• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.1
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• pp.28-34
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• 2022

Echinacea purpurea (Asteraceae family) is widely used in the European countries and the United States due to its proven immune enhancement and anti-inflammatory effects. Echinacea purpurea has been reported prevent and treat upper respiratory tract infections and common cold, but the underlying molecular mechanisms are not well understood. In the present study, we examined the anti-inflammatory effects and molecular mechanisms of Echinacea purpurea (EP) extract using lipopolysaccharide (LPS)-stimulated signal pathways in RAW264.7 cells. Our results suggest that EP extract exerts anti-inflammatory effects by down-regulating the expression of LPS-induced toll-like receptor 4 (TLR4), subsequently inhibiting the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways and suppression of the release of pro-inflammatory cytokines. These results suggest that EP extract is a potential therapeutic agent for inflammatory diseases.

• Journal of the korean academy of Pediatric Dentistry
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• v.45 no.4
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• pp.508-513
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• 2018

Tidal volume by sevoflurane in small amounts is stable due to the increase in the breathing rate. But alveolus ventilation decreases due to sevoflurane as the degree of sedation increases; this ultimately causes $PaCO_2$ to rise. The occurrence of suppression of breath increases the risk of severe hypoxia and hypercapnia in deeply sedated patients with disabilities. Sevoflurane inhalation anesthesia has a number of risks and may have unexpected problems with hemodynamic changes depending on the underlying state of the body. This study was conducted to examine the stability of internal acid-base system caused by respiratory depression occurring when patients with disabilities are induced by sevoflurane. Anesthetic induction was carried out by placing a mask on top of the patient's face and through voluntary breathing with 4 vol% of sevoflurane, 4 L/min of nitrous oxide, and 4 L/min of oxygen. After the patient's loss of consciousness and muscle relaxation, IV line was inserted by an expert and intravenous blood gas was analyzed by extracting blood from vein. In a deeply sedated state, the average amount of pH of the entire patients was measured as $7.36{\pm}0.06$. The average amount of $PvCO_2$ of the entire patients was measured as $48.8{\pm}8.50mmHg$. The average amount of $HCO_3{^-}$ of the entire patients was measured as $27.2{\pm}3.0mmol/L$. In conclusion, in dental treatment of patients with disabilities, the internal acid base response to inhalation sedation using sevoflurane is relatively stable.

• Tuberculosis and Respiratory Diseases
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• v.70 no.2
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• pp.132-138
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• 2011

Background: Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily. A few studies have examined the role of maspin in tumor suppression of non-small cell lung cancer (NSCLC); however, its role in the development and progression of NSCLC still remains controversial. We evaluated the immunohistochemical expression of maspin in order to elucidate its clinical significance in NSCLC. Methods: We analyzed 145 patients with pathologically confirmed NSCLC, including 66 cases of squamous cell carcinomas (SCCs) and 79 cases of adenocarcinomas (ADCs). We performed a immuno-histochemical stain with maspin and PCNA (proliferating cell nuclear antigen) using tissue microarray blocks. Results: There were 108 men and 37 women in the study population. The mean age of patients in the study was 63.7 years (range, 40.0~82.0; median, 65.0). The proportion of maspin expression was significantly higher in SCCs (52/66, 78.8%; p<0.01) than in ADCs (17/79, 21.5%; p<0.01). Maspin expression was not associated with PCNA (p=0.828), lymph node involvement (p=0.483), or tumor stage (p=0.216), but showed correlation with well-to-moderate tumor differentiation (p=0.012). There was no observed correlation between maspin expression and survival with NSCLC (p=0.218). Conclusion: The present study suggests that maspin expression was significantly higher in SCCs than in ADCs and was associated with low histological grade. However, maspin expression was not an independent factor to predict a prognosis in NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.75 no.2
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• pp.59-66
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• 2013

Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.618-623
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• 1995

Cryptococcosis is a systemic mycosis that most often involves the lungs and central nervous system and, less frequently, the skin, skeletal system, and prostate gland. Cryptococcus neoformans, the causative organism, is a yeastlike round or oval fungus, 4 to $6{\mu}m$ in diameter, which is surrounded by a polysaccharide capsule and reproduces by budding and found in soil and other environmental areas, especially those contaminated by pigeon droppings. Humans and animals acquire infection after inhalation of aerosolized spores. Condition or factors that predispose to cryptococcosis include corticosteroid therapy, lymphoreticular malignancies, HIV infection, and sarcoidosis etc. We discribed a case of cryptococcosis involving lung and CNS coincidently without specific underlying disease and the literature on subject were reviewed. A fifty-six year-old previously healthy female presented with headache of 3 months of duration. She had no history suggesting immunologic suppression and we could not find any abnormal laboratory findings including blood sugar, serum immunoglobulin and complement level, HIV antibody, and T cell subsets. Chest roentgenogram and CT scan showed a solitary soft tissue mass in LUL with distal pneumonitis. Brain MRI showed granulomatous lesion in cerebellum and parasagittal cortex of right frontal lobe. The diagnosis was made by bronchoscopic brushing cytology, transthoracic fine needle aspiration, and sputum KOH mount and culture. She was treated 6 weeks course of Amphotericin B and switched to oral fluconazole therapy for 3 months. Her symptoms and X-ray findings were improved gradually and she is now under regular clinical follow up.

• Journal of Veterinary Clinics
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• v.36 no.6
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• pp.306-313
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• 2019

It is important to identify the most suitable anesthetic agent that has minimal side effects to be able to control and perform surgeries on bears. In this study, we examined and compared the induction and recovery times as well as the physiological changes occurring during anesthesia induced by medetomidine-zolazepam/tiletamine (MZT) and xylazine-zolazepam/tiletamine (XZT) at general anesthesia for laparoscopic salpingectomy in 326 female Asiatic black bears. The body temperature, heart rate, respiratory rate, and levels of PaO₂ and EtCO₂ were the physiological changes measured during surgical procedures in female bears after anesthesia. In addition, the levels of pO₂, pCO₂, and sO₂ were measured using a portable blood gas analyzer. To induce recovery from anesthesia, bears anesthetized with MZT were intravenously administered atipamezole and bears anesthetized with XZT were intravenously administered yohimbine. The combination MZT, at dosages of 0.019 ± 0.001 mg/kg for medetomidine and 1.4 ± 0.1 mg/kg for ZT, or the combination XZT, at dosages of 2.0 ± 0.1 mg/kg for xylazine and 3.0 ± 0.1 mg/kg for ZT, proved to be reliable and effective in anesthetizing Asiatic black bears for a 40-min handling period for routine clinical procedures. The average anesthesia induction times were 16.5 ± 0.95 min for the bears in the MZT group and 12.0 ± 0.44 min for those in the XZT group. A significant difference was noted between the two drugs (P < 0.001) in terms of the average anesthesia induction time. The anesthesia induction time was shorter for bears with lower body weights than those with higher body weights (P < 0.05). The recovery time of MZT was significantly faster than that of XZT (11.3 ± 0.45 min vs. 18.5 ± 0.83 min) (P < .001). The bears anesthetized with MZT exhibited lower cardiopulmonary suppression than those anesthetized with XZT (P < 0.05). The body temperatures and EtCO₂ of bears in the M ZT group were significantly lower than those in the XZT group as time progressed after anesthesia (P < 0.05). The average pO₂ before the bears were supplied with oxygen was 64.8 ± 3.7 mmHg, but it increased to 211.5 ± 42.5 mmHg afterwards (P < 0.001). In conclusion, our results indicate that bears anesthetized with MZT have longer anesthesia induction time, shorter recovery time, slower heart and respiratory rates, and lower body temperatures and EtCO₂ than those anesthetized with XZT. These findings suggest that XZT is preferable to MZT, warranting further research on its uses and clinical responses in bears.

• International Journal of Stem Cells
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• v.15 no.2
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• pp.203-216
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• 2022

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods and Results: Non-apoptotic concentrations of DEP (10 ㎍/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 ㎍/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions: Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3253-3258
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• 2012

Objective: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT) plus chemotherapy versus WBRT alone for treating brain metastases (BM) from lung cancer by performing a meta-analysis based on randomized controlled trials (RCTs). Methods: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM, CNKI, and VIP databases were searched for relevant RCTs performed between January 2000 and March 2012. After quality assessment and data extraction, the meta-analysis was performed using the RevMan 5.1 software, with funnel plot evaluation of publication bias. Results: 19 RCTs involving 1,343 patients were included. The meta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy was more effective with regard to the objective response rate (OR = 2.30, 95% CI = 1.79 - 2.98; P < 0.001); however, the incidences of gastrointestinal reactions (RR = 3.82, 95% CI = 2.33 - 6.28, P <0.001), bone marrow suppression (RR = 5.49, 95% CI = 3.65 - 8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39 - 86.59; P = 0.20), leukopenia (RR = 3.13, 95% CI = 1.77 - 5.51; P < 0.001), and neutropenia (RR = 2.75, 95% CI = 1.61 - 4.68; P < 0.001) in patients treated with WBRT plus chemotherapy were higher than with WBRT alone. There was no obvious publication bias detected. Conclusion: WBRT plus chemotherapy can obviously improve total efficacy rate, butalso increases the incidence of adverse reactions compared to WBRT alone. From the limitations of this study, more large-scale, high-quality RCTs are suggested for further verification.

• Toxicological Research
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• v.27 no.2
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• pp.95-102
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• 2011

The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for various respiratory disorders were evaluated on the formalin-induced paw chronic inflammation in mice after oral administration. Mice were subaponeurotically injected in the left hind paw with 0.02 ml of 3.75% formalin, then subjected to 500, 250 and 125 mg/kg of DHU001 oral administration, once a day for 10 days during which then the hind-paw thickness and volume were measured daily. The paw wet-weight, histological profiles, histomorphometrical analyses and paw tumor necrosis factor (TNF)-${\alpha}$ contents were conducted at termination. After two formalin treatments, a marked increase in the paw thickness and volume was detected in the formalin-injected control as compared with that in the intact control, plus at the time of sacrifice the paw wet-weights, paw TNF-${\alpha}$ contents were also dramatically increased with severe chronic inflammation signs at histopathological observations. However, these formalin-induced chronic inflammatory changes were dramatically decreased by treatment of dexamethasone and all three different dosages of DHU001. DHU001 has favorable effects on formalin-induced chronic inflammation mediated by TNF-${\alpha}$ suppression, and DHU001 may represent an alternative approach for the treatment of chronic inflammatory diseases.