Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation

Vascular calcification, a pathologic response to defective calcium and phosphate homeostasis, is strongly associated with cardiovascular mortality and morbidity. In this study, we have observed that pyruvate dehydrogenase kinase 4 (PDK4) is upregulated and pyruvate dehydrogenase complex phosphorylation is increased in calcifying vascular smooth muscle cells (VSMCs) and in calcified vessels of patients with atherosclerosis, suggesting that PDK4 plays an important role in vascular calcification. Both genetic and pharmacological inhibition of PDK4 ameliorated the calcification in phosphate-treated VSMCs and aortic rings and in vitamin D3-treated mice. PDK4 augmented the osteogenic differentiation of VSMCs by phosphorylating SMAD1/5/8 via direct interaction, which enhances BMP2 signaling. Furthermore, increased expression of PDK4 in phosphate-treated VSMCs induced mitochondrial dysfunction followed by apoptosis. Taken together, our results show that upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification

The genome sequence of Xanthomonas oryzae pathovar oryzae KACC10331, the bacterial blight pathogen of rice

The nucleotide sequence was determined for the genome of Xanthomonas oryzae pathovar oryzae (Xoo) KACC10331, a bacterium that causes bacterial blight in rice (Oryza sativa L.). The genome is comprised of a single, 4 941 439 bp, circular chromosome that is G + C rich (63.7%). The genome includes 4637 open reading frames (ORFs) of which 3340 (72.0%) could be assigned putative function. Orthologs for 80% of the predicted Xoo genes were found in the previously reported X.axonopodis pv. citri (Xac) and X.campestris pv. campestris (Xcc) genomes, but 245 genes apparently specific to Xoo were identified. Xoo genes likely to be associated with pathogenesis include eight with similarity to Xanthomonas avirulence (avr) genes, a set of hypersensitive reaction and pathogenicity (hrp) genes, genes for exopolysaccharide production, and genes encoding extracellular plant cell wall-degrading enzymes. The presence of these genes provides insights into the interactions of this pathogen with its gramineous host

Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with liver cirrhosis: a retrospective multicenter study

Background/AimsThis study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC).MethodsWe retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010.ResultsOf the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047).ConclusionsBRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO

Selective Removal of Water Generated during Hydrogenotrophic Methanation from Culture Medium Using Membrane Distillation

Methane production was carried out in two different types of reactors using a thermophilic and hydrogenotrophic methanogen, Methanothermobacter sp. KEPCO-1, which converts hydrogen and carbon dioxide into methane at 60 °C. The two reactors used for methane production were stirred-tank reactor (ST) and a bubble column reactor (BC), which were selected because they can provide a good comparison between the medium agitation type and gas–liquid mass transfer. The specific growth rate of KEPCO-1 in the ST and BC was 0.03 h−1 and 0.07 h−1, respectively. The methane conversion rate increased to 77.8 L/L/d in the ST and 19.8 L/L/d in the BC. To prevent the dilution of nutrients in the medium by the water generated during the hydrogenotrophic methanation reaction, a membrane distillation (MD) process was applied to selectively remove water from the culture medium. The MD process selectively removed only water from the medium. Fouling by KEPCO-1 had a negligible effect on flux and showed a high removal performance flux of 16.3 ± 3.1 L/m2/h. By operating the MD process in conjunction with the hydrogenotrophic methanation process, it is possible to prevent the dilution of the nutrients in the medium by the water generated during the methanation process, thereby maintaining stable microbial growth and methanation activity

Protective Effect of <i>Lonicera japonica</i> on PM_2.5-Induced Pulmonary Damage in BALB/c Mice via the TGF-β and NF-κB Pathway

This study aimed to assess the protective effect of an extract of Lonicera japonica against particulate-matter (PM)2.5-induced pulmonary inflammation and fibrosis. The compounds with physiological activity were identified as shanzhiside, secologanoside, loganic acid, chlorogenic acid, secologanic acid, secoxyloganin, quercetin pentoside, and dicaffeoyl quinic acids (DCQA), including 3,4-DCQA, 3,5-DCQA, 4,5-DCQA, and 1,4-DCQA using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The extract of Lonicera japonica reduced cell death, reactive oxygen species (ROS) production, and inflammation in A549 cells. The extract of Lonicera japonica decreased serum T cells, including CD4+ T cells, CD8+ T cells, and total T helper 2 (Th2) cells, and immunoglobulins, including immunoglobulin G (IgG) and immunoglobulin E (IgE), in PM2.5-induced BALB/c mice. The extract of Lonicera japonica protected the pulmonary antioxidant system by regulating superoxide dismutase (SOD) activity, reduced glutathione (GSH) contents, and malondialdehyde (MDA) levels. In addition, it ameliorated mitochondrial function by regulating the production of ROS, mitochondrial membrane potential (MMP), and ATP contents. Moreover, the extract of Lonicera japonica exhibited a protective activity of apoptosis, fibrosis, and matrix metalloproteinases (MMPs) via TGF-β and NF-κB signaling pathways in lung tissues. This study suggests that the extract of Lonicera japonica might be a potential material to improve PM2.5-induced pulmonary inflammation, apoptosis, and fibrosis

Anti-Amnesia-like Effect of <i>Pinus densiflora</i> Extract by Improving Apoptosis and Neuroinflammation on Trimethyltin-Induced ICR Mice

This study was conducted to investigate the anti-amnestic property of Korean red pine bark extract (KRPBE) on TMT-induced cognitive decline in ICR mice. As a result of looking at behavioral function, the consumption of KRPBE improved the spatial work ability, short-term learning, and memory ability by Y-maze, passive avoidance, and Morris water maze tests. KRPBE suppressed antioxidant system damage by assessing the SOD activity, reduced GSH content, and MDA levels in brain tissue. In addition, it had a protective effect on cholinergic and synaptic systems by regulating ACh levels, AChE activity, and protein expression levels of ChAT, AChE, SYP, and PSD-95. Also, the KRPBE ameliorated TMT-induced mitochondrial damage by regulating the ROS content, MMP, and ATP levels. Treatment with KRPBE suppressed Aβ accumulation and phosphorylation of tau and reduced the expression level of BAX/BCl-2 ratio and caspase 3, improving oxidative stress-induced apoptosis. Moreover, treatment with KRPBE improved cognitive dysfunction by regulating the neuro-inflammatory protein expression levels of p-JNK, p-Akt, p-IκB-α, COX-2, and IL-1β. Based on these results, the extract of Korean red pine bark, which is discarded as a byproduct of forestry, might be used as an eco-friendly material for functional foods or pharmaceuticals by having an anti-amnesia effect on cognitive impairment

<i>Codium fragile</i> Suppresses PM_2.5-Induced Cognitive Dysfunction by Regulating Gut–Brain Axis via TLR-4/MyD88 Pathway

This study was conducted to evaluate the cognitive dysfunction improvement effect of aqueous extract of Codium fragile (AECF) by regulating the imbalance of the gut–brain axis in chronic particulate matter (PM)2.5-exposed mice. The physiological compounds of AECF were identified as hexadecanamide, oleamide, octadecanamide, stearidonic acid, and linolenic acid by the ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC Q-TOF MSE) analysis. To evaluate the effect of PM2.5 on the antioxidant system, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, and malondialdehyde (MDA) contents were measured in colon and brain tissues. AECF significantly ameliorated the imbalance of the antioxidant systems. Also, AECF improved intestinal myeloperoxidase (MPO) activity, the abundance of the gut microbiome, short-chain fatty acids (SCFAs) contents, and tight junction protein expression against PM2.5-induced damage. In addition, AECF prevented PM2.5-induced inflammatory and apoptotic expression via the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88) pathway in colon and brain tissues. Additionally, AECF enhanced the mitochondrial function, including the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) contents in brain tissues. Furthermore, AECF regulated the cholinergic system, such as acetylcholine (ACh) contents, acetylcholinesterase (AChE) activity, and protein expression levels of AChE and choline acetyltransferase (ChAT) in brain tissues. To evaluate the effect of cognitive dysfunction caused by PM2.5-induced intestinal dysfunction, behavior tests such as Y-maze, passive avoidance, and Morris water maze tests were performed. From the results of the behavior tests, AECF ameliorated spatial learning and memory, short-term memory, and long-term learning and memory function. This study confirmed that AECF reduced PM2.5-induced cognitive dysfunction by regulating gut microbiome and inflammation, apoptosis, and mitochondrial function by enhancing the gut–brain axis. Based on these results, this study suggests that AECF, which contains fatty acid amides, might be a potential material for ameliorating PM2.5-induced cognitive dysfunction via gut–brain axis improvement

<i>Codium fragile</i> Suppressed Chronic PM_2.5-Exposed Pulmonary Dysfunction via TLR/TGF-β Pathway in BALB/c Mice

This study investigated the ameliorating effect of the aqueous extract of Codium fragile on PM2.5-induced pulmonary dysfunction. The major compounds of Codium fragile were identified as palmitic acid, stearic acid, and oleamide using GC/MS2 and hexadecanamide, oleamide, and 13-docosenamide using UPLC-Q-TOF/MSE. Codium fragile improved pulmonary antioxidant system deficit by regulating SOD activities and reducing GSH levels and MDA contents. It suppressed pulmonary mitochondrial dysfunction by regulating ROS contents and mitochondrial membrane potential levels. It regulated the inflammatory protein levels of TLR4, MyD88, p-JNK, p-NF-κB, iNOS, Caspase-1, TNF-α, and IL-1β. In addition, it improved the apoptotic protein expression of BCl-2, BAX, and Caspase-3 and attenuated the fibrous protein expression of TGF-β1, p-Smad-2, p-Smad-3, MMP-1, and MMP-2. In conclusion, this study suggests that Codium fragile might be a potential material for functional food or pharmaceuticals to improve lung damage by regulating oxidative stress inflammation, cytotoxicity, and fibrosis via the TLR/TGF-β1 signaling pathway