Temporary postoperative myocardial injury and long-term survival in liver transplant patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is increasing worldwide due to the aging population and cardiometabolic syndrome. However, the extent of postoperative myocardial injury, the most common cause of death during the 30 days after noncardiac surgery, remains unclear with respect to liver transplant (LT) patients with CAD. We examined the link between post-LT high sensitivity cardiac troponin I (hs_cTnI) and long-term survival according to liver disease severity. METHODS: Consecutive patients who underwent LT (n = 3,220) from 2010 to 2020 were evaluated retrospectively. CAD was defined as a history of coronary artery bypass surgery or percutaneous intervention, or previous myocardial infarction. Peak hs_cTnI levels within 30 days post-transplant were compared in patients with and without CAD. The primary endpoint was defined as an all-cause mortality at 12 years following LT. Secondary endpoints include peak hs_cTnI level within post-transplant 30 days and 30-day mortality. Survival analysis was performed using the Kaplan-Meier method. RESULTS: CAD patients (n = 264, 8.2%) had higher peak hs_cTnI levels within 30 days post-LT than those without CAD (median [interquartile]: 0.068 [0.030-0.154] vs. 0.087 [0.037-0.203] ng/ml, respectively; P = 0.004); however, the mortality rate was comparable (14.7% vs. 14.8%, respectively, P = 0.999), at 12 years, and 1.9% vs. 1.1% (P = 0.522) at 30 days, respectively, at 30 days. Subgroup analysis with stratified liver disease severity identified a similar risk of long-term mortality. CONCLUSIONS: Although the peak hs_cTnI level within 30 days was higher in revascularized or treated CAD patients after LT compared those without CAD, long-term mortality rates at 12 years and 30-day mortality rate were comparable.

C-reactive protein-to-albumin ratio is a predictor of 1-year mortality following liver transplantation.

BACKGROUND: Considering the importance of the inflammatory status of recipients on outcomes following liver transplantation (LT), we investigated the association between C-reactive protein-to-albumin ratio (CAR) and one-year mortality following LT and compared it with other parameters reflecting patients' underlying inflammatory status. METHODS: A total of 3,614 consecutive adult LT recipients were retrospectively evaluated. Prognostic parameters were analyzed using area under the receiver operating characteristic curve (AUROC) analysis, and subsequent cutoffs were derived. For survival analysis, Cox proportional hazards and Kaplan-Meier analyses were performed. RESULTS: The AUROC for CAR to predict one-year mortality after LT was 0.68 (0.65-0.72), which was the highest compared with other inflammatory parameters, with the best cutoff of 0.34. A CAR ≥ 0.34 was associated with a significantly higher one-year mortality rate (13.3% vs. 5.8 %, log-rank P < 0.001) and overall mortality rate (24.5% vs. 12.9%, log-rank P = 0.039). A CAR ≥ 0.34 was an independent predictor of one-year mortality (hazard ratio, 1.40 [1.03-1.90], P = 0.031) and overall mortality (hazard ratio 1.39 [1.13-1.71], P = 0.002) after multivariable adjustment. CONCLUSIONS: Preoperative CAR (≥ 0.34) was independently associated with a higher risk of one-year and overall mortality after LT. This may suggest that CAR, a simple and readily available biomarker, maybe a practical index that may assist in the risk stratification of liver transplantation outcomes.

Global biosphere primary productivity changes during the past eight glacial cycles.

Global biosphere productivity is the largest uptake flux of atmospheric carbon dioxide (CO2), and it plays an important role in past and future carbon cycles. However, global estimation of biosphere productivity remains a challenge. Using the ancient air enclosed in polar ice cores, we present the first 800,000-year record of triple isotopic ratios of atmospheric oxygen, which reflects past global biosphere productivity. We observe that global biosphere productivity in the past eight glacial intervals was lower than that in the preindustrial era and that, in most cases, it starts to increase millennia before deglaciations. Both variations occur concomitantly with CO2 changes, implying a dominant control of CO2 on global biosphere productivity that supports a pervasive negative feedback under the glacial climate.

KHG21834 attenuates glutamate-induced mitochondrial damage, apoptosis, and NLRP3 inflammasome activation in SH-SY5Y human neuroblastoma cells.

New compounds were screened to develop effective drugs against glutamate-induced toxicity. The present study assessed the effects of the novel thiazole derivative KHG21834 against glutamate-induced toxicity in human neuroblastoma SH-SY5Y cell cultures. Treatment of SH-SY5Y cells with KHG21834 significantly protected cells against glutamate-induced toxicity in a dose-dependent manner, with an optimum concentration of 50 µM. KHG21834 protected SH-SY5Y cells against glutamate toxicity by suppressing glutamate-induced oxidative stress by 50%. KHG21834 also attenuated glutamate-induced mitochondrial membrane potential, ATP level reductions, and intracellular Ca2+ influx. Furthermore, KHG21834 efficiently reduced glutamate-induced ER stress and NLRP3 inflammasome activation (59% and 65% of glutamate group, respectively). In addition, KHG21834 effectively attenuated glutamate-induced levels of Bax, Bcl-2, cleaved caspase-3, p-p38, p-JNK proteins, and TUNEL positive cells. To our knowledge, this is the first study showing that KHG21834 can effectively protect SH-SY5Y cells against glutamate toxicity, suggesting that this compound may be a valuable therapeutic agent for the treatment of glutamate toxicity.

Protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride on hypoxia-induced ß-amyloid production in SH-SY5Y cells.

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer's disease (AD), the molecular mechanism that determines the relationship between hypoxiainduced ß-amyloid (Aß) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced Aß production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin E2, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced Aß production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity. [BMB Reports 2019; 52(7): 439-444].

3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates MPP＋-induced cytotoxicity by regulating oxidative stress and mitochondrial dysfunction in SH-SY5Y cells.

Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4- phenylpyridinium (MPP＋)-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against MPP＋-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated MPP＋-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of MPP＋-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, Ca2＋, and ATP in MPP＋-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against MPP＋-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin. [BMB Reports 2018; 51(11): 590-595].

High-Precision Measurement of N2O Concentration in Ice Cores.

Atmospheric nitrous oxide (N2O) is a greenhouse gas and ozone-depleting substance whose emissions are substantially perturbed by current human activities. Although air trapped in polar ice cores can provide direct information about N2O evolution, analytical precision was not previously sufficient for high temporal resolution studies. In this work, we present a highly improved analytical technique with which to study N2O concentrations in ancient-air-trapped ice cores. We adopt a melt-refreezing method to extract air and use a gas chromatography-electron capture detector (GC-ECD) to determine N2O concentrations. The GC conditions are optimized to improve the sensitivity for detecting N2O. Retrapped N2O in ice during the extraction procedure is precisely analyzed and corrected. We confirmed our results using data from the Styx Glacier ice core in Antarctica by comparing them with the results of a dry-extraction method. The precision estimated from the pooled standard deviation of replicated measurements of the Styx ice core was 1.5 ppb for ∼20 g of ice, a smaller sample of ice than was used in previous studies, showing a significant improvement in precision. Our preliminary results from the Styx Glacier ice core samples have the potential to define small N2O variations (a few parts per billion) at centennial time scales.

Variations in bacterial and archaeal communities along depth profiles of Alaskan soil cores.

Understating the microbial communities and ecological processes that influence their structure in permafrost soils is crucial for predicting the consequences of climate change. In this study we investigated the bacterial and archaeal communities along depth profiles of four soil cores collected across Alaska. The bacterial and archaeal diversity (amplicon sequencing) overall decreased along the soil depth but the depth-wise pattern of their abundances (qPCR) varied by sites. The community structure of bacteria and archaea displayed site-specific pattern, with a greater role of soil geochemical characteristics rather than soil depth. In particular, we found significant positive correlations between methane trapped in cores and relative abundance of methanogenic archaeal genera, indicating a strong association between microbial activity and methane production in subsurface soils. We observed that bacterial phylogenetic community assembly tended to be more clustered in surface soils than in deeper soils. Analyses of phylogenetic community turnover among depth profiles across cores indicated that the relative influence of deterministic and stochastic processes was mainly determined by soil properties rather than depth. Overall, our findings emphasize that the vertical distributions of bacterial and archaeal communities in permafrost soils are to a large extent determined by the variation in site-specific soil properties.

3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates NLRP3 inflammasome-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglial cells.

The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation. This study investigated the effects of KHG26792 on the inflammasome-mediated signaling pathway in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. KHG26792 significantly attenuated several inflammatory responses including tumor necrosis factor-α, interleukin-1ß, interleukin-6, reactive oxygen species, and mitochondrial potential in these cells. KHG26792 also suppressed LPS-induced increase NLRP3, activated caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) levels. Furthermore, KHG26792 successfully blocked LPS-activated adenosine triphosphate (ATP) level, likely through the purinergic receptor P2X ligand-gated ion channel 7 (P2X7) receptor. Our results suggest that the anti-inflammatory functions of KHG26792 may be, at least in part, due to regulation of the P2X7R/NLRP3-mediated signaling pathway during microglial activation.

Effect of Inductively Coupled Plasma on the Structural and Electrical Properties of Ti-Doped ITO Films Formed by IPVD.

In this study, we investigated Ti-doped ITO films formed through ionized physical vapor deposition (IPVD) using inductively coupled plasma (ICP). Ti-doped ITO thin films showed an enhanced mobility with ICP power; owing to the improved crystallinity, and the sheet resistance of the Ti-doped ITO (30 nm) largely decreased from 295.1 to 134.5 ohm/sq, even during at room temperature. Therefore, IPVD technology offers a useful tool for transparent electrodes with a large area window-unified touch-screen panel.

A comparison study between periosteum and resorbable collagen membrane on iliac block bone graft resorption in the rabbit calvarium.

BACKGROUND: To compare the different resorption patterns between resorbable membrane barrier and periosteum after iliac block bone grafting radiographically and histologically. METHODS: Eighteen mature male rabbits weighing from 2.0 to 2.5 kg were used. The recipient site was the rabbit skull, and autogenous iliac bone was used as the grafting material. The harvested iliac block bones were divided in the following groups: autogenous iliac block bone with preservation of the periosteum (the periosteum group), autogenous iliac block bone covered with a resorbable collagen membrane (Biomesh®, Samyang Co, Korea) after removing the periosteum (the collagen membrane group), and autogenous iliac block bones with removal of the periosteum (the control group). In each experimental group, periosteum or resorbable collagen membrane of the donor site was fixed directed to the periosteum of the recipient site. The specimens were examined macroscopically, radiographically, histologically, and histomorphometrically at every 2, 4, and 8 weeks. RESULTS: All groups presented excellent bone graft healing state without inflammation, dehiscence, or displacement. The radiolucency increased from mild to moderate in all groups over the experiment. The mean thickness of the upper end of the cortical iliac bone graft was statistically significantly different between the control group and the periosteum group, between the four-week and eight-week control group, and between the four- week and eight-week periosteum group (p & 0.05). CONCLUSION: This study suggests that both the periosteum and the resorbable collagen membrane may help to prevent soft tissue infiltration into the bone graft and to reduce bone graft resorption compared to block graft alone.