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Bacterial infection of the uterus in Hanwoo can kill embryos. Therefore, many antibiotics have been used to treat this infection in the uterus of repeat breeders. Incorrect use of antibiotics has led to resistance in bacteria. Natural compounds have used as substitutes for antibiotics because they are safe and have very mild side effects. This study was conducted to examine the antimicrobial effects of five extracts from medicinal plants including Humulus japonicas (Hj), Phelledendron amurense (Pa), Viola mandshurica (Vm), Carthamus tinctorius (Ct), and Chelidoni herba (Ch) on bacteria isolated from the uterus of Hanwoo using the paper disc diffusion method. Hj and Pa extracts had potent antimicrobial effects against Staphylococcus lentus, Streptococcus infantarius subsp. coli, and Bacillus pumilus. Pa had the greatest antimicrobial effect among the five medicinal plants and was effective against 19 types of bacteria from bovine uterus. Compared to Pa, Hj showed weaker antimicrobial effects on all the bacteria tested except Pseudomonas aeruginosa. Vm, Ct, and Ch also showed weak antimicrobial effects on the tested bacteria. The results obtained suggest that Hj and Pa are natural compounds suitable for treating bacterial infection in repeat breeders and improving conception rates of Hanwoo. [ABSTRACT FROM AUTHOR]

Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-pcoumaroyl β -D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-1β and TNF-α. In addition, CG significantly suppressed LPS-induced degradation of IκB. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and antiinflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells. [ABSTRACT FROM AUTHOR]

Background: The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk. We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC. Methods: Outpatients with COPD were enrolled from January to June in 2012. The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively. Additionally, correlations between mMRC scores and each item of CAT scores were analyzed. Results: Classification of 257 patients using the CAT score vs mMRC scale was as follows. By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D. On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D. The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510. The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001). Conclusions: The classification of COPD produced by the mMRC or CAT score was not identical. Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the differences in clinical characteristics and treatment outcomes between older and younger tuberculosis (TB) patients in Korea. Methods: We retrospectively analyzed the medical records of 271 younger (20-64 years old at diagnosis) and 199 older (=65 years) TB patients who had been newly diagnosed and treated at Chonnam National University Hospital from May 2008 to August 2010. Results: Dyspnea and comorbid medical conditions were more frequent and positive TB culture rates were higher in older TB patients. In chest computed tomography (CT) scans of pulmonary TB patients, older patients were less likely to have micronodules (<7 mm in diameter), nodules (<30 mm in diameter), masses (>30 mm in diameter), and cavities compared with younger patients, but were more likely to have consolidations. Incidence of adverse drug reactions did not differ between the two groups, except for severe gastrointestinal disorders. There were no significant differences in favorable treatment outcomes between younger and older TB patients (97% vs. 94%, respectively; p = 0.251). Conclusions: Older TB patients had more frequent dyspnea and less frequent active TB findings on chest CT. Treatment success and adverse drug reaction rates were similar in older and younger TB patients. [ABSTRACT FROM AUTHOR]

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as neuronal protection against excitotoxicity and anti-inflammatory property, the biological activity of 3,4,5-trihydroxycinnamic acid (THC), a derivative of hydroxycinnamic acids, has not been clearly examined. The objective of the present study is to evaluate the anti-inflammatory effects of THC on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. THC significantly suppressed LPS-induced excessive production of nitric oxide (NO) and expression of iNOS, which is responsible for the production of iNOS. THC also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1βand TNF-α in BV2 microgilal cells. Furthermore, THC significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm. Therefore, THC attenuated nuclear translocation of NF-κB, a major pro-inflammatory transcription factor. Taken together, the present study for the first time demonstrates that THC exhibits antiinflammatory activity through the suppression of NF-κB transcriptional activation in LPS-stimulated BV2 microglial cells. [ABSTRACT FROM AUTHOR]

Purpose: Little information exists regarding the association of specific cytokine levels and different subgroups of patients with critical illness-related corticosteroid insufficiency (CIRCI). Methods: Data from a previous prospective study on adrenal function in the ICU were used in this study. CIRCI was diagnosed when either the basal cortisol was less than 10 μg/ml or the Δ cortisol was less than 9 μg/ml. The patients with CIRCI were further divided into a low basal cortisol (LBC) group (basal cortisol <10 μg/ml), and low Δ cortisol (LDC) group (basal cortisol ≥ 10 μg/ml and Δ cortisol <9 μg/ml). Serum cytokine levels were compared among the normal (NOM), LBC, and LDC groups. Results: The serum of 82 out of 123 (67%) patients included in the previous study was available for analysis; these patients were included in the present study. The overall incidence of CIRCI was 43.9% (36 out of 82 patients). Among patients with CIRCI, 16 (44.4%) were classified as the LBC group and 20 (55.6%) as the LDC group. The LDC group had significantly higher levels of IL-6 and IL-10 compared to both the NOM and LBC groups ( p < 0.01). The LDC group also had significantly increased TNF-α ( p = 0.002) compared to the LBC group. There were no significant differences in any of the cytokine levels between the NOM and LBC groups. Conclusions: Elevated cytokines were associated with adrenal dysfunction in a subset of patients meeting the criteria for CIRCI (normal or high basal cortisol and low Δ cortisol). [ABSTRACT FROM AUTHOR]

Background. Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. Methods. This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. Results. Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index ⩾18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of 14 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. Conclusions. Early aggressive treatment comprising at least <4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are intracellular pathogens that elicit a specific T-cell response characterized by the production of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-12. However, little information exists regarding the levels of specific cytokines in patients with NTM lung disease. Therefore, we compared cytokine production in peripheral blood mononuclear cells (PBMCs) from patients with NTM lung disease with that in PBMCs from healthy controls. Pro- and anti-inflammatory cytokine production was measured by enzyme-linked immunosorbent assay in the PBMCs of 29 patients with NTM lung disease and 15 healthy controls. Phytohemagglutinin (PHA)-induced IFN-γ production and lipopolysaccharide (LPS)-induced production of TNF-α and IL-12p40 were significantly lower in the PBMCs of patients with NTM lung disease than in those of the healthy controls. The production of these cytokines did not differ significantly between patients infected with Mycobacterium avium complex (MAC) and those infected with Mycobacterium abscessus; however, IL-10 production was lower in patients infected with M. abscessus than in those infected with MAC. Decreased IFN-γ, TNF-α, and IL-12 production may be associated with host susceptibility to the development of MAC and M. abscessus lung disease. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to examine the risk of using drug-induced hepatotoxicity (DIH) than control subjects in treating tuberculosis (TB) in hepatitis C virus (HCV)-seropositive patients. The study confirmed that treatment for TB in HCV-seropositive patients could be acted on the regular manner, using standard short-course regimens, with the condition that monthly liver function tests are cautiously executed.

Panax ginseng is one of the most highly valued herbal medicines in the Orient, where it has gained an almost magical reputation for being able to maintain the quality of life. The root of ginseng contains noble tetracyclic triterpenenoid saponins, which are thought to be the major effective ingredients in P. ginseng. The first committed step in ginsenoside synthesis is the cyclization of 2,3-oxidosqualene to dammarenediol II by oxidosqualene cyclase, dammarenediol synthase (DDS). The gene encoding DDS has been characterized. Here, we investigated the expression of the DDS gene together with the genes involved in ginsenoside biosynthesis (SS, SE, PNX, PNY, PNY2 and PNZ). Expression of DDS mRNA was higher in flower buds compared with root, leaf and petiole of ginseng plants. Elicitor (methyl jasmonate) treatment up-regulated the expression of DDS mRNA. Ectopic expression of DDS in a yeast mutant (erg7) lacking lanosterol synthase resulted in the production of dammarenediol and hydroxydammarenone which were confirmed by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). RNA interference (RNAi) of DDS in transgenic P. ginseng resulted in silencing of DDS expression which leads to a reduction of ginsenoside production to 84.5% in roots. These results indicate that expression of DDS played a vital role in the biosynthesis of ginsenosides in P. ginseng. [ABSTRACT FROM PUBLISHER]

We report the successful preparation of gold nanoparticles (Au NPs) using a novel electroreduction process, which is simple, fast, and environmentally friendly (toxic chemicals such as strong reducing agents are not required). Our process allows for the mass production of Au NPs and adequate particle size control. The Au NPs prepared show high biocompatibility and are non-toxic to healthy human cells. By applying radiofrequency (RF) ablation, we monitored the electro-hyperthermia effect of the Au NPs at different RFs. The Au NPs exhibit a fast increase in temperature to 55 °C within 5 min during the application of an RF of 13 MHz. This temperature rise is sufficient to promote apoptosis through thermal stress. Our work suggests that the selective Au NP-mediated electro-hyperthermia therapy for tumor cells under an RF of 13 MHz has great potential as a clinical treatment for specific tumor ablation. [ABSTRACT FROM AUTHOR]

COVID-19 can lead to pulmonary complications, including organizing pneumonia. Steroids are essential in treating post-COVID-19 organizing pneumonia. However, research on the clinical benefits of initiating steroid treatment early for this condition is limited. To investigate the steroid initiation time in its association with treatment duration and corticosteroid dose for treating post-COVID-19 organizing pneumonia, we analyzed the data of 91 patients with post-COVID-19 organizing pneumonia at Chonnam National University Hospital between October 2020 and December 2022. Patients were categorized into early and late groups based on time from COVID-19 diagnosis to steroid initiation time for organizing pneumonia. The mean time interval between COVID-19 infection and steroid initiation time for treating organizing pneumonia, was 18.4±8.6 days. Within the early treatment group (treatment initiated <18.4 days after COVID-19), which included 55 patients, the mean duration of steroid treatment was 43.1±18.3days. In contrast, the late treatment group (initiated ≥18.4 days after COVID-19), which consisted of 36 patients, had a longer mean duration of steroid treatment 59.1±22.6 days) (p<0.01). Regarding corticosteroid dosing, the early treatment group had an average dosage of 0.5±0.3 mg/kg/day, in contrast to the late group, which averaged 0.8±0.3 mg/kg/day (p<0.01). Regression analysis showed steroid initiation time significantly influenced treatment duration (β=0.80, p<0.01) and dosage (β=0.03, p<0.01). The clinical benefits of early steroid treatment for post-COVID-19 organizing pneumonia may lie in its association with reduced steroid treatment duration and dosage. [ABSTRACT FROM AUTHOR]

Abstract In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1–2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.

Mahonia napaulensis DC. has historically been used for traditional medicine in Vietnam. However, the biological mechanisms underlying its medicinal effects are not yet fully understood. In the present study, a crude extract derived from the M. napaulensis stem was fractionated with n-hexane, ethyl acetate (EtOAc), and water-saturated butanol (BuOH). The antioxidant activities of the crude extract and the fractionated samples were evaluated using a DPPH assay and a reducing power assay. Our results revealed that the EtOAc fraction showed the highest total phenolic content as well as the highest free radical scavenging activity and reducing power. The antiproliferative effects of M. napaulensis DC. extracts were detected using a MTT assay. The results showed a significant reduction in cell viability of over 70% in human colon carcinoma CoLo 205 cells at the highest concentration tested (200 µg/ml). We also used quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure the expression of mRNA transcripts involved in the regulation of cell proliferation such as survivin, p53, caspase-3, and caspase-9 in CoLo 205 cells treated with the crude extract and fractions to better understand the changes induced by the BuOH fraction. Two alkaloid compounds that possess strong antiproliferative activities in colon cancer cells, berberine and palmatine, were isolated from the BuOH fraction. The results from this study indicate that M. napaulensis may be considered a medicinal plant due to its anti-oxidative and antiproliferative properties. [ABSTRACT FROM AUTHOR]

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) represents a major public health concern, with an ongoing need for new effective treatments. Bedaquiline is an oral diarylquinoline that has shown encouraging treatment success and culture conversion rates in MDR-TB. Methods A South Korean patient registry was set up across 19 centres between 2016 and 2018 for the prospective collection of data from patients with MDR-TB who received either a bedaquiline-containing or a non-bedaquiline-containing regimen. Treatment was at the physician’s discretion (bedaquiline use requiring approval by special committee) and was based on patient characteristics, disease status, and local treatment guidelines. Results The safety population included 172 patients (88 bedaquiline and 84 non-bedaquiline). The mean (standard deviation, SD) duration of follow-up was 24.3 (9.5) months. Mean (SD) durations of treatment were 5.4 (1.8) months in bedaquiline-treated patients and 15.7 (6.7) months in the non-bedaquiline group. Treatment success (cured and treatment completed according to WHO 2013 treatment outcome definitions) was achieved by 56.3% of bedaquiline-treated and 45.2% of non-bedaquiline-treated patients. Sputum culture conversion rates were 90.4% and 83.7% with and without bedaquiline, respectively. Diarrhoea and nausea were the most frequently reported treatment-emergent adverse events (TEAEs) in the bedaquiline group (27.3% [24/88] and 22.7% [20/88], respectively). The most frequent bedaquiline-related TEAEs were prolonged QT interval (10.2%; 9/88), and diarrhoea and nausea (9.1% each; 8/88). QT interval prolongation was reported in 19.3% (17/88) of bedaquiline-treated and 2.4% (2/84) of non-bedaquiline-treated patients, but bedaquiline was not discontinued for any patient for this reason. There were 13 (14.7%) and three (3.6%) deaths in the bedaquiline-treated and non-bedaquiline groups, respectively. Review of fatal cases revealed no unexpected safety findings, and no deaths were bedaquiline-related. The most common cause of death was worsening cancer (three patients). Patients in the bedaquiline group tended to have poorer baseline risk profiles than non-bedaquiline patients and were more likely to have relapsed or already failed second-line treatment. Interpretation of mortality data was complicated by high rates of loss to follow-up in both groups. Conclusions The South Korean registry findings support previous risk/benefit observations and the continued use of bedaquiline as part of combination therapy in patients with MDR-TB.

Abstract Background The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted. Methods This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited. Discussion This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB. Trial registration ClinicalTrials.gov NCT04485156 . Registered on July 24, 2020.

Anti-inflammatory effects of caffeic acid derivatives have been widely reported. However, the effect of caffeic acid methyl ester (CAME) on the anti-allergic effect in mast cells has not been elucidated. The present study was aimed to investigate the anti-allergic properties of CAME and its underlying mechanism. Rat basophilic leukemia (RBL-2H3) cells were incubated withphorbol-12-myristate-13-acetate (PMA) and a calcium ionophore, A23187 to induce mast cell activation. Anti-allergic effect of CAME was examined by measuring cytokine, histamine and β-hexosaminidase release. Western blotting was conducted to determine cyclooxygenase-2 (COX-2) expression, Mitogen-activated protein kinases (MAPKs) activation and nuclear factor-κB (NF-κB) translocation. CAME significantly suppressed PMA/A23187-induced TNF-α secretion, and β-hexosaminidase and histamine release in a concentration-dependent manner. Furthermore, CAME significantly attenuated PMA/A23187-induced COX-2 expression and nuclear translocation of NF-κB. CAME significantly suppressed PMA/A23187-induced increased phosphorylation of p38, ERK and JNK RBL-2H3 cells. The results demonstrate that CAME significantly attenuates anti-allergic action by suppressing degranulation of mast cells through the suppression of MAPKs/NF-κB signaling pathway in RBL-2H3 cells.

Background Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea. Methods A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement). Results The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers. Conclusion Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Abstract Pinosylvin stilbenes are phenolic compounds mainly occurring in the Pinaceae family. We previously reported that the accumulation of two pinosylvin stilbene compounds, dihydropinosylvin methyl ether (DPME) and pinosylvin monomethyl ether (PME), in Pinus strobus trees was highly enhanced by infection with pine wood nematodes (PWNs: Bursaphelenchus xylophilus), and these two compounds showed strong nematicidal activity against PWNs. In this work, we established a system of pinosylvin stilbene (DPME and PME) production via the in vitro culture of P. strobus calli, and we examined the nematicidal activity of callus extracts. Calli were induced from the culture of mature zygotic embryos of P. strobus. Optimized growth of calli was obtained in 1/2 Litvay medium with 1.0 mg/L 2,4-D and 0.5 mg/L BA. DPME and PME accumulation did not occur in nonaged (one-month-old) calli but increased greatly with prolonged callus culture. The concentrations of DPME and PME in three-month-old dark-brown calli were 6.4 mg/g DW and 0.28 mg/g DW, respectively. The effect of methyl jasmonate treatment on the accumulation of DPME and PME was evaluated in cell suspension culture of P. strobus. However, the treatment appeared to show slight increase of DPME accumulation compared to callus browning. A test solution prepared from crude ethanol extracts from aged calli (three months old) containing 120 µg/ml DPME and 5.16 µg/ml PME treated with PWNs resulted in 100% immobilization of the adult PWNs and 66.7% immobilization of the juvenile PWNs within 24 h. However, nonaged callus extracts did not show any nematicidal activity against juvenile PWNs and showed less than 20% nematicidal activity against adult PWNs. These results indicate that pinosylvin stilbenes can be effectively produced by prolonged culture of P. strobus calli, can be isolated using simple ethanolic extraction, and are applicable as beneficial eco-friendly compounds with nematicidal activity against PWNs.

BackgroundHyperuricemia is common during tuberculosis (TB) treatment, especially in association with pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment.MethodsWe conducted a single-center retrospective cohort study. From January 2010 through June 2017, we assessed all consecutive TB patients at Chonnam National University Hospital in South Korea. Hyperuricemia was defined as serum uric acid levels exceeding 7.0 mg/dL (men) and 6.0 mg/dL (women).ResultsOf the 1,143 patients included, PZA was administered to 1,081 (94.6%), and hyperuricemia was detected in 941 (82.3%). Eight patients experienced MACEs. Multivariate analysis using logistic regression indicated that prior ischemic heart disease was associated with MACE development (OR,14.087; 95% CI,3.304-60.061; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184-12.299; P = 0.703). For patients without drug-resistant TB, the absence of hyperuricemia was associated with higher mortality (OR, 2.609; 95% CI, 1.066-6.389; P = 0.036), whereas hyperuricemia was associated with less worse outcomes (OR,0.316; 95% CI,0.173-0.576; P < 0.000).ConclusionsAlthough most patients treated with PZA developed hyperuricemia, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to consistent adherence to TB treatment.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms, but can cause a chronic pulmonary infection in some patients. Therefore, there could be host factors susceptible to this disease. A structural lung disease including damages of lungs caused by previous respiratory infection has been suggested as a host factor. Here we presented a case of NTM pulmonary disease which developed in a structural lung disease caused by a rare congenital lung disease. A 46-year-old male, was transferred to our hospital with an unexpandable lung after a closed thoracostomy due to spontaneous pneumothorax. His chest computed tomography showed an absence of left pulmonary artery at the time of admission. Mycobacterial culture in sputum, bronchial washing fluid, and pleural fluid showed the growth of NTM. Mycobacterium intracellulare was isolated from all positive cultures in the specimens. Combinations of drugs for M. intracellulare pulmonary disease including azithromycin, rifampin, and ethambutol were administered for 16 months. Amikacin intra venous treatment used for 6 months after treatment initiation. Culture conversion was achieved at 4 months of treatment. There was no evidence of recurrence of NTM pulmonary disease for 6 months after treatment. In conclusion, patients who have structural lung disease need to be careful monitoring about development of NTM pulmonary disease.

Plasmodium vivax (P. vivax) is one of the human’s most common malaria parasites. P. vivax is exceedingly difficult to control and eliminate due to the existence of extravascular reservoirs and recurring infections from latent liver stages. Traditionally, licorice compounds have been widely investigated against viral and infectious diseases and exhibit some promising results to combat these diseases. In the present study, computational approaches are utilized to study the effect of licorice compounds against P. vivax Duffy binding protein (DBP) to inhibit the malarial invasion to human red blood cells (RBCs). The main focus is to block the DBP binding site to Duffy antigen receptor chemokines (DARC) of RBC to restrict the formation of the DBP–DARC complex. A molecular docking study was performed to analyze the interaction of licorice compounds with the DARC binding site of DBP. Furthermore, the triplicates of molecular dynamic simulation studies for 100 ns were carried out to study the stability of representative docked complexes. The leading compounds such as licochalcone A, echinatin, and licochalcone B manifest competitive results against DBP. The blockage of the active region of DBP resulting from these compounds was maintained throughout the triplicates of 100 ns molecular dynamic (MD) simulation, maintaining stable hydrogen bond formation with the active site residues of DBP. Therefore, the present study suggests that licorice compounds might be good candidates for novel agents against DBP-mediated RBC invasion of P. vivax.

Background The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). Methods The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected. Conclusion NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

ObjectiveIn-hospital tuberculosis (TB) transmission remains a concern. Airborne infection isolation (AII) can be discontinued in hospitalized patients with suspected active pulmonary TB when the results of three consecutive sputum acid-fast bacilli (AFB) smears are negative. However, fiberoptic bronchoscopy can be performed in patients who may have difficulty in producing sputum samples. This study aimed to investigate the usefulness of Mycobacterium tuberculosis-polymerase chain reaction (MTB-PCR) with bronchial washing specimens in predicting AII discontinuation in hospitalized patients with suspected active pulmonary TB.MethodsWe reviewed the medical charts of patients admitted to a tertiary hospital who were isolated and underwent fiberoptic bronchoscopy for suspicious pulmonary TB from January 2016 to December 2019. Patients with positive MTB-PCR results in the initial sputum examination were excluded. Criteria for discontinuing AII were defined as negative results for three consecutive AFB smears from respiratory specimens, or cases diagnosed other than TB. The study patients were divided into two groups: TB group and non-TB group.ResultsIn total, 166 patients were enrolled in the study. Of them, 35 patients were diagnosed with TB. There was no significant difference between the number of males in the TB (81; 61.8%) and non-TB (21; 60.0%) group. Though 139 patients had negative results on MTB-PCR using washing specimens, eight showed positive AFB culture. Of the 139 patients with negative MTB-PCR results, 138 had negative results for three consecutive AFB smears or were established to not have pulmonary TB. Therefore, the predictive accuracy of MTB-PCR with bronchial washing samples for discontinuing AII was 99.2%.ConclusionAlthough a negative result from MTB-PCR with bronchial washing samples cannot exclude pulmonary TB, it can predict AII discontinuation in hospitalized patients with suspected active pulmonary TB.

ObjectivePulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs.MethodsWe retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital.ResultsFifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038).ConclusionOlder age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.

Ewing sarcoma (ES) is a highly malignant carcinoma prevalent in children and most frequent in the second decade of life. It mostly occurs due to t(11;22) (q24;q12) translocation. This translocation encodes the oncogenic fusion protein EWS/FLI (Friend leukemia integration 1 transcription factor), which acts as an aberrant transcription factor to deregulate target genes essential for cancer. Traditionally, flavonoids from plants have been investigated against viral and cancerous diseases and have shown some promising results to combat these disorders. In the current study, representative flavonoid compounds from various subclasses are selected and used to disrupt the RNA-binding motif of EWS, which is required for EWS/FLI fusion. By blocking the RNA-binding motif of EWS, it might be possible to combat ES. Therefore, molecular docking experiments validated the binding interaction patterns and structural behaviors of screened flavonoid compounds within the active region of the Ewing sarcoma protein (EWS). Furthermore, pharmacogenomics analysis was used to investigate potential drug interactions with Ewing sarcoma-associated genes. Finally, molecular dynamics simulations were used to investigate the stability of the best selected docked complexes. Taken together, daidzein, kaempferol, and genistein exhibited a result comparable to ifosfamide in the proposed in silico study and can be further analyzed as possible candidate compounds in biological in vitro studies against ES.

Background/Aims Peripheral eosinophilia during tuberculosis (TB) treatment is common, but has not been fully evaluated. The aim of this study was to determine the prevalence and clinical significance of peripheral blood eosinophilia in patients undergoing anti-TB treatment. Methods We retrospectively reviewed the clinical and laboratory data of patients who received anti-TB treatment and had peripheral blood eosinophilia (> 5% of the total white blood cell count) at the Chonnam National University Hospital between January 2010 and December 2014. Results Of all 2,234 patients with TB who received anti-TB treatment, 397 (17.8%) had peripheral blood eosinophilia. Of the 397 with eosinophilia, we reviewed the data of 262 (66%), and cutaneous adverse drug reactions (CADRs) were observed in 161 (61.5%). Of the 161 with CADRs, itching (47.2%) and skin rash (47.8%) were common. Older age, abnormal liver function, and higher peak blood eosinophil percentage were associated with CADRs in multivariate analysis. There was a significant relationship between increased peak eosinophil counts and the degree of severity of CADRs. Conclusions Peripheral blood eosinophilia is a relatively common occurrence during anti-TB treatment. Peripheral blood eosinophil counts were higher according to the degree of severity of CADRs.

Background Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

ObjectivePneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.MethodsWe retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).ResultsThe IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).ConclusionsPatients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

ObjectiveThis study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs.MethodsWe retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs).ResultsTwenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543).ConclusionsMultiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

Objective Phellodendron amurense (P. amurense) and Humulus japonicus (H. japonicus) are closely involved in anti-oxidative response and increasing antioxidant enzymes activities. However, the effects of their extracts on development of preimplantation bovine embryos have not been investigated. Therefore, we investigated the effects of P. amurense and H. japonicus extracts on developmental competence and quality of preimplantation bovine embryos. Methods After in vitro fertilization, bovine embryos were cultured for 7 days in Charles Rosenkrans amino acid medium supplemented with P. amurense (0.01 μg/mL) and H. japonicus (0.01 μg/mL). The effect of this supplementation during in vitro culture on development competence and antioxidant was investigated. Results We observed that the blastocysts rate was significantly increased (p

ObjectivesArgon plasma coagulation (APC) is a noncontact form of electrocautery that utilizes ionized argon as the electrical current. A rigid bronchoscopic use of APC for the management of central airway obstruction could be safe and rapidly effective. This study evaluated the usefulness of rigid bronchoscopy with APC for the management of central airway obstructions due to benign or malignant tumors.MethodsTwenty patients with obstructing central airway tumors were retrospectively reviewed from February 2008 to February 2013 at Chonnam National University Hospital. All patients received rigid bronchoscopic tumor removal under general anesthesia. APC was applied before and after tumor removal.ResultsThe median age of patients was 59 years (interquartile range [IQR], 51 to 67 years) and 70% were female. The causes of airway obstruction included malignancy (n=8) and benign tumor (n=12). Airway tumors comprised intraluminal lesions (n=11, 55%) and mixed intraluminal/extraluminal lesions (n=9, 45%). The median tumor size was 15 mm (IQR, 10 to 18 mm). The median degree of airway obstruction was significantly reduced after intervention (90% [IQR, 88% to 96%] vs. 10% [IQR, 0% to 20%], P