• The Korean Journal of Pain
• /
• v.34 no.1
• /
• pp.19-26
• /
• 2021

Background: Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. Methods: Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. Results: The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. Conclusions: D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.7
• /
• pp.835-843
• /
• 2022

Deinococcus radiodurans is an extremophilic bacterium that can thrive in harsh environments. This property can be attributed to its unique metabolites that possess strong antioxidants and other pharmacological properties. To determine the potential of D. radiodurans R1 lysate (DeinoLys) as a pharmacological candidate for inflammatory bowel disease (IBD), we investigated the antiinflammatory activity of DeinoLys in bone marrow-derived dendritic cells (BMDCs) and a colitis mice model. Lipopolysaccharide (LPS)-stimulated BMDCs treated with DeinoLys exhibited alterations in their phenotypic and functional properties by changing into tolerogenic DCs, including strongly inhibited proinflammatory cytokines (TNF-α and IL-12p70) and surface molecule expression and activated DC-induced T cell proliferation/activation with high IL-10 production. These phenotypic and functional changes in BMDCs induced by DeinoLys in the presence of LPS were abrogated by IL-10 neutralization. Furthermore, oral administration of DeinoLys significantly reduced clinical symptoms against dextran sulfate sodium-induced colitis, including body weight loss, disease activity index, histological severity in colon tissue, and lower myeloperoxidase level in mice. Our results establish DeinoLys as a potential anti-inflammatory candidate for IBD therapy.

• Molecules and Cells
• /
• v.45 no.8
• /
• pp.537-549
• /
• 2022

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

• Tuberculosis and Respiratory Diseases
• /
• v.86 no.3
• /
• pp.226-233
• /
• 2023

Background: Inactive or old, healed tuberculosis (TB) on chest radiograph (CR) is often found in high TB incidence countries, and to avoid unnecessary evaluation and medication, differentiation from active TB is important. This study develops a deep learning (DL) model to estimate activity in a single chest radiographic analysis. Methods: A total of 3,824 active TB CRs from 511 individuals and 2,277 inactive TB CRs from 558 individuals were retrospectively collected. A pretrained convolutional neural network was fine-tuned to classify active and inactive TB. The model was pretrained with 8,964 pneumonia and 8,525 normal cases from the National Institute of Health (NIH) dataset. During the pretraining phase, the DL model learns the following tasks: pneumonia vs. normal, pneumonia vs. active TB, and active TB vs. normal. The performance of the DL model was validated using three external datasets. Receiver operating characteristic analyses were performed to evaluate the diagnostic performance to determine active TB by DL model and radiologists. Sensitivities and specificities for determining active TB were evaluated for both the DL model and radiologists. Results: The performance of the DL model showed area under the curve (AUC) values of 0.980 in internal validation, and 0.815 and 0.887 in external validation. The AUC values for the DL model, thoracic radiologist, and general radiologist, evaluated using one of the external validation datasets, were 0.815, 0.871, and 0.811, respectively. Conclusion: This DL-based algorithm showed potential as an effective diagnostic tool to identify TB activity, and could be useful for the follow-up of patients with inactive TB in high TB burden countries.

• IMMUNE NETWORK
• /
• v.24 no.1
• /
• pp.9.1-9.21
• /
• 2024

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

• The Korean Journal of Mycology
• /
• v.39 no.1
• /
• pp.68-77
• /
• 2011

80% methanol and 0.9% neutral saline soluble and hot water substances (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting bodies of Grifola frondosa. In vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cancer cell lines such as Sarcoma 180 and RAW 264.7 at the concentration of 10~2000 ${\mu}g/ml$, but crude polysaccharides from Fr. NaCl was slightly toxic to HT-29 and NIH3T3 at the concentration of 2000 ${\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of 25.0~52.9% in mice previously inoculated with Sarcoma 180. Fr. HW increased the numbers of spleen cells by 1.3 fold at the concentration of 200 ${\mu}g/ml$ compared with control. Fr. NaCl improved the immuno-stimulating activity of B lymphocyte by increasing the alkaline phosphatase activity by 1.5 fold compared with control at the concentration of 200 ${\mu}g/ml$. 10~14 ${\mu}M$ of nitric acid were generated when Fr. NaCl was added to RAW 264.7 at the concentration of 50~500 ${\mu}g/ml$, while the control group produced 4.3 ${\mu}M$ of nitric oxide. The Fr. NaCl, Fr. HW and Fr. MeOH increased the production of TNF-${\alpha}$, IL-$1{\beta}$, Il-2 and IL-6 by more than 1.4 times compared with the control group. The Fr. of MeOH increased the numbers of peritoneal exudate cells and circulating leukocytes by 3.0 and 2.0 folds compared with the control at the concentration of 50 ${\mu}g/ml$, respectively. Therefore, the crude polysaccharides extracted from fruiting bodies of Grifola frondosa could improve antitumor activity of mice.

• The Korean Journal of Mycology
• /
• v.39 no.1
• /
• pp.57-67
• /
• 2011

Agaricus brasiliensis, one of edible mushroom belonging to Basidiomycota, has been used for curing gastric ulcer and stomach cancer of human beings and also known to have good inhibitory effects on sarcoma 180 and Ehrlich carcinoma of mice. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were prepared from fruiting body of the mushroom. ${\beta}$-glucan and total protein contents were identify from fractions of edible mushrooms extract. The ${\beta}$-glucan and protein contents of all fractions of the mushrooms ranged from 21.54~32.31% and 0.16~9.34%, respectively. In vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, NIH3T3 and RAW 264.7 at the concentration of 10~2000 ${\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of 18.8~50.6% in mice previously inoculated with Sarcoma 180. Fr. HW increased the numbers of spleen cell by 1.2 fold at the concentration of 200 ${\mu}g/ml$ compared with control. Fr. MeOH and Na improved the immuno-potentiating activity of B lymphocyte by increasing the alkaline phosphatase activity by 1.6 fold compared with control at the concentration of 50~500 ${\mu}g/ml$. Fr. Na generated 15.9 ${\mu}M$ of nitric oxide (NO) when cultured with RAW 264.7 at the concentration of 200 ${\mu}g/ml$, while lipopolysaccharide, a positive control, produced 3.7 ${\mu}M$. The Fr. NaCl, Fr. HW and Fr. MeOH increased the secretion of TNF-${\alpha}$, IL-$1{\beta}$, Il-2 and IL-6 by 2.2 times compared with the control group. Fr. Na increased the numbers of peritoneal exudate cells by 4 folds at the concentration of 50mg/kg compared with control. Circulating leukocytes increased by 2.7 folds when Fr. HW from A. brasiliensis was inoculated at the concentration of 50 mg/kg body weight. The hematological and blood chemical analysis of the 3 fractions did not show any difference in blood compositions and enzyme activities compared with the control group (p<0.05). Therefore, the experimental results suggested that crude polysaccharides extracted from A. brasiliensis contain antitumor and immuno-potentiating activities against Sarcoma 180 in ICR mice.

• Journal of Radiation Protection and Research
• /
• v.13 no.1
• /
• pp.31-41
• /
• 1988

In case of the acute intake of radionuclide, an early medical treatment may be necessary, but the little is established the procedures to decontaminate the victims of internal contamination in Korea. The purpose of the present investigation is to study chemical agents to remove radiocobalt from the victims and to provide a more reliable procedure for the treatment. The removals of radiocobalt from the NIH-CGP)mice injected intraperitoneally with $1{\mu}Ci$ of $^{58}Co$ as $CoCl_2$ were investigated with doses of either $CaNa_3$ DTPA 8.4mg/0.2ml saline, $CoNa_3$ DTPA 8.4mg/0.2ml saline, or saline 5ml. The radioactivity was determined by MCA and Ge-detector on 4, 8, 12, 48 hours and 7 days for the whole body, organ distribution and urine excretion. Six mice per each group were sacrificed for the measurement of cobalt retention in the parenchymal tissue. The cobalt trisodium chelate had a pronounced effect on reducing the whole body retention and increasing the excretion rate. Regarding to the systemic protective effects, $CoNa_3$ DTPA, $CaNa_3$ DTPA and saline were effected significantly in order. In conclusion, the extrapolations from these results to human were suggested that the rapid administration of cobalt trisodium chelate and an amount of saline to the contaminated person after internal contamination of radiocobalt were markedly increasing the decontamination effects.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.12 no.2
• /
• pp.256-262
• /
• 2001

Objective：The enlargement of the lateral ventricle is well established finding in adult-onset schizophrenia, but in the patients with early-onset psychotic disorder(EOPD) is still controversal. To identify structural abnormalities of the lateral ventricle in patients with EOPD and difference of the brain developmental course in EOPD group, planimetrical assessment of the lateral ventricle was conducted by means of retrospective quantitative neuroimaging. Methods：The brain MR images of 14 patients with EOPD(mean age $14.0{\pm}2.1$ years) who met the DSM-III-R diagnostic criteria for schizophrenia and bipolar disorder and 24 control subjects with simple headache(mean age $10.0{\pm}2.1$ years) were collected. Single best view for the lateral ventricle, one axial slice was selected for analysis. MR images were redigitalized with flatbed scanner and data were analyzed with NIH IMAGE software. Results：In the patients with EOPD, there were significant correlations between aging and lateral ventricular sizes and between aging and ventricular brain ratio(VBR). The statistical significance of normal asymmetry of the lateral ventricle was not observed for the EOPD group. The EOPD group had larger lateral ventricular sizes and VBR than control group, but these results were not statistically significant. Conclusion：These findings suggest that the brain abnormalities in patients with EOPD progress from the earlier course of the disorders and the course of brain development in EOPD group is different from control group.

• Journal of the Korean Society of Radiology
• /
• v.14 no.5
• /
• pp.603-612
• /
• 2020

This study has a purpose to look into the effect of the relationship between the Tube current (mA) and SOD(Source to Object Distance), which is a parameter of lower limb angiography examination, and the dilution rate of the contrast medium concentration (300, 320, 350) on the image. To that end, using 3 mm vessel model water phantom, a vessel model custom made in the size of peripheral vessel diameter, this study measured relationships between change of parameters, such as tube current (mA), SOD and varying concentrations (300, 320, 350) of contrast medium dilution into SNR and CNR values while analyzing the coefficients of variance(cv<10). The software used to measure SNR and CNR values was Image J 1.50i from NIH (National Institutes of Health, USA). MPV (mean pixel value) and SD (standard deviation) were used after verifying numerically the image signal for region of interest (ROI) and background on phantom from the DICOM (digital imaging and communications in medicine) 3.0 file transmitted to PACS. As to contrast medium dilution by the change of tube current, when 146 mA and 102 mA were compared, For both SNR and CNR, the coefficient of variation value was less than 10 until the section of CM: N/S dilution (100% ~ 30% : 70%) but CM: N/S dilution rate (20%: 80% ~ 10% : 90%) the coefficient of variation was 10 or more. As to contrast medium dilution by concentration for SOD change, when SOD's (32.5 cm and 22.5 cm) were compared,For both SNR and CNR, the coefficient of variation value was less than 10 until the section of CM: N/S dilution (100% ~ 30% : 70%) but CM: N/S dilution rate (20%: 80% ~ 10% : 90%) the coefficient of variation was 10 or more. As to contrast medium dilution by concentration for SOD change, when SOD's (32.5 cm and 12.5 cm) were compared,For both SNR and CNR, the coefficient of variation value was less than 10 until the section of CM: N/S dilution (100% ~ 30% : 70%) but CM: N/S dilution rate (20%: 80% ~ 10% : 90%) the coefficient of variation was 10 or more. As a result, set a low tube current value in other tests or procedures including peripheral angiography of the lower extremities in the intervention, and make the table as close as possible to the image receiver, and adjust the contrast agent concentration (300) to CM: N/S dilution (30%: 70%). ) Is suggested as the most efficient way to obtain images with an appropriate concentration while simultaneously reducing the burden on the kidney and the burden on exposure.