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Ho Jung Jeong,1,* Hyun Lee,1,* Keumhee C Carriere,2,3 Jung Hoon Kim,1 Jin-Hyung Han,1 Beomsu Shin,1 Byeong-Ho Jeong,1 Won-Jung Koh,1 O Jung Kwon,1 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea; 2Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB, Canada; 3Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, South Korea *These authors contributed equally to this work Purpose: The association between positive bronchodilator response (BDR) at baseline and the effect of long-term bronchodilator therapy has not been well elucidated in patients with bronchiectasis. The aims of our study were to explore the association between positive BDR at baseline and lung-function improvement following long-term (3–12 months) bronchodilator therapy in bronchiectasis patients with airflow limitation. Materials and methods: The medical records of 166 patients with clinically stable bronchiectasis who underwent baseline pre- and postbronchodilator spirometry and repeated spirometry after 3–12 months of bronchodilator therapy were retrospectively reviewed. For analysis, patients were divided into two groups, responders and poor responders, based on achievement of at least 12% and 200 mL in forced expiratory volume in 1 second (FEV1) following bronchodilator therapy from baseline FEV1. Results: A total of 57 patients (34.3%) were responders. These patients were more likely to have positive BDR at baseline than poor responders (38.6% [22 of 57] vs 18.3% [20 of 109], P=0.004). This association persisted after adjustment for other confounding factors (adjusted odds ratio 2.298, P=0.034). However, we found FEV1 improved significantly following long-term bronchodilator therapy, even in patients without positive BDR at baseline (change in FEV1 130 mL, interquartile range -10 to 250 mL; P

Hyeong Jin Lee,1,* Bongjin Lee,2,* June Dong Park,2 Hyung Joo Jeong,2 Yu Hyeon Choi,2 Hee Young Ju,1 Che Ry Hong,1 Ji Won Lee,1 Hyery Kim,1 Dong In Suh,3 Kyung Duk Park,1 Hyoung Jin Kang,1 Hee Young Shin,1 Hyo Seop Ahn1 1Department of Pediatrics, Cancer Research Institute, 2Division of Pediatric Intensive Care, Department of Pediatrics, 3Division of Pulmonology, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea *These authors contributed equally to this work Purpose: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.Materials and methods: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP) measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥20%) drops.Results: Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0–160.33 mmHg] versus 105 [59.8–148.3 mmHg]; P

Chang-Moon Lee,1 Tai Kyoung Lee,2–5 Dae-Ik Kim,1,6 Yu-Ri Kim,7 Meyoung-Kon Kim,7 Hwan-Jeong Jeong,2–5 Myung-Hee Sohn,2–5 Seok Tae Lim2–5 1Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 2Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 3Cyclotron Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 4Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 6School of Electrical, Electronic Communication, and Computer Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 7Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seounbuk-Gu, Seoul, Republic of Korea Purpose: In this study, we investigated the absorption and distribution of rhodamine B isothiocyanate (RITC)-incorporated silica oxide nanoparticles(SiNPs) (RITC-SiNPs) after oral exposure, by conducting optical imaging, with a focus on tracking the movement of RITC-SiNPs of different particle size and surface charge. Methods: RITC-SiNPs (20 or 100 nm; positively or negatively charged) were used to avoid the dissociation of a fluorescent dye from nanoparticles via spontaneous or enzyme-catalyzed reactions in vivo. The changes in the nanoparticle sizes and shapes were investigated in an HCl solution for 6 hours. RITC-SiNPs were orally administered to healthy nude mice at a dose of 100 mg/kg. Optical imaging studies were performed at 2, 4, and 6 hours after oral administration. The mice were sacrificed at 2, 4, 6, and 10 hours post-administration, and ex vivo imaging studies were performed. Results: The RITC-SiNPs were stable in the HCl solution for 6 hours, without dissociation of RITC from the nanoparticles and without changes in size and shape. RITC-SiNPs flowed into the small intestine from the stomach and gradually moved along the gut during the experiment. In the ex vivo imaging studies, optical signals were observed mostly in the lungs, liver, pancreas, and kidneys. The orally administered RITC-SiNPs, which were absorbed in the systemic circulation, were eliminated from the body into the urine. The 20 nm RITC-SiNPs showed higher uptake in the lungs than the 100 nm RITC-SiNPs. The distribution of the 100 nm RITC-SiNPs in the liver was higher than that of the 20 nm RITC-SiNPs, but the differences in the surface charge behavior were imperceptible. Conclusion: We demonstrated that the movement of RITC-SiNPs after oral exposure could be traced by optical imaging. Optical imaging has the potential to provide valuable information that will help in understanding the behavior of SiNPs in the body following exposure. Keywords: silica nanoparticles, oral exposure, rhodamine B isothiocyanate, RITC-SiNP

Chang-Moon Lee,1–4,* Hwan-Jeong Jeong,1–4,* Kuk-No Yun,1–3 Dong Wook Kim,1–4 Myung-Hee Sohn,1–4 Jong Kwon Lee,5 Jayoung Jeong,5 Seok Tae Lim1–4 *These authors contributed equally to this work.1Department of Nuclear Medicine; 2Cyclotron Research Center; 3Research Institute of Clinical Medicine; 4Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Osong-Eup, Chungchungbuk-Do, Republic of KoreaBackground: Understanding how nanomaterials are distributed in the body after exposure is important for assessing whether they are safe. In this study, we investigated the behavior and accumulation of nanoscaled and submicron-scaled zinc oxide (ZnO) particles in the body using optical imaging following oral exposure.Methods: To trace these nanoparticles in the body, ZnO nanoparticles were conjugated with a monoreactive hydroxysuccinimide ester of Cy5.5 (Cy5.5-NHS), and the conjugation-stabilizing effect of Cy5.5 on the nanoparticles was evaluated in simulated gastric fluid (pH 1.2) for 7 hours. To compare the distribution of Cy5.5-NHS and Cy5.5-conjugated ZnO nanoparticles, Cy5.5-NHS 0.5 mg/kg and Cy5.5-conjugated ZnO nanoparticles 250 mg/kg were administered orally to healthy rats. We collected blood from the rats at predesignated time points for 7 hours after administration, and optical imaging studies were performed at 1, 2, 3, 5, and 7 hours after dosing. To investigate the extent of nanoparticle accumulation in the organs and tissues, the mice were sacrificed at 23 hours after administration, and the organs were removed and imaged.Results: Cy5.5-conjugated ZnO nanoparticles were stable in simulated gastric fluid for 7 hours. The signal intensity of Cy5.5-NHS in blood was highest 3 hours after oral administration, and Cy5.5-conjugated ZnO nanoparticles showed the highest signal intensity in blood 5–7 hours after administration. In vivo optical images indicated that Cy5.5-NHS showed optical signals in the lung, liver, and gastrointestinal tract after oral administration, whereas Cy5.5-conjugated ZnO nanoparticles were seen only in the gastrointestinal tract. Seven hours following administration, biodistribution studies demonstrated that Cy5.5-NHS accumulated in the lung and liver, and Cy5.5-conjugated ZnO nanoparticles resulted in a strong signal in the kidney and liver. Different-sized ZnO nanoparticles showed dissimilar patterns of biodistribution in ex vivo optical images.Conclusion: ZnO nanoparticles are absorbed into the tissues following oral exposure and their behavior can be monitored and evaluated using optical imaging.Keywords: zinc oxide nanoparticles, biodistribution, optical imaging, oral administration

Background: Curcumin, the active ingredient of turmeric (Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases. Methods: Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3β]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3β, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion. Results: Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3β, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3β induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3β compared with the control. Conclusions: Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3β, and attenuation of p38 and JNK. [ABSTRACT FROM AUTHOR]

Background and Purpose: 5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT(1A) spinally-mediated analgesia, the role of other 5-HT(1) receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT(1) agonists, including sumatriptan, on acute pain, plus their effect on afferent-evoked synaptic transmission onto superficial dorsal horn neurons.Experimental Approach: For in vivo experiments, 5-HT agonists were injected via chronically implanted spinal catheters to examine their effects in acute mechanical and thermal pain assays using a paw pressure analgesymeter and a Hargreave's device. For in vitro experiments, whole-cell patch-clamp recordings of primary afferent-evoked glutamatergic EPSC were made from lamina II neurons in rat lumbar spinal slices.Key Results: Intrathecal (i.t.) delivery of the 5-HT(1A) agonist R ± 8-OH-DPAT (30-300 nmol) produced a dose-dependent thermal, but not mechanical, analgesia. Sumatriptan and the 5-HT(1B), 5-HT(1D), 5-HT(1F) agonists CP93129, PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R ± 8-OH-DPAT (1 µM) and sumatriptan (3 µM) both reduced the amplitude of the evoked EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3-3 µM) had no effect on the evoked EPSC. The actions of both R ± 8-OH-DPAT and sumatriptan were abolished by the 5-HT(1A) antagonist WAY100635 (3 µM).Conclusions and Implications: These findings indicate that the 5-HT(1A) receptor subtype predominantly mediates the acute antinociceptive and cellular actions of 5-HT(1) ligands within the rat superficial dorsal horn. [ABSTRACT FROM AUTHOR]

Intact immunoglobulin G antibody has a relatively large molecule size of approximately 150 kDa that remains in the bloodstream for many weeks, which is a considerable disadvantage when it is used to carry radioactive materials for imaging. To lower background activity and increase the contrast of images, we investigated antivascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) conjugated dextran for VEGF receptor 2 imaging in tumor xenografted mice. DTPA-conjugated aminodextran was synthesized, reacted with sulfo-LC-SPDP, and then reacted with DC101. The binding affinity of DTPA-dextran-DC101 to Flk-1 was measured. The gamma imaging and biodistributions of (99m)Tc-DTPA-dextran-DC101, (99m)Tc-DTPA-DC101, and (125)I-DC101 were studied in B16F10 melanoma xenografted mice. The dissociation values for DC101, DTPA-DC101, and DTPA-dextran-DC101 were 22.48, 3.05, and 14.74 pM, respectively. In gamma images, (99m)Tc-DTPA-dextran-DC101 showed weak liver uptake and rapid kidney elimination. In biodistribution results, the liver uptake of (99m)Tc-DTPA-dextran-DC101 was similar with that of (99m)Tc-DTPA-DC101 at each time point. However, the blood activity of (99m)Tc-DTPA-dextran-DC101 has shown significant differences, compared with (99m)Tc-DTPA-DC101 at all time points. The tumor accumulation of dextran-conjugated antibody was increased with time, whereas that of dextran nonconjugated antibody decreased. In particular, the pattern of tumor uptake of (99m)Tc-DTPA-dextran-DC101 was similar to that of (125)I-DC101, so this was thought to reflect the kinetics of DC101, unlike the nonconjugated form. The results of this study suggested that introduction of dextran moiety to make (99m)Tc-radiolabeled DC101 imaging agent could provide better images with the impaired background and the steady increasing binding to the receptor. However, further studies are necessary to improve clinical pharmacokinetics, such as enhancement of tumor uptake and impaired renal uptake. [ABSTRACT FROM AUTHOR]

Abstract: Kim DS, Sim Y-J, Jeong HJ, Kim GC. Effect of active resistive exercise on breast cancer–related lymphedema: a randomized controlled trial. Objective: To investigate the differences between the effects of complex decongestive physiotherapy with and without active resistive exercise for the treatment of patients with breast cancer–related lymphedema (BCRL). Design: Randomized control-group study. Setting: An outpatient rehabilitation clinic. Participants: Patients (N=40) with diagnosed BCRL. Interventions: Patients were randomly assigned to either the active resistive exercise group or the nonactive resistive exercise group. In the active resistive exercise group, after complex decongestive physiotherapy, active resistive exercise was performed for 15min/d, 5 days a week for 8 weeks. The nonactive resistive exercise group performed only complex decongestive physiotherapy. Main Outcome Measures: The circumferences of the upper limbs (proximal, distal, and total) for the volume changes, and the Short Form-36 version 2 questionnaire for the quality of life (QOL) at pretreatment and 8 weeks posttreatment for each patient. Results: The volume of the proximal part of the arm was significantly more reduced in the active resistive exercise group than that of the nonactive resistive exercise group (P<.05). In the active resistive exercise group, there was significantly more improvement in physical health and general health, as compared with that of the nonactive resistive exercise group (P<.05). Conclusions: For the treatment of patients with BCRL, active resistive exercise with complex decongestive physiotherapy did not cause additional swelling, and it significantly reduced proximal arm volume and helped improve QOL. [ABSTRACT FROM AUTHOR]

This study evaluated the safety and volume reduction of ultrasonography (US)-guided radiofrequency ablation (RFA) for benign thyroid nodules, and the factors affecting the results obtained. A total of 302 benign thyroid nodules in 236 euthyroid patients underwent RFA between June 2002 and January 2005. RFA was carried out using an internally cooled electrode under local anesthesia. The volume-reduction ratio (VRR) was assessed by US and safety was determined by observing the complications during the follow-up period (1-41 months). The correlation between the VRR and several factors (patient age, volume and composition of the index nodule) was evaluated. The volume of index nodules was 0.11-95.61 ml (mean, 6.13 +/- 9.59 ml). After ablation, the volume of index nodules decreased to 0.00-26.07 ml (mean, 1.12 +/- 2.92 ml) and the VRR was 12.52-100% (mean, 84.11 +/- 14.93%) at the last follow-up. A VRR greater than 50% was observed in 91.06% of nodules, and 27.81% of index nodules disappeared. The complications encountered were pain, hematoma and transient voice changes. In conclusion, RFA is a safe modality effective at reducing volume in benign thyroid nodules. [ABSTRACT FROM AUTHOR]

The effect of Haeamtang (HAT) on the colon cancer HT-29 cells was investigated in this study. A water extract of HAT significantly decreased the number of HT-29 cells in a dose-and time-dependent manner as determined by a MTT assay. Flow cytometry results revealed a dose- and time-dependent increase of dead cells in HT-29 cells treated with HAT extract. The anticancer activity of the H AT extract is attributed to apoptosis induced in HT-29 cells, which was demonstrated by increased caspase-3 activity and poly-ADP-ribose polymerase fragmentation. A selective caspase inhibitor, z-VAD-fmk, inhibited the HAT-induced cell death. Taken together, these results demonstrate that HAT extract induces apoptosis in HT-29 cells. [ABSTRACT FROM AUTHOR]

Aims: Age-related frailty and reduced physical activity contribute to a degenerative loss of muscle mass, function, and strength, which is known as sarcopenia. Increasing evidence has shown that vitamin D has beneficial effects on the muscle health. However, the molecular mechanisms of vitamin D have not been fully elucidated. In this study, we aimed to demonstrate whether vitamin D can overcome muscle atrophy due to aging, especially with respect to the regulation of myokines., Main Methods: Young (3-month-old) and aged (18-month-old) C57BL/6 mice were assigned to the following 3 groups: normal diet (1000 IU/kg), vitamin D 3 -supplemented diet (20,000 IU/kg), and normal diet plus exercise for 4 months., Key Findings: We found that the reduction in muscle strength and mass due to aging was reversed by vitamin D 3 supplementation. The levels of markers involved in muscle atrophy and cellular senescence in the muscle of the aged mice were substantially decreased by vitamin D 3 . Interestingly, we observed that the expression of apelin and its receptor (APJ), which is known to be secreted after exercise, significantly increased in aged muscles with a vitamin D 3 -supplemented diet but not in the young mice. Moreover, circulating interleukin-6 (IL-6) and growth differentiation factor 8 (GDF8) levels were significantly increased in the aged mice but were restored by vitamin D 3 treatment., Significance: Our present data indicate that vitamin D 3 supplementation ameliorates aging-induced muscle atrophy and senescence, similar to the effects of exercise, suggesting the positive impact of vitamin D as an intervention strategy to prevent aging-induced metabolic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study assessed the performance of the Allplex TM stx1/2/2a/2d Typing (ASTXT) assay (Seegene) for diagnosis and typing Shiga toxin-producing Escherichia coli. Analytical sensitivity and specificity were evaluated using 18 spiked strains, and cross-reactivity was tested on 114 strains including E. coli without Shiga toxin. Clinical performance was evaluated using the proficiency panels and 76 stool samples. Analytical sensitivity was revealed to 4.14 log 10 CFU ml -1 for E. coli strain with stx1, 4.47 log 10 CFU ml -1 for strain with stx2, 4.03 log 10 CFU ml -1 for strain with stx2a, and 4.02 log 10 CFU ml -1 for strain with stx2d, respectively. Imprecisions were within 5 % and cross-reactivity was not observed. The ASTXT assay showed perfect agreement with the proficiency panel results and achieved 100 % positive and negative percent agreement using clinical stool samples. The ASTXT assay demonstrated reliable performance for the rapid detection and typing of Shiga toxin-producing E. coli in human stool samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Metformin (MetF) is used worldwide as a first-line therapy for type 2 diabetes. Recently, interest in the pleiotropic effects of MetF, such as its anticancer and antiaging properties, has increased. However, the molecular target of MetF and the detailed mechanism underlying its ability to inhibit cell growth through autophagy induction remain incompletely understood. In this study, using an innovative label-free drug affinity responsive target stability (DARTS)-LC-MS/MS method, we discovered that mitochondrial voltage-dependent anion channel 1 (VDAC1) is a novel binding protein involved in the induction of autophagy-related cell death by high-dose MetF in hepatocellular carcinoma (HCC). Computational alanine scanning mutagenesis revealed that MetF and VDAC1 (D9, E203) interact electrostatically. MetF disrupts the IP 3 R-GRP75-VDAC1 complex, which plays a key role in stabilizing mitochondria-associated ER membranes (MAMs), by binding to VDAC1. This disruption leads to increased cytosolic calcium levels, thereby contributing to autophagy induction. MetF also decreased the AMP/ATP ratio and activated the AMPK pathway. Cells with genetic knockdown of VDAC1 mimicked the activity of MetF. In conclusion, this study provides new insights into the involvement of MetF in ionic interactions with VDAC1, contributing to its anticancer effects in HCC. These findings help elucidate the diverse biological and pharmacological effects of MetF, particularly its influence on autophagy, as well as the potential of MetF as a therapeutic agent for diseases characterized by VDAC1 overexpression., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Cancer cells secrete extracellular vesicles (EV) encapsulating bioactive cargoes to facilitate inter-organ communication in vivo and are emerging as critical mediators of tumor progression and metastasis, a condition which is often accompanied by a dysregulated cholesterol metabolism. Whether EVs are involved in the control of cholesterol homeostasis during tumor metastasis is still undefined and warrant further investigation. Here, we find that breast cancer-derived exosomal miR-9-5p induces the expression of HMGCR and CH25H, two enzymes involved in cholesterol synthesis and the conversion of 25-hydroxycholesterol from cholesterol by targeting INSIG1, INSIG2 and ATF3 genes in the liver. Notably, in vivo miR-9-5p antagomir treatment and genetic CH25H ablation prevents tumor metastasis in a mouse model of breast cancer. Thus, our findings reveal the regulatory mechanism of tumor-derived miR-9-5p in liver metastasis by linking oxysterol metabolism and Kupffer cell polarization, shedding light on future applications for cancer diagnosis and treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)