon Gabogubon", "Dongyisusebowon sasangchobongwon", "Dongyisasangshinpyun" and "Dongmuyoogo" 3. Results and conclusions 1) We find out throat disease's some concept that are refered variety in sasang constitutional medicine. 2) Throat disease's pathology are different according to sasang constitution. In Soeumin throat disease belong to taeeum syndrome and soeum syndrome, in Soyangin throat disease belong to chest heat syndrome, in Taeumin throat disease belong to dry heat syndrome, in Taeyangin throat disease belong to Yul gyuk syndrome 3) In sasang constitutional medicine, medical treatment of throat disease focus on not throat disease but human being and medical treatment of throat disease are almost internal treatment but in Soyangin and Taeumin, medical treatment of throat disease are external treatment.

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A basic study on the diagnostic values of facial color and shape (얼굴의 진단적인 가치에 대한 기초적 연구)

  • Kim, Gyeong Cheol;Lee, Jeong-Won
    • The Journal of the Society of Korean Medicine Diagnostics
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    • v.22 no.1
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    • pp.19-31
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    • 2018
  • For the purpose of the basic educated-establishment on the diagnostic methods of "facial color and shape which reflect human's spiritual essence and personality", we study on the diagnostic value and application of the human face. The study's domain is divided the form and color of human face. And the form and color of human face is respectively observed the diagnostic value and contents. The form of human face reflect plenty the information of the mankind, and the observation of the face is applied to the "Physiognomie" refering to the external features of humans. Therefore the diagnosis on the form of human face is the primary factor in the grouping of five-element human, the discrimination of the Sasang constitution, and the classification of Hyunsang type. The color of human face reflect the physical information of internal organs and the pathological change of disease, therefore we examine the region, character and grade of disease by the inspection of complexion including the changes of color and luster of the facial skin. The inspection on the color is also the primary factor in the grouping of five-element human, the classification of Hyunsang and the differentiation of syndromes. The value of the inspection of complexion including the changes of color and form of the face is widely known. In the future, we think, we need to study more about the theory of the diagnostic value and application of the human face.

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Human Body Mechanics of Pushing and Pulling: Analyzing the Factors of Task-related Strain on the Musculoskeletal System

  • Argubi-Wollesen, Andreas;Wollesen, Bettina;Leitner, Martin;Mattes, Klaus
    • Safety and Health at Work
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    • v.8 no.1
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    • pp.11-18
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    • 2017
  • The purpose of this review is to name and describe the important factors of musculoskeletal strain originating from pushing and pulling tasks such as cart handling that are commonly found in industrial contexts. A literature database search was performed using the research platform Web of Science. For a study to be included in this review differences in measured or calculated strain had to be investigated with regard to: (1) cart weight/ load; (2) handle position and design; (3) exerted forces; (4) handling task (push and pull); or (5) task experience. Thirteen studies met the inclusion criteria and proved to be of adequate methodological quality by the standards of the Alberta Heritage Foundation for Medical Research. External load or cart weight proved to be the most influential factor of strain. The ideal handle positions ranged from hip to shoulder height and were dependent on the strain factor that was focused on as well as the handling task. Furthermore, task experience and subsequently handling technique were also key to reducing strain. Workplace settings that regularly involve pushing and pulling should be checked for potential improvements with regards to lower weight of the loaded handling device, handle design, and good practice guidelines to further reduce musculoskeletal disease prevalence.

Genetically Modified Human Embryonic Stem Cells Relieve Symptomatic Motor Behavior in a Rat Model of Parkinson′s Disease

  • 길광수;이영재;김은영;이창현;이훈택;정길생;박세필;임진호
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.74-74
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    • 2003
  • Embryonic stem cells have several characteristics suitable for cell replacement therapy. To investigate a possibility of using human embryonic stem cell (hESC) as a carrier of therapeutic gene(s), hESC (MB03) was co-transfected with cDNAS coding for tyrosine hydroxylase (TH) and GTP cyclohydrolase Ⅰ (GTPCH Ⅰ) and bulk-selected using neomycin and hygromycin-B. Successful transfection was confirmed by western immunoblotting and RT-PCR. The genetically modified hESC (bk-THGC) relieved apomorphine-induced asymmetric motor behavior by approximately 54% when grafted into striatum of 6-OHDA-denervated rat brain. The number of rotation, however, increased up to 176+18% in 6 weeks when sham-grafted compared with number of rotation before graft. Immunohistochemical staining revealed that the grafted hESC survived and expressed TH for at least 6 weeks while the experiment was continued.

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Stem Cells in Drug Screening for Neurodegenerative Disease

  • Kim, Hyun-Jung;Jin, Chang-Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.1-9
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    • 2012
  • Because the average human life span has recently increased, the number of patients who are diagnosed with neurodegenerative diseases has escalated. Recent advances in stem cell research have given us access to unlimited numbers of multi-potent or pluripotent cells for screening for new drugs for neurodegenerative diseases. Neural stem cells (NSCs) are a good model with which to screen effective drugs that increase neurogenesis. Recent technologies for human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) can provide human cells that harbour specific neurodegenerative disease. This article discusses the use of NSCs, ESCs and iPSCs for neurodegenerative drug screening and toxicity evaluation. In addition, we introduce drugs or natural products that are recently identified to affect the stem cell fate to generate neurons or glia.

Electrophysiological Functions of Intracellular Amyloid β in Specific for Cultured Human Neurones and its Impairment Properties

  • Merlin, Jayalal L.P.
    • Journal of Integrative Natural Science
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    • v.6 no.3
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    • pp.143-150
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    • 2013
  • Prevailing role of intracellular amyloid ${\beta}$ ($iA{\beta}$) in Alzheimer's disease (AD) initiation and progression attracts more and more attention in recent years. To address whether $iA{\beta}$ induces early alterations of electrophysiological properties in cultured human primary neurons, we delivered $iA{\beta}$ with adenovirus and measured the electrophysiological properties of infected neurons with whole-cell recordings. Our results show that $iA{\beta}$ induces an increase in neuronal resting membrane potentials, a decrease in $K^+$ currents and a hyperpolarizing shift in voltage-dependent activation of $K^+$ currents. These results suggest the electrophysiological impairments induced by $iA{\beta}$ may be responsible for its neuronal toxicity.

Copy Number Variations in the Human Genome: Potential Source for Individual Diversity and Disease Association Studies

  • Kim, Tae-Min;Yim, Seon-Hee;Chung, Yeun-Jun
    • Genomics & Informatics
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    • v.6 no.1
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    • pp.1-7
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    • 2008
  • The widespread presence of large-scale genomic variations, termed copy number variation (CNVs), has been recently recognized in phenotypically normal individuals. Judging by the growing number of reports on CNVs, it is now evident that these variants contribute significantly to genetic diversity in the human genome. Like single nucleotide polymorphisms (SNPs), CNVs are expected to serve as potential biomarkers for disease susceptibility or drug responses. However, the technical and practical concerns still remain to be tackled. In this review, we examine the current status of CNV DBs and research, including the ongoing efforts of CNV screening in the human genome. We also discuss the characteristics of platforms that are available at the moment and suggest the potential of CNVs in clinical research and application.

Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example

  • Toner, Cheryl D.
    • Nutrition Research and Practice
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    • v.8 no.4
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    • pp.347-351
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    • 2014
  • Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.