• 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.

• Journal of Korean Society for Atmospheric Environment
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• v.19 no.5
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• pp.551-560
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• 2003

Particle deposition in human lungs was investigated theoretically by using asymmetric five-lobe lung model. The volumes of each of the five lobes were different, thereby forming an asymmetric lung structure. The tidal volume and flow rate of each lobe were scaled according to lobar volume. The total and regional deposition with various breathing patterns were calculated by means of tracking volume segments and accounting for particle loss during inhalation and exhalation. The deposition fractions were obtained for each airway generation and lung lobe, and dominant deposition mechanisms were investigated for different size particles. Results show that the tidal volume and flow rate have a characteristic influence on particle deposition. The total deposition fraction increases with an increase in tidal volume for all particle sizes. However, flow rate has dichotomous effects: a higher flow rate results in a sharp increase in deposition for large size particles, but decreases deposition for small size particles. Deposition distribution within the lung shifts proximally with higher flow rate whereas deposition peak shifts to the deeper lung region with larger tidal volume. Deposition fraction in each lobe was proportional to its volume. Among the three main deposition mechanisms, diffusion was dominant for particles < 0.5 ${\mu}{\textrm}{m}$ whereas sedimentation and impaction were most influential for larger size particles. Impaction was particularly dominant for particles> 8 ${\mu}{\textrm}{m}$. The results may prove to be useful for estimating deposition dose of inhaled pollutant particles at various breathing conditions.

• Korean Journal of Veterinary Research
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• v.19 no.1
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• pp.1-8
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• 1979

Detailed human gross anatomic structures have been characterized. No similar data are available in nonhuman primate species in spite of close phylogenic similarity found between man and nonhuman primates. The ever increasing incidence of lung cancer and air pollution related respiratory ailments found in man emphasizes the need for an ideal animal model for studying pathogenesis of these various human pulmonary diseases. Thus, detailed investigation of pulmonary structures found in various species of nonhuman primates is warranted. For determining primate gross pulmonary anatomic structure, published works concerning the number of tracheal cartilage, angle of tracheal bifurcation, caliber of trachea, lung lobe and bifurcation position of trachea recorded for several species of nonhuman pimates, were reviewed. Limited information is available concerning the number of tracheal cartilage, width of tracheal cartilage, angle of bronchus, caliber of trachea and bronchus, and the bifurcation position of the trachea including the length of bronchus on nonhuman primates. Since scanty data have been gathered with no specific reference to their age, sex and body weight, they have no comparative values.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1120-1128
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• 2005

To investigate the toxic of herbs used in , the author analyzed herbs with toxic recorded in , , after searched toxic herbs literarily. Herbs with toxicity recorded in both and were total 17 species, and recorded in were total 13 species, and recorded in were total 12 species. The major cause that herbs generates a side effect in a human body is implicit use and abuse, inadequate processing the herbs, use of quack medicines of herbs and clinical use which is improper in symptoms and internal use, differences of constitution. The major toxic component in herbs is an alkaloid, essential oil and hydrargyrum (Hg), and the main invasion route of toxic herbs in human body is the liver, kidney, lungs, and gastrointestinal tract.

• Neonatal Medicine
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• v.18 no.2
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• pp.165-176
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• 2011

The pathologic hallmark of new bronchopulmonary dysplasia (BPD) is an arrest in alveolarization and vascular development. Alveoli are the fully mature gas-exchange units and alveolarization denotes the process through which the developing lung attains its fully mature structure. In human, alveolarization is mainly a postnatal event and begins in utero around 35 postmenstrual weeks and continues to 2 postnatal years. Beginning of respiration with very immature lungs as a result of preterm delivery renders the immature lung to be exposed to various injuries such as mechanical stretch, hyperoxia, infection/inflammation and leads to a disruption of normal alveolarization process, which is a main pathologic finding of BPD. Better understanding of the control mechanisms of normal alveolarization process should help us to figure out the pathophysiology of BPD and discover effective preventive or therapeutic measures for BPD. In this review, the pathologic evolution of BPD from 'old' to 'new' BPD, the detailed mechanisms of normal alveolarization, and the factors that disrupt normal alveolarization will be discussed.

• BMB Reports
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• v.36 no.1
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• pp.49-59
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• 2003

Platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. The vital functions of PDGFs for angiogenesis, as well as development of kidney, brain, cardiovascular system and pulmonary alveoli during embryogenesis, have been well demonstrated by gene knock-out approaches. Clinical studies reveal that aberrant expression of PDGF and its receptor is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs, kidneys and joints, and neoplasia. PDGF contributes to cancer development and progression by both autocrine and paracrine signaling mechanisms. In this review article, important features of the PDGF isoforms and their cell surface receptor subunits are discussed, with regards to signal transduction, PDGF-isoform specific cellular response, and involvement in angiogenesis, and tumorstromal interactions.

• Biomedical Science Letters
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• v.24 no.4
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• pp.285-291
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• 2018

Gremlin-1 (GREM1) has been defined as an antagonist of bone morphogenetic proteins (BMPs), particularly during embryonic development and tissue differentiation. However, recent studies have shown that GREM1 has BMPs-dependent or -independent functions in diverse human diseases. GREM1 plays a key role in the process of organ fibrosis, including lungs, kidneys, and so on. The GREM1-induced fibrosis typically promotes the development of other diseases, such as pulmonary hypertension, renal inflammation, and diabetic nephropathy. More recently, considerable evidence has been reported showing that GREM1 is involved in the promotion and/or progression of tumors in vitro and in vivo. It also performs an oncogenic role in the maintenance of cancer stem cells. Although GREM1 is known to function in a variety of diseases, here we focus on the role of GREM1 in cancer, and suggest GREM1 as a potential therapeutic target in certain types of cancer.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.415-424
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• 2023

Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

• Molecules and Cells
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• v.39 no.3
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• pp.242-249
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• 2016

A balance between production and degradation of reactive oxygen species (ROS) is critical for maintaining cellular homeostasis. Increased levels of ROS during oxidative stress are associated with disease conditions. Antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD), in the extracellular matrix (ECM) neutralize the toxicity of superoxide. Recent studies have emphasized the importance of EC-SOD in protecting the brain, lungs, and other tissues from oxidative stress. Therefore, EC-SOD would be an excellent therapeutic drug for treatment of diseases caused by oxidative stress. We cloned both the full length (residues 1-240) and truncated (residues 19-240) forms of human EC-SOD (hEC-SOD) into the donor plasmid pFastBacHTb. After transposition, the bacmid was transfected into the Sf9-baculovirus expression system and the expressed hEC-SOD purified using FLAG-tag. Western blot analysis revealed that hEC-SOD is present both as a monomer (33 kDa) and a dimer (66 kDa), as detected by the FLAG antibody. A water-soluble tetrazolium (WST-1) assay showed that both full length and truncated hEC-SOD proteins were enzymatically active. We showed that a potent superoxide dismutase inhibitor, diethyldithiocarbamate (DDC), inhibits hEC-SOD activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1254-1269
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• 2004

The contents of Fang Sheng Shuai Lun(방성쇠론) is the rise and fall of five viscera(heart, lungs, liver, spleen, kidneys)'s Yin-Yang Energy is related to change of human body's condition and how to diagnose this change. This chapter comment on change of Yin-Yang Energy under seasons and age, change of dream under deficient of five viscera's chi, notice of diagnosis and diagnostic technique on deficient of five viscera's chi.