Hyung-Jun Kim;Sohyun Park;Seonghyeon Jeong;Jihoon Kim;Young-Jae Cho
International Journal of Stem Cells
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v.17
no.1
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pp.30-37
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2024
The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues. Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.
Objectives The object of this study was to observe the effects of Hyeongbangjihwhang-tang (HB; Soyangin prescription) on the 5/6 NTX induced CRF rats. Methods Each of Hyeongbangjihwhang-tang aqueous extracts 200mg/kg were orally administered once a day for 35 days from 4 weeks after 5/6 NTX surgery. Four groups, each of 8 rats per group were used in this study, were sham group, CRF group, ${\alpha}$-Tocoperol group and HB group. Changes on the left remnant kidney weights, serum BUN, creatinine levels, caspase-3, PARP immunoreactivities were observed to nephroprotective effects, and relative immunomodulatory effects were monitored based on the changes of lymphatic organ weights and splenic cytokine contents. In addition, the changes on the kidney MDA, GSH contents and SOD, CAT activities were also calculated for antioxidant effects, and the effects on the CRF related cachexia were demonstrated based on the changes of body and epididymal fat pad weights, serum TG, TC, LDL and HDL levels. Results and Conclusions 1) HB was significantly decreased the left remnant kidney weights, serum BUN, creatinine levels and caspase-3, PARP immunoreactivities. 2) HB was significantly increased lymphatic organ weights and splenic cytokine contents. 3) HB was significantly increased body and epididymal fat pad weights, and was significantly decreased serum TG, TC, LDL and HDL levels. 4) HB was significantly decreased MDA contents, and was significantly increased GSH contents and SOD, CAT activities. The results obtained in this study suggest that HB significantly retarded immunosuppressions and cachexia related to the 5/6 NTX induced CRF through modulations of oxidative defense systems. Especially HB showed the highest favorable effects more than those of ${\alpha}$-tocoperol.
There is much evidence suggesting that compounds present in soybean can prevent cancer in many different organ systems. Especially, soybean is one of the most important source of dietary saponins, which have been considered as possible anticarcinogens to inhibit tumor development and major active components contributing to the cholesterol-towering effect. Also they were reported to inhibit of the infectivity of the AIDS virus (HIV) and the Epstein-Barr virus. The biological activity of saponins depend on their specific chemical structures. Various types of triterpenoid saponins are present in soy-bean seeds. Among them, group B soyasaponis were found as the primary soyasaponins present in soybean, and th e 2, 3-dihydro-2, 5-dihydroxy-6- methyl-4H-pyran-4-one(DDMP)-conjugated soyasaponin $\alpha\textrm{g}$, $\beta\textrm{g}$, and $\beta$ a were the genuine group B saponins, which have health benefits. On the other hand, group A saponins are responsible for the undesirable bitter and astringent taste in soybean. The variation of saponin composition in soybean seeds is explained by different combinations of 9 alleles of 4 gene loci that control the utilization of soyasapogenol glycosides as substrates. The mode of inheritance of saponin types is explained by a combination of co-dominant, dominant and recessive acting genes. The funtion of theses genes is variety-specific and organ specific. Therefore distribution of various saponins types was different according to seed tissues. Soyasaponin $\beta\textrm{g}$ was detected in both parts whereas $\alpha\textrm{g}$ and $\beta$ a was detected only in hypocotyls and cotyledons, respectively. Soyasaponins ${\gamma}$g and $\gamma\textrm{g}$ were minor saponin constituents in soybean. In case group A saponins were mostly detected in hypocotyls. Also, the total soyasaponin contents varied among different soy-bean varieties and concentrations in the cultivated soy-beans were 2-fold lower than in the wild soybeans. But the contents of soyasaponin were not so influenced by environmental effects. The composition and concentration of soyasaponins were different among the soy products (soybean flour, soycurd, tempeh, soymilk, etc.) depending on the processing conditions.
The immune system is partially under the control of the sympathetic and parasymphathetic nervous systems through the regulatory feedback loop. Methamphetamine (MA) is a neurotoxic chemical which affects the neurotransmitter system. The objective of this study was to investigate the immunotoxic effect of MA on the major immune target organ and lymphocyte proliferation to the various mitogens. Female Balb/C mice, 15 to 20 g, were injected subcutaneously with 0, 0.5, or 5 mg MA/kg for 14 consecutive days. In MA treated mice, the body weight gain and relative spleen and thymus weight were decreased in doserelated manner. Histopathologically, there was a paucity of lymphold follicles and germinal centers in the spleen, and thymic cortical atrophy with lymphophagocytosis was prominent. Apoptosis also occurred in germinal centers of spleen and thymic cortex. The threshold and peak of lymphocyte proliferation at various concentration of mitogens showed similar patterns. However, the response to lipopolysaccaride (LPS) and pokeweed mitogen (PWM) in the 5 mg MA/kg treated group showed threshold and peak proliferation at high concentration of mitogens (25${\mu}g$ LPS/ml for MA vs 15${\mu}g$ LPS/ml for control; 60${\mu}g$ PWM/ml for MA vs 45${\mu}g$ PWM/ml for control), which suggest that MA impairs T cell dependent-B cell function. This preliminary study indicated that MA affected the lymphold organs and immune function.
The conventional delivery quality assurance (DQA) process for RapidArc (Varian Medical Systems, Palo Alto, USA), has the limitation that it measures and analyzes the dose in a phantom material and cannot analyze the dosimetric changes under the motional organ condition. In this study, a DQA method was designed to overcome the limitations of the conventional DQA process for internal target volume (ITV) based RapidArc. The dynamic DQA measurement device was designed with a moving phantom that can simulate variable target motions. The dose distribution in the real volume of the target and organ-at-risk (OAR)s were reconstructed using 3DVH with the ArcCHECK (SunNuclear, Melbourne, USA) measurement data under the dynamic condition. A total of 10 ITV-based RapidArc plans for liver-cancer patients were analyzed with the designed dynamic DQA process. The average pass rate of gamma evaluation was $81.55{\pm}9.48%$ when the DQA dose was measured in the respiratory moving condition of the patient. Appropriate method was applied to correct the effect of moving phantom structures in the dose calculation, and DVH data of the real volume of target and OARs were created with the recalculated dose by the 3DVH program. We confirmed the valid dose coverage of a real target volume in the ITV-based RapidArc. The variable difference of the DVH of the OARs showed that dose variation can occur differently according to the location, shape, size and motion range of the target. The DQA process devised in this study can effectively evaluate the DVH of the real volume of the target and OARs in a respiratory moving condition in addition to the simple verification of the accuracy of the treatment machine. This can be helpful to predict the prognosis of treatment by the accurate dose analysis in the real target and OARs.
1. Objectives: This study reviews the general theory on Li-Qi (理-氣) found in Dongmu Lee Jema (東武 李濟馬) and Nosa Gi Jeongjin (蘆沙 奇正鎭)'s works and explores the associations between their philosophical systems. 2. Methods: The main ideas on Predisposition (氣稟論) found in Dongmu's works were explored in connection with the Li-Qi (理-氣) theory and compared with the perspectives suggested by Nosa. 3. Results and Conclusions 1) Nosa criticized the "weakened supervision of Li (理)" and the "separation of Li (理) and Qi (氣)", proposing that this problem can be overcome through "mutual embracement of Li and its manifestations (理分圓融 理分相涵)". 2) When Dongmu's theory on Predisposition (氣稟論) is interpreted in terms of Li-Qi (理-氣), the Seong-Li (laws governing the organ scheme) (性理(臟理)) represents the Li (理) while the formational variations in organ scheme(臟局短長) and and the level of self-cultivation (心地淸濁) represents the Qi (氣). 3) The concept of "Diversification of Li (理之異)", bearing similarities to Nosa's Li-Qi (理-氣) theory, was introduced for the first time in Dongmu's theory on Predisposition (氣稟論), which presumably built the fundamental theories in the Sasang Constitutional Typology. 4) Within Dongmu's theory of Predisposition (氣稟論) can be found a dichotomous division of "similitude between the morally unaccomplished and the morally accomplished" in the ontological plane and "dissimilitude between the morally unaccomplished and the morally accomplished" in the axiological plane; this dichotomy is more extensive and developed compared to Nosa's attempt to find a consistent logic in both the ontological and axiological plane through a Li-Qi (理-氣) structure with Li-predominance.
BACKGROUND/OBJECTIVES: Vitamin D is a pleiotropic hormone that affects various body organ systems. We evaluated the prevalence of a vitamin D deficiency (VDD) and its potential role in the clinical condition of critically ill Korean children. SUBJECTS/METHODS: Patients under 18 years old with a 25(OH) vitamin D measurement on the first day of PICU admission were included from among the children admitted to the pediatric intensive care unit (PICU) of our tertiary children's hospital between October 2017 and January 2019. RESULTS: A total of 172 pediatric patients were enrolled. The mean 25(OH) vitamin D level was 17.5 ± 12.8 ng/mL. There was a 65.1% prevalence of VDD (25(OH) vitamin D level < 20 ng/mL). VDD was associated with age at PICU admission, gastrointestinal/hepatobiliary disorders, International Society of Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH DIC) score, pediatric multiple organ dysfunction syndrome (pMODS) score and with several laboratory test findings including hemoglobin, platelet, C-reactive protein, serum albumin, total bilirubin, prothrombin time, and anti-thrombin III levels. Most of these parameters also showed significant linear correlations with the 25(OH) vitamin D level (P < 0.05). However, no statistically meaningful association was found between VDD and other clinical conditions such as the need for a mechanical ventilator, requirement for vasoactive drugs, duration of the PICU and hospital stays, or PICU mortality. CONCLUSION: There is a high prevalence of VDD in critically ill Korean children. There were significant associations between the 25(OH) vitamin D level and gastrointestinal/hepatobiliary disorders, the pMODS score and with coagulation related factors. Further large-scale studies with more specific subgroup analyses are required to more precisely assess the clinical implications of VDD in critically ill pediatric patients.
Extra-corporeal membrane oxygenation (ECMO) has the potential to rescue patients in cardiac arrest or respiratory failure. ECMO has two systems such as veno-arterial and veno-venous circulation. In cardiac arrest resulting from acute myocardial infarction, veno-arterial ECMO is mandatory for systemic circulation and oxygenation. A 75-year old female patient underwent primary coronary intervention for acute myocardial infarction. Despite successful revascularization, recurrent ventricular tachycardia and heart failure were progressing. We performed a veno-arterial ECMO through the femoral artery and vein, then the patient seemed to be stable clinically. However, laboratory studies, echocardiography, and vital signs indicated multi-organ failure and decreasing cardiac function. We found out an error that we performed veno-venous ECMO instead of veno-arterial ECMO. We added a femoral artery cannula and exchange the circuit system to veno-arterial ECMO. While the systemic circulation seemed to be recovered, the left ventricular function was decreased persistently. A hypovolemia resulting from pulmonary hemorrhage was occurred, which lead to ECMO failure. The patient died of cardiac arrest and multi-organ failure 23 hours after ECMO. Because the color of arterial and venous circuits represent the position and efficacy of ECMO, if unexpected or abnormal circuit colors are detected, prompt and aggressive evaluation for ECMO function is mandatory.
Fabry disease (FD), a rare X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A gene gene encoding α-galactosidase A (α-Gal A). The functional deficiency of α-Gal A results in progressive accumulation of neutral glycosphingolipids, causing multi-organ damages including cardiac, renal, cerebrovascular systems. The current treatment is comprised of enzyme replacement therapy (ERT), oral pharmacological chaperone therapy and adjunctive supportive therapy. ERT has been introduced 20 years ago, changing the outcome of FD patients with proven effectiveness. However, FD patients have many unmet needs. ERT needs a life-long intravenous therapy, inefficient bio-distribution, and generation of anti-drug antibodies. Migalastat, a pharmacological chaperone, augmenting α-Gal A enzyme activity only in patients with mutations amenable to the therapy, is now available for clinical practice. Furthermore, these therapies should be initiated before the organ damage becomes irreversible. Development of novel drugs aim at improving the clinical effectiveness and convenience of therapy. Clinical trial of next generation ERT is underway. Polyethylene glycolylated enzyme has a longer half-life and potentially reduced antigenicity, compared with standard preparations with longer dosing interval. Moss-derived enzyme has a higher affinity for mannose receptors, and seems to have more efficient access to podocytes of kidney which is relatively resistant to reach by conventional ERT. Substrate reduction therapy is currently under clinical trial. Gene therapy has now been started in several clinical trials using in vivo and ex vivo technologies. Early results are emerging. Other strategic approaches at preclinical research level are stem cell-based therapy with genome editing and systemic mRNA therapy.
Kim, Kyung Ah;Na, Kyung Soo;Seo, Seok Jin;Lee, Je Hee
The Journal of Korean Society for Radiation Therapy
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v.29
no.1
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pp.57-68
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2017
Purpose: The purpose of this study was to compare volumetric modulated arc therapy(VMAT) with fixed-field intensity modulated radiation therapy(IMRT) using non-coplanar beam when the shape of target is irregular and the location is adjacent to organ at risk(OAR). Materials and Methods: The subjects of this study were a total of 6 patients who had radiation therapy for whole scalp(2 patients), partial scalp(2 patients), and whole ventricle(2 patients) by True Beam STX(Varian Medical Systems, USA). VMAT plans consisted of coplanar or non-coplanar arcs which can minimize the volume of OAR included in beamlets. All fixed-field IMRT plans consisted of non-coplanar beams using more than 2 angles of Couch. Results: The VMAT and IMRT plans were compared with regard to the maximum dose of both lens, both optic nerves, optic chiasm, and brain stem and the mean dose of both eyeballs and hippocampus. VMAT plans showed higher dose than ncIMRT plans at more than 6 of all OARs in every patient, and the ratio was from 1.1 times to 8.2 times. In case of total scalp and partial scalp, the volume of brain which received more than 20 Gy in the VMAT plans was 2 times larger than the volume in the ncIMRT plans. In case of whole ventricle, there was no significant difference. Target coverage was satisfied in both plans($PTV_{100%}=95%$). The maximum dose in target volume and required monitor unit(MU) of ncIMRT were higher than them of VMAT plans. Conclusion: Even though ncIMRT is less efficient than VMAT with regard to required MU and treatment time, the dose to OARs is much lower than VMAT and PTV Coverage is similar with VMAT. If the shape of target is irregular and location is adjacent to OAR, comparison VMAT plan with ncIMRT plan deserves to be considered.
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