• Journal of Veterinary Science
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• v.22 no.3
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• pp.39.18-39.18
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• 2021

Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.263-275
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• 2022

There is a paucity of detailed data related to the effect of senescence on the mitochondrial antioxidant capacity and redox state of senescent human cells. Activities of TCA cycle enzymes, respiratory chain complexes, hydrogen peroxide (H₂O₂), superoxide anions (SA), lipid peroxides (LPO), protein carbonyl content (PCC), thioredoxin reductase 2 (TrxR2), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPx1), glutathione reductase (GR), reduced glutathione (GSH), and oxidized glutathione (GSSG), along with levels of nicotinamide cofactors and ATP content were measured in young and senescent human foreskin fibroblasts. Primary and senescent cultures were biochemically identified by monitoring the augmented cellular activities of key glycolytic enzymes including phosphofructokinase, lactate dehydrogenase, and glycogen phosphorylase, and accumulation of H₂O₂, SA, LPO, PCC, and GSSG. Citrate synthase, aconitase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, and complex I-III, II-III, and IV activities were significantly diminished in P25 and P35 cells compared to P5 cells. This was accompanied by significant accumulation of mitochondrial H₂O₂, SA, LPO, and PCC, along with increased transcriptional and enzymatic activities of TrxR2, SOD2, GPx1, and GR. Notably, the GSH/GSSG ratio was significantly reduced whereas NAD⁺/NADH and NADP⁺/NADPH ratios were significantly elevated. Metabolic exhaustion was also evident in senescent cells underscored by the severely diminished ATP/ADP ratio. Profound oxidative stress may contribute, at least in part, to senescence pointing at a potential protective role of antioxidants in aging-associated disease.

• Korean Journal of Poultry Science
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• v.50 no.4
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• pp.193-202
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• 2023

Influenza IAVs are encapsulated negative-strand RNA viruses that infect many bird species' respiratory systems and can spread to other animals, including humans. This work reanalyzed previous microarray datasets to identify common and specific differentially expressed genes (DEGs) in chickens, as well as their biological activities. There were 760 and 405 DEGs detected in HPAIV and LPAIV-infected chicken cells, respectively. HPAIV and LPAIV have 670 and 315 DEGs, respectively, with both viruses sharing 90 DEGs. Because of HPAIV infection, numerous genes were implicated in a fundamental biological function of the cell cycle, according to the functional annotation of DEGs. Of the targeted genes, expressions of CDC Like Kinase 3 (CLK3), Nucleic Acid Binding Protein 1 (NABP1), Interferon-Inducible Protein 6 (IFI6), PIN2 (TERF1) Interacting Telomerase Inhibitor 1 (PINX1), and Cellular Communication Network Factor 4 (WISP1) were altered in DF-1 cells treated with polyinosinic:polycytidylic acid (PIC), a toll-like receptor 3 (TLR3) ligand, suggesting that transcription of these genes be controlled by TLR3 signaling. To gain a better understanding of the pathophysiology of AIVs in chickens, it is crucial to focus more research on unraveling the mechanisms through which AIV infections may manipulate host responses during the infection process. Insights into these mechanisms could facilitate the development of novel therapeutic strategies.

• Korean Journal of Environmental Biology
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• v.27 no.3
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• pp.285-291
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• 2009

The effects of water temperature on oxygen consumption (OC) of starry flounder Platichthys stellatus reared in seawater (SW) and freshwater (FW) was performed in closed water-recirculating system containing respiratory chamber. Fish acclimated in separate indoor tanks with SW (nine of fish used, $263.0{\pm}40.4$ g) or FW (nine of fish used, $265.8{\pm}34.8$ g) were sampled. The OC of starry flounder at $15^{\circ}C,\;20^{\circ}C$ and $25^{\circ}C$ were $74.4{\pm}17.0,\;85.9{\pm}15.8,\;98.3{\pm}11.4\;mg\;O_2\;kg^{-1}hr^{-1}$ in SW and $46.7{\pm}12.0,\;63.3{\pm}7.5,\;82.6{\pm}5.3\;mg\;O_2\;kg^{-1}hr^{-1}$ in FW, respectively, showing a linear increase in OC with water temperature. The OC of fish reared in both SW and FW clear diel rhythm, with lower values at daytime and higher values in the night, in accordance with light (09:00~21:00 hr) and dark (21:00~09:00 hr) phases of the diel cycle (12L : 12D) in water temperature at $15^{\circ}C$ and $20^{\circ}C$. However OC of fish reared in both SW and FW showed unclear diel rhythm with light and dark phases of the diel cycle in water temperature at $25^{\circ}C$. Starry flounder reared in FW had higher ventilation rates than those in SW, but SW had higher OC per breath than those in FW.

• Journal of Life Science
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• v.20 no.3
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• pp.437-443
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• 2010

This study was designed to examine the aerobic capacity and ventilatory response during an incremental exercise in elite high school cyclists. Twelve boys ($17{\pm}1\;yr$, $175{\pm}5\;cm$, $70{\pm}9\;kg$) participated in anthropometric measurements, incremental exercise testing, and pulmonary function tests. During incremental exercise testing using a cycle ergometer, their maximal oxygen uptake ($VO_2max$), maximal power output, ventilation, ventilatory equivalents for oxygen ($V_E/VO_2$) and carbon dioxide ($V_E/VCO_2$), respiratory rate, and tidal volume were measured. Time variables such as inspiratory time (Ti), expiratory time (Te), breathing time (Tb), and inspiratory duty cycle (Ti/Tb), as well as inspiratory flow rate ($V_T$/Ti) were assessed. Pulmonary function of vital capacity (FVC), forced expiratory volume in one second ($FEV_1$), $FEV_1$/FVC, and peak expiratory flow were evaluated. Their $VO_2max$, maximal heart rate, and Wmax were $57.5{\pm}3.9\;ml{\cdot}kg^{-1}{\cdot}min^{-1}$, $194.1{\pm}8.6\;beat{\cdot}min^{-1}$, and 452 W, respectively. $VO_2max$ was not related to any anthropometric parameters. Most ventilatory variables progressively increased with exercise intensity. As intensity increased, Ti, Tb, Tb decreased while Ti/Tb was maintained. Below an intensity of 250 W, height, weight, body mass index, and body surface were highly correlated with $V_T$/Ti and Ti/Tb (p<0.05). Collectively, $VO_2max$ appeared to be lower than adult cyclists, suggesting a different pattern of ventilatory control as age advances. Morphological characteristics were not related to $VO_2max$ in the population. Time variables of ventilatory response seemed to be related only at an exercise intensity level of less than 250 W. $V_T$/Ti may be related to exercise endurance capacity, but Ti/Tb was similar to adult cyclists.

• Laboratory Medicine Online
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• v.1 no.1
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• pp.26-34
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• 2011

Background: Laboratory diagnosis of new influenza A (H1N1) is crucial for managing patients and establishing control and prevention measures. We compared the diagnostic accuracies of the real time RT-PCR (rRT-PCR) test recommended for the confirmation of the new flu and the viral culture method used conventionally for viral disease with that of the rapid antigen test (RAT). Methods: We performed RAT, R-mix culture, and real-time PCR by using 861 respiratory samples collected from December 2009 to January 2010 and evaluated the abilities of these methods to detect new influenza A. The relationship among the positive rates of RAT, grades of culture, and the cycle threshold (Ct) values of rRT-PCR was also evaluated. Results: Of the 861 patients, 308 (35.8%) were diagnosed with new influenza A. The sensitivities, specificities, positive predictive values, and negative predictive values of the tests were respectively as follows: 59.7%, 99.5%, 98.4%, and 81.6% for RAT; 93.2%, 100%, 100%, and 96.3% for R-mix culture; and 95.8%, 100%, 100%, and 97.7% for rRT-PCR. Samples with weak positive grade in culture and those with Ct values of 30-37 in rRT-PCR showed positivities as low as 25.3% and 2.3% in RAT, respectively. The hospitalization rate and death rate of the confirmed patients were 3.2% and 0.3%, respectively, and gastrointestinal symptoms were observed in 7.2% of the patients. Conclusions: R-mix culture and rRT-PCR tests showed excellent reliability in the diagnosis of new influenza A and could be very useful, especially for samples with low viral load.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.557-566
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• 2004

Background : To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC Methods : From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results : Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41%. In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion : Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.824-835
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• 1999

Background: Sleep-related breathing disorders are commonly found in patients with chronic renal failure and particularly, sleep apnea may have an influence on the long-term mortality rates in these patients. Maintenance hemodialysis is the mainstay of medical measures for correcting the metabolic derangements of chronic renal failure but it is uncertain whether it may alleviate sleep disorders including sleep apnea. Methods: Forty seven patients on maintenance hemodialysis were surveyed with the sleep questionnaire about their clinical symptoms related to sleep disorders. Among them, 15 patients underwent the polysomnography and their blood levels of urea nitrogen, creatinine, electrolytes and the arterial blood gases in the nights before and following hemodialysis were measured. Results: Forty(85.1%) of the 47 patients complained of the symptoms associated with sleep-wake cycle disturbances, 55.3% experienced snoring and 27.7% reported witnessed apneas. The duration of REM sleep increased significantly in the nights after hemodialysis compared to the nights without hemodialysis(p<0.05) and the percentage of total sleep time comprising NREM sleep decreased significantly in the nights following hemodialysis compared to the nights before hemodialysis(p<0.05). The percentage of total sleep time consisting of the stage 1 and 2 NREM sleep showed the trend for a decrease in the nights after hemodialysis(p=0.051), while the percentage of total sleep time comprising the stage 3 and 4 NREM sleep did not change between nights. The obstructive sleep apnea was more predominant type than the central one in both nights and there were no differences in the apnea index and the apnea-hypopnea index between the nights. The decrease in the blood level of urea nitrogen, creatinine, potassium and phosphorus was observed after hemodialysis(p<0.05), but the differences of parameters measured during polysomnography between the nights did not correlate with the changes of biochemical factors obtained on the two nights. Arterial blood gas analysis showed that pH was significantly greater in the nights after hemodialysis than in the nights before hemodialysis(p<0.05), but there were no correlations between the parameters examined during polysomnography and the parameters of arterial blood gas analysis(p<0.05). Conclusion: These results suggest that chronic renal failure is an important systemic disorder which is strongly associated with sleep disorders. Maintenance hemodialysis, although it is a widely accepted measure to treat chronic renal failure, did not significantly modulate the sleep architecture and the severity of sleep apnea. Thus, taking the patients with chronic renal failure into account, it is advisable to try not only to find a substantial way for correcting metabolic derangements but also to consider the institution of more effective treatments for sleep disorders.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.