Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We ...investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1.
A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks.
When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks.
RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1
, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks
. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.
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.
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).
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.
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.
Wild ginseng is known to contain additional physiologically and pharmacologically active substances than common ginseng. The utilization of this herb can be maximized by altering its composition via ...tissue culture generating adventitious roots. We enriched the content of specific ginsenosides and investigated their role in ameliorating memory impairment. Cultured wild ginseng root was subjected to extraction, steaming, and fermentation using
to enhance the levels of ginsenosides Rg5 /Rk1. The analysis of product, HLJG0701, confirmed target ginsenosides. We analyzed the inhibitory effect of ginsenoside Rg5/Rk1, HLJG0701 and the raw material on acetylcholinesterase. Further, we performed Morris water maze, Y-maze, and passive avoidance tasks with mice exhibiting memory deficit induced by scopolamine, and we analyzed the concentrations of acetylcholinesterase and acetylcholine in their brains. Studies showed that the levels of ginsenosides Rg5 /Rk1, not found in the raw material, were enhanced in HLJG0701. Ginsenosides and HLJG0701 significantly inhibited acetylcholinesterase unlike the raw material. In all behavioral tasks, HLJG0701 showed memory improvement. It reduced acetylcholinesterase, whereas, it preserved acetylcholine in brain. In conclusion, cultured wild ginseng root extract fermented by
contains the distinctive ginsenosides Rg5/Rk1, which may ameliorate memory impairment via inhibition of acetylcholinesterase resulting in increased acetylcholine levels in the brain.
Climate change has increased variable weather patterns that affect plants. To address these issues, we developed a microbial biocontrol agent against drought stress in kimchi cabbage (
L. subsp.
). ...We selected three bacterial strains (
sp. CS9,
TSJ7, and
TT41) because they showed a survival rate of up to 50% and good growth rate when treated with 30% PEG 6000. The three strains were treated with kimchi cabbage to confirm their enhanced drought stress resistance under non-watering conditions. Among the three strains, the TT41 treated group showed a significant increase in various plant parameters compared with the negative control on the 7th day. We performed extensive profiling of primary and secondary metabolites from kimchi cabbage and the TT41 strain. Multivariate and pathway analyses revealed that only the TT41 group clustered with the well-watered group and showed almost the same metabolome on the 7th day. When treated with TT41, lactic acid was identified as an indicator metabolite that significantly improved drought stress tolerance. Furthermore, lactic acid treatment effectively induced drought stress tolerance in kimchi cabbage, similar to that achieved with the TT41 strain.
Radiation-induced intestinal toxicity is common among cancer patients after radiotherapy. Endothelial cell dysfunction is believed to be a critical contributor to radiation tissue injury in the ...intestine. Geranylgeranylacetone (GGA) has been used to treat peptic ulcers and gastritis. However, the protective capacity of GGA against radiation-induced intestinal injury has not been addressed. Therefore, we investigated whether GGA affects intestinal damage in mice and vascular endothelial cell damage in vitro. GGA treatment significantly ameliorated intestinal injury, as evident by intestinal crypt survival, villi length and the subsequently prolonged survival time of irradiated mice. In addition, intestinal microvessels were also significantly preserved in GGA-treated mice. To clarify the effect of GGA on endothelial cell survival, we examined endothelial function by evaluating cell proliferation, tube formation, wound healing, invasion and migration in the presence or absence of GGA after irradiation. Our findings showed that GGA plays a role in maintaining vascular cell function; however, it does not protect against radiation-induced vascular cell death. GGA promoted endothelial function during radiation injury by preventing the loss of VEGF/VEGFR1/eNOS signaling and by down-regulating TNFα expression in endothelial cells. This finding indicates the potential impact of GGA as a therapeutic agent in mitigating radiation-induced intestinal damage.
Background and ObjectivesCurrently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and ...differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. Methods and ResultsIn our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. ConclusionsOur study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.
Cephalotocin is a bioactivity-regulating peptide expressed in octopus (
Octopus vulgaris
). The peptide sequence of cephalotocin is very similar to the peptide sequence of mammalian vasopressin, and ...cephalotocin has been proposed to mainly activate arginine vasopressin 1b receptor (Avpr1b) in the brain. However, the effects of cephalotocin on mammalian behavior have not been studied. In the current study, cephalotocin significantly reduced both the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from not only cultured neuronal cells from postnatal Sprague–Dawley (SD) rats but also hippocampal slices from 4-week-old male C57BL/6 mice. Intraperitoneal (IP) injection did not affect the open field behaviors of C57BL/6 mice. Cephalotocin was directly infused into the hippocampus because the normalized Avpr1b staining intensity divided by the DAPI staining intensity indicated that Avpr1b expression tended to be high in the hippocampus. A hippocampal infusion of 1 mg/kg cephalotocin via an implanted cannula exerted an anti-stress effect, significantly reducing the immobility time in the tail suspension test (TST). The present results provide evidence that the effects of cephalotocin on the activity of hippocampal neurons are related to ameliorating stress, suggesting that cephalotocin may be developed as an anti-stress biomodulator that functions by affecting the brain.
Objective. We aimed to determine whether elevated levels of various inflammatory and immune proteins in umbilical cord blood are associated with an increased risk of newborn hearing screening (NHS) ...test failure in preterm neonates. Methods. This retrospective cohort study included 127 premature singleton infants who were born at ≤33.6 weeks. Umbilical cord plasma at birth was assayed for interleukin (IL)-6, complement C3a and C5a, matrix metalloproteinase (MMP)-9, macrophage colony-stimulating factor (M-CSF), and endostatin levels using ELISA kits. Neonatal blood C-reactive protein (CRP) levels were measured within 2 hours of birth. The primary outcome measure was a uni- or bilateral refer result on an NHS test. Univariate and multivariate analyses were applied. Results. Fifteen (11.8%) infants failed the NHS test. In the univariate analyses, high IL-6 and low C3a levels in umbilical cord plasma, funisitis, and an elevated CRP level (>5 mg/L) in the immediate postnatal period were significantly associated with NHS test failure. However, the levels of umbilical cord plasma MMP-9, C5a, M-CSF, and endostatin were not significantly different between infants who passed and those who failed the NHS test. Multiple logistic regression analyses indicated that elevated umbilical cord plasma C3a levels were independently associated with a reduced risk of NHS test failure, whereas elevated levels of umbilical cord plasma IL-6 and high CRP levels in the immediate postnatal period were significantly associated with NHS test failure. Conclusions. Our data demonstrated that in preterm neonates, a systemic fetal inflammatory response reflected by umbilical cord plasma IL-6 and immediate postnatal CRP levels may contribute to the risk for NHS test failure, whereas the changes in complement activation fragments initiated in utero may have protective effect of hearing screen failure.
The purpose of this study is to monitor the pesticide residues in frozen fruits and vegetables distributed and sold in online and offline markets in Korea. For the study, 107 samples of 34 types of ...frozen fruits and vegetables were examined, and a total of 341 pesticide residues were analyzed by using multiclass pesticide multi-residue methods of the Korean Food Code. As a result, pesticide residues were detected from 16 of 64 frozen fruits samples and 15 of 43 frozen vegetables samples. Conclusively, residues were detected from 31 samples in total, showing a detection rate of 29.0%. Specifically, pyridaben exceeded the Maximum Residue Limits (MRLs) based on the Positive list system (PLS) in one of the frozen radish leaves, and the violation rate was 0.9%. Detection on frozen fruits and vegetables was made 23 times for 11 types and 36 times for 21 types. In total, 28 types of pesticide residues were detected 59 times. Fungicides were detected the most in frozen fruits, while insecticides were detected the most in frozen vegetables. The most detected pesticides were the insecticide, acaricide chlorfenapyr (5) and the fungicide boscalid (5). Chlorfenapyr was detected only in frozen vegetables, and boscalid was detected in frozen fruits except one. 본 연구에서는 냉동 과·채류의 잔류농약 실태조사를 위해 국내 온·오프라인 매장에서 유통 및 판매 중인 냉동 과·채류 107건을 대상으로 하여 다종농약다성분 분석법으로 잔류농약 341종을 분석하였다. 잔류농약 분석 결과 냉동 과일류 64건에서 16건, 냉동 채소류 43건에서 15건이 검출되어, 총 31건에서 잔류농약이 검출되었으며, 검출률 29.0%를 보였다. 이 중 냉동무청 1건에서 pyridaben이 PLS (positive list system)에 따라 농약 잔류허용기준을 초과하였으며, 부적합률은 0.9%로 나타났다. 냉동 과일류와 냉동 채소류 중 잔류농약은 각각 11종 23회, 21종 36회 검출되어, 총 28종 59회 검출되었다. 냉동 과일류에선 살균제가 7종 17회로 가장 많이 검출되었고, 냉동 과·채류에선 14종 26회로 살충제가 가장 많이 검출되었다. 최다 검출 농약은 살충제 및 살비제인 chlorfenapyr (5회)와 살균제인 boscalid (5회)로, chlorfenapyr는 냉동 채소류에서만 검출되었고, boscalid는 1건을 제외하고 모두 냉동 과일류에서 검출되었다. 본 연구 결과로 냉동과·채류에 다양한 종류의 농약이 잔류하고 있음을 확인하였으며, 향후 냉동 과·채류에 대한 잔류농약 안전성 관리를 위한 기초자료로 사용될 수 있을 것으로 판단된다.
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