Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from Korean Heart Rhythm Society Cryoablation registry.

BACKGROUND: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicenter registry of 12 tertiary hospitals, we analyzed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI<18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). RESULTS: A total of 2,648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups; 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. UW patients were the oldest, and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-year). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared to NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, p=0.02). Procedure-related complications occurred in 123 (4.7%) patients and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, p=0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: UW patients showed a higher risk of AF recurrence after cryoablation compared to NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Ginseng Berry Juice (GBJ) Regulates the Inflammation in Acute Ulcerative Mouse Models and the Major Bioactive Substances Are Ginsenosides Rb3, Rc, Rd, and Re.

Panax ginseng fruit is known to have various biological effects owing to its large amount of saponins such as ginsenosides. In the present study, ginseng berry juice was confirmed to be effective against acute inflammation. Ginseng berry juice was used for analysis of active constituents, antioxidant efficacy, and in vivo inflammation. A high-performance liquid chromatography method was used for analysis of ginsenosides. In an HCl/ethanol-induced acute gastric injury model, microscopic, immunofluorescent, and immunohistochemical techniques were used for analysis of inhibition of gastric injury and mechanism study. In a mouse model of acute gastritis induced with HCl/ethanol, ginseng berry juice (GBJ, 250 mg/kg) showed similar gastric injury inhibitory effects as cabbage water extract (CB, 500 mg/kg, P.O). GBJ dose-dependently modulated the pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-13 (IL-13). GBJ inhibited the activation of Nuclear Factor kappa bB (NF-κB) and suppressed the expressions of cyclooxigenase-2 (COX-2) and prostaglandin 2 (PGE2). The anti-inflammatory effect of GBJ is attributed to ginsenosides which have anti-inflammatory effects. Productivity as an effective food source for acute gastritis was analyzed and showed that GBJ was superior to CB. In addition, as a functional food for suppressing acute ulcerative symptoms, it was thought that the efficacy of gastric protection products would be higher if GBJ were produced in the form of juice rather than through various extraction methods.

Natural course of hemodynamically stable hemispheres contralateral to operated hemispheres in adult patients with ischemic moyamoya diseases.

The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up.

Anti-inflammatory potential via the MAPK signaling pathway of Lactobacillus spp. isolated from canine feces.

Two probiotic candidates, Lactobacillus reuteri C1 (C1) and Lactobacillus acidophilus C5 (C5), which were previously isolated from canines, were evaluated in the present study. L. reuteri and L. acidophilus have anti-oxidant, anti-inflammatory, immune-enhancing, and anti-cancer properties and exhibit various probiotic effects in humans and animals. The strains C1 and C5 demonstrated good tolerance to acid and bile salt exposure, exhibited effective adhesion to HT-29 cell monolayer, and displayed sensitivity to antibiotics, thus affirming their probiotic characteristics. Moreover, C1 and C5 exhibited the ability to downregulate the expression of inducible NO synthase (iNOS), an immunomodulatory factor, leading to a reduction in NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. These strains also demonstrated potent anti-inflammatory effects in LPS-stimulated RAW 264.7 cells, achieved through the augmentation of anti-inflammatory cytokine IL-10 expression and the inhibition of pro-inflammatory cytokine IL-1ß expression. These anti-inflammatory effects of C1 and C5 were closely associated with the mitogen-activated protein kinase (MAPK) signaling pathway. The results of the present study suggest that the C1 and C5 probiotic candidates attenuate LPS-induced inflammation via the MAPK signaling pathway and the strains can be used as probiotics considering their anti-inflammatory potential.

Production of fructooligosaccharide-containing bakery and sweet paste products using invertase.

This study investigated the production of bakery and sweet paste products containing the prebiotic fructooligosaccharide (FOS) using an in situ method with invertase. The FOS formation method was optimized for each product to ensure high quality and appropriate sweetness. The method effectively decreased the sugar content in the final product by 12.7-68.4% while maintaining quality. The FOS content was 3.8-4.8% in castella, 0.6-3.6% in sweet dough bread, and 7.5-8.5% in sweet chickpea paste. By contrast, the commercial method of adding FOS decreased product quality; castella product height decreased by 20.8%, and hardness increased by 79%. The specific volume of the sweet dough bread decreased by 17.4% and hardness increased by 59%. Therefore, we developed a commercially feasible method to efficiently utilize FOS in sugar-containing foods while maintaining their quality.

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation.

While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinson's disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using function magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examinations of cell-type specific STN feed-forward neural activity. Unilateral STN optogenetic stimulation elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, these manipulations effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetically induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS.

Distinct neurochemical influences on fMRI response polarity in the striatum.

The striatum, known as the input nucleus of the basal ganglia, is extensively studied for its diverse behavioral roles. However, the relationship between its neuronal and vascular activity, vital for interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within the striatum. Here, we demonstrate that optogenetic stimulation of dorsal striatal neurons or their afferents from various cortical and subcortical regions induces negative striatal fMRI responses in rats, manifesting as vasoconstriction. These responses occur even with heightened striatal neuronal activity, confirmed by electrophysiology and fiber-photometry. In parallel, midbrain dopaminergic neuron optogenetic modulation, coupled with electrochemical measurements, establishes a link between striatal vasodilation and dopamine release. Intriguingly, in vivo intra-striatal pharmacological manipulations during optogenetic stimulation highlight a critical role of opioidergic signaling in generating striatal vasoconstriction. This observation is substantiated by detecting striatal vasoconstriction in brain slices after synthetic opioid application. In humans, manipulations aimed at increasing striatal neuronal activity likewise elicit negative striatal fMRI responses. Our results emphasize the necessity of considering vasoactive neurotransmission alongside neuronal activity when interpreting fMRI signal.

The Hepatokine Orosomucoid 2 Mediates Beneficial Metabolic Effects of Bile Acids.

Bile acids (BAs) are pleiotropic regulators of metabolism. Elevated levels of hepatic and circulating BAs improve energy metabolism in peripheral organs, but the precise mechanisms underlying the metabolic benefits and harm still need to be fully understood. In the current study, we identified orosomucoid 2 (ORM2) as a liver-secreted hormone (i.e., hepatokine) induced by BAs and investigated its role in BA-induced metabolic improvements in mouse models of diet-induced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared with C57BL/6J control, partly due to the increased energy expenditure. However, when challenged with a HFD supplemented with cholic acid, Orm2-KO eliminated the antiobesity effect of BAs, indicating that ORM2 governs BA-induced metabolic improvements. Moreover, hepatic ORM2 overexpression partially replicated BA effects by enhancing insulin sensitivity. Mechanistically, ORM2 suppressed interferon-γ/STAT1 activities in inguinal white adipose tissue depots, forming the basis for anti-inflammatory effects of BAs and improving glucose homeostasis. In conclusion, our study provides new insights into the molecular mechanisms of BA-induced liver-adipose cross talk through ORM2 induction.

Association Between ECG Abnormalities and Mortality in a Low-Risk Population.

BACKGROUND: The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low-risk populations. To address this, we evaluated the association between ECG abnormality and mortality. METHODS AND RESULTS: We retrospectively assessed baseline ECG and all-cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check-ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All-cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow-up period of 8.8 years. Major ECG abnormalities were associated with all-cause mortality (hazard ratio [HR], 1.11 [95%, 1.03-1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63-2.27]) compared with no ECG abnormalities. All-cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1-4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1-2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15-2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05-4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26-1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02-1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15-9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33-4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35-2.19]), major Q-wave abnormality (HR, 1.6 [95% CI, 1.08-2.39]), and major ST-T abnormality (HR, 1.76 [95% CI, 1.01-3.04]). CONCLUSIONS: ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q-wave and ST-T abnormalities, were associated with cardiovascular mortality in a low-risk population.

Intrinsic Functional Connectivity between the Anterior Insular and Retrosplenial Cortex as a Moderator and Consequence of Cocaine Self-Administration in Rats.

While functional brain imaging studies in humans suggest that chronic cocaine use alters functional connectivity (FC) within and between key large-scale brain networks, including the default mode network (DMN), the salience network (SN), and the central executive network (CEN), cross-sectional studies in humans are challenging to obtain brain FC prior to cocaine use. Such information is critical to reveal the relationship between individual's brain FC and the subsequent development of cocaine dependence and brain changes during abstinence. Here, we performed a longitudinal study examining functional magnetic resonance imaging (fMRI) data in male rats (n = 7), acquired before cocaine self-administration (baseline), on 1 d of abstinence following 10 d of cocaine self-administration, and again after 30 d of experimenter-imposed abstinence. Using repeated-measures analysis of variance (ANOVA) with network-based statistics (NBS), significant connectivity changes were found between anterior insular cortex (AI) of the SN, retrosplenial cortex (RSC) of the DMN, somatosensory cortex, and caudate-putamen (CPu), with AI-RSC FC showing the most robust changes between baseline and 1 d of abstinence. Additionally, the level of escalated cocaine intake is associated with AI-RSC and AI-CPu FC changes between 1 d and 30 d of abstinence; further, the subjects' AI-RSC FC prior to cocaine intake is a significant moderator for the AI-RSC changes during abstinence. These results provide novel insights into the roles of AI-RSC FC before and after cocaine intake and suggest this circuit to be a potential target to modulate large-scale network and associated behavioral changes in cocaine use disorders.

Neovascularization in Outer Membrane of Chronic Subdural Hematoma : A Rationale for Middle Meningeal Artery Embolization.

OBJECTIVE: Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. METHODS: The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. RESULTS: The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. CONCLUSION: Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option.

Blood-brain barrier disruption imaging in postoperative cerebral hyperperfusion syndrome using DCE-MRI.

Little has been reported about the association between cerebral hyperperfusion syndrome (CHS) and blood-brain barrier (BBB) disruption in human. We aimed to investigate the changes in permeability after bypass surgery in cerebrovascular steno-occlusive diseases using dynamic contrast-enhanced MRI (DCE-MRI) and to demonstrate the association between CHS and BBB disruption. This retrospective study included 36 patients (21 hemispheres in 18 CHS patients and 20 hemispheres in 18 controls) who underwent combined bypass surgery for moyamoya and atherosclerotic steno-occlusive diseases. DCE-MRI and arterial spin labeling perfusion-weighted imaging (ASL-PWI) were obtained at the baseline, postoperative state, and discharge. Perfusion and permeability parameters were calculated at the MCA territory (CBF(territorial), Ktrans(territorial), Vp(territorial)) and focal perianastomotic area (CBF(focal), Ktrans(focal), Vp(focal)) of operated hemispheres. As compared with the baseline, both CBF(territorial) and CBF(focal) increased in the postoperative period and decreased at discharge, corresponding well to symptoms in the CHS group. Vp(focal) was lower in the postoperative period and at discharge, as compared with the baseline. In the control group, no parameters significantly differed among the three points. In conclusion, Vp at the focal perianastomotic area significantly decreased in patients with CHS during the postoperative period. BBB disruption may be implicated in the development of CHS after bypass surgery.

The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Clinical Outcome of Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage with Bundled Treatments: A Propensity Score-Matched Analysis.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as Hunt and Hess (HH) grades IV and V, is a challenging disease because of its high mortality and poor functional outcomes. The effectiveness of bundled treatments has been demonstrated in critical diseases. Therefore, poor-grade aSAH bundled treatments have been established. This study aims to evaluate whether bundled treatments can improve long-term outcomes and mortality in patients with poor-grade aSAH. METHODS: This is a comparative study using historical control from 2008 to 2022. Bundled treatments were introduced in 2017. We compared the rate of favorable outcomes (modified Rankin Scale score 0-2) at 6 months and mortality before and after the introduction of the bundled treatments. To eliminate confounding bias, the propensity score matching method was used. RESULTS: A total of 90 consecutive patients were evaluated. Forty-three patients received bundled treatments, and 47 patients received conventional care. The proportion of patients with HH grade V was higher in the bundle treatment group (41.9% vs. 27.7%). Conversely, the proportion of patients with fixed pupils on the initial examination was higher in the conventional group (30.2% vs. 38.3%). After 1:1 propensity score matching, 31 pairs were allocated to each group. The proportion of patients with 6-month favorable functional outcomes was significantly higher in the bundled treatments group (46.4% vs. 20.7%, p = 0.04). The 6-month mortality rate was 14.3% in the bundled treatments group and 27.3% in the conventional group (p = 0.01). Bundled treatments (odd ratio 14.6 [95% confidence interval 2.1-100.0], p < 0.01) and the presence of an initial pupil reflex (odd ratio 12.0 [95% confidence interval 1.4-104.6], p = 0.02) were significantly associated with a 6-month favorable functional outcome. CONCLUSIONS: The bundled treatments improve 6-month functional outcome and mortality in patients with poor-grade aSAH.

Effects of Acetaminophen on Reproductive Activities in Male Golden Hamsters.

Acetaminophen [Paracetamol, N-acetyl-para-aminophenol (APAP)] is a common over-the- counter analgesic agent as nonsteroidal anti-inflammatory drugs (NSAIDs). The high doses or the long-term treatment of acetaminophen via usual gavage feeding resulted in damage of testicles that presented recoverable impairment, as well as liver and kidney. The influence of acetaminophen was examined in male golden hamsters treated with acetaminophen- containing diet feeding. They were divided into 5 groups and subjected to this experiment for 4 weeks: animals housed in long photoperiod (LP) as LP control, animals housed in short photoperiod (SP) for 4 weeks as SP control (SP4), and groups of animals treated with low, middle, and high concentrations of acetaminophen (Low, Middle, High groups). Also animals housed in SP for 8 weeks were included (SP8) to contrast testicular activities, if necessary. As results, spermatozoa filled the seminiferous tubules of the testicles of animals in LP control and SP4 groups. The aspects were seen in the animals taken diets of low and middle doses of acetaminophen. The animals who fed high dose of acetaminophen showed large or small testicles. The large testicles displayed all germ cells at the steps of spermatogenesis. The small testicles presented no sperm as the animals housed in SP for 8 weeks. Thus these results indicate that acetaminophen invokes the antigonadal effects and accelerates the regressing process of the testicles in the animals compared to the animals exposed to SP.

Comparison of Office Blood Pressure, Automated Unattended Office Blood Pressure, Home Blood Pressure, and 24-Hour Ambulatory Blood Pressure Measurements.

BACKGROUND: Although previous studies have reported differences of blood pressure (BP) according to BP measurement methods, studies in Korean population were scarce. This study aimed to compare BP differences according to different BP measurement methods and assess hypertension phenotype. METHODS: This prospective study recruited 183 individuals (mean 55.9 years; 51.4% males). The BP measurements included office BP (auscultatory attended office BP [ausAOBP], automated attended office BP [aAOBP], and automated unattended office BP [aUAOBP]) and out-of-office BP (home BP [HBP] and ambulatory BP [ABP]) measurements taken within one week of each other. RESULTS: The mean systolic/diastolic BP differences between ausAOBP and other BPs according to different BP measurement methods were 3.5/2.3 mmHg for aAOBP; 6.1/2.9 mmHg for aUAOBP; 15.0/7.3 mmHg for daytime ABP; and 10.6/3.4 mmHg for average HBP. The increasing disparity between ausAOBP and other BPs in multivariable regression analysis was significantly associated with increasing BP. The prevalence of white-coat hypertension and masked hypertension in 107 individuals not taking antihypertensive medication was 25.4-26.8% and 30.6-33.3% based on ausAOBP, daytime ABP, and average HBP, respectively. The prevalence of white-coat uncontrolled hypertension and masked uncontrolled hypertension in 76 of those taking antihypertensive medication was 31.7-34.1% and 17.1-37.1%, respectively. CONCLUSION: This study showed a large disparity between office BP and out-of-office BP which became more pronounced when office BP by auscultation increased, suggesting that various BP measurement methods should be used to more accurately assess BP status.

Cyclophilin E (CypE) Functions as a Positive Regulator in Osteoblast Differentiation by Regulating the Transcriptional Activity of Runx2.

Cyclophilin E (CypE) belongs to the cyclophilin family and exhibits peptidyl-prolyl cis-trans isomerase (PPIase) activity. It participates in various biological processes through the regulation of peptidyl-prolyl isomerization. However, the specific role of CypE in osteoblast differentiation has not yet been elucidated. In this study, we first discovered the positive impact of CypE on osteoblast differentiation through gain or loss of function experiments. Mechanistically, CypE enhances the transcriptional activity of Runx2 through its PPIase activity. Furthermore, we identified the involvement of the Akt signaling pathway in CypE's function in osteoblast differentiation. Taken together, our findings indicate that CypE plays an important role in osteoblast differentiation as a positive regulator by increasing the transcriptional activity of Runx2.

Vacuum-powered soft actuator with oblique air chambers for easy detachment of artificial dry adhesive by coupled contraction and twisting.

A gecko foot-inspired, mushroom-shaped artificial dry adhesive exploiting intermolecular forces between microstructure and surface has drawn research attention for its strong adhesive force. However, the high pull-off strength corresponding to the adhesive force matters when detaching fragile substrates. In this study, we report a vacuum-powered soft actuator having oblique air chambers and a dry adhesive. The soft actuator performs coupled contraction and twisting by applying negative pneumatic pressure inward and exhibits not only high pull-off strength but also easy detachment. This effective detachment can be achieved thanks to the twisting motion of the soft actuator. The detachment performances of the actuator models are assessed using a 6-degrees-of-freedom robot arm. Results show that the soft actuators exhibit remarkable pull-off strength decrement from ~20 N cm-2 to ~2 N cm-2 due to the twisting. Finally, to verify a feasible application of this study, we utilize the inherent compliance of the actuators and introduce a glass transfer system for which a glass substrate on a slope is gripped by the flexibility of the soft actuators and delivered to the destination without any fracture.

Inhibitory Effects of Ehretia tinifolia Extract on the Excessive Oxidative and Inflammatory Responses in Lipopolysaccharide-Stimulated Mouse Kupffer Cells.

Ehretia tinifolia (E. tinifolia) L., an evergreen tree with substantial biological activity, including antioxidant and anti-inflammatory effects, has been used in many herbal and traditional medicines. To elucidate its antioxidant and anti-inflammatory activity and the underlying mechanisms, we applied a methanol extract of E. tinifolia (ETME) to lipopolysaccharide (LPS)-stimulated mouse immortalized Kupffer cells. ETME suppressed the LPS-induced increase in nitric oxide, a mediator for oxidative stress and inflammation, and restored LPS-mediated depletion of total glutathione level by stabilizing antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) and the subsequent increase in heme oxygenase-1 levels. Furthermore, ETME inhibited the LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. The inhibitory effects of ETME on pro-inflammatory responses were regulated by ETME-mediated dephosphorylation of mitogen-activated protein kinases (MAPKs: p38, p44/p42, and stress-associated protein kinase/c-Jun N-terminal kinase) and inhibition of nuclear localization of nuclear factor kappa B (NF-κB). These results suggest that ETME is a possible candidate for protecting Kupffer cells from LPS-mediated oxidative stress and excessive inflammatory responses by activating antioxidant Nrf2/HO-1 and inhibiting pro-inflammatory NF-κB and MAPKs, respectively.