Autophagy and mitophagy-related extracellular mitochondrial dysfunction of cerebrospinal fluid cells in patients with hemorrhagic moyamoya disease.

We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2-ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction.

Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury.

BACKGROUND: We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available. METHODS: The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo study used a stereotaxic impactor to induce a TBI model in C57BL/6 J mice and analyzed immunohistochemical changes and cognitive function after an intraperitoneal injection of oxiracetam (30 mg/kg/day) for 5 days. The number of mice used in this study was 60. They were divided into three groups (sham, TBI, and TBI with oxiracetam treatment) (20 mice in each group). RESULTS: The in vitro study showed that oxiracetam treatment resulted in increased superoxide dismutase (SOD)1 and SOD2 mRNA expression. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and interleukin (IL)-1 ß were decreased after oxiracetam treatment, along with decreases in intracellular reactive oxygen species production and apoptotic effects. TBI mice treated with oxiracetam exhibited the loss of fewer cortical damaged lesions, less brain edema, and fewer Fluoro-Jade B (FJB)-positive and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-positive cells compared to those without oxiracetam treatment. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and IL-1ß were decreased significantly after oxiracetam treatment. These inflammation-related markers, which colocalized with Iba-1-positive or GFAP-positive cells after TBI, were also decreased after oxiracetam treatment. TBI mice treated with oxiracetam had a smaller decrease in preference and more latency time than those not treated with oxiracetam, suggesting the amelioration of impaired cognitive impairment. CONCLUSIONS: Oxiracetam may be helpful in restoring cognitive impairment by ameliorating neuroinflammation in the early phase of TBI.

Acute normovolemic hemodilution for a patient with secondary polycythemia undergoing aortic valve replacement due to severe aortic stenosis - A case report.

BACKGROUND: A high hematocrit level in patients with erythrocytosis is linked with increased blood viscosity and increased risk of thromboembolism. Therefore, it is necessary to adequately lower the hematocrit level before performing a high-risk surgery. CASE: A 67-year-old male was scheduled for aortic valve replacement due to severe aortic stenosis. The preoperative hematocrit level of this patient was very high due to secondary polycythemia by hypoxia. We decided to perform acute normovolemic hemodilution after anesthetic induction to reduce the risk of thromboembolism in the patient. The patient was discharged after a successful surgery and a post-operative period without any side effects. CONCLUSIONS: We estimate that patients with secondary polycythemia may benefit from acute normovolemic hemodilution to reduce their hematocrit levels while undergoing cardiac surgery using cardiopulmonary bypass. However, it is necessary to control the hematocrit level, since a significant decrease can cause side effects.

Disulfide-Containing Crosslinked Polyaniline Cathode for Rechargeable Battery.

Polymer electrodes have had several advantages like being environment friendly, mechanically flexible and more inexpensive than lithium metal which is used as lithium metal oxide-based cathode. But polymer electrodes generally have had lower charge/discharge capacity. Sulfur compounds with organothiol (-SH) or disulfide (S-S) group have advantages about high theoretical capacity but they have poor electronic conductivity. Then in this study, focusing on the enhancement of electrical performance of polymer electrode, disulfide bonds are linked to the side chain of polyaniline (PANI) and conjugated crosslinking between polymer chains is formed. As a result, crosslinked poly(9-amino-5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracene) (PADTTAA)-co-PANI electrodes with different ratio of ADTTAA were successfully synthesized. Elemental and compositional analysis on the surface of the polymer sample was measured by using X-ray photoelectron spectroscopy (XPS). And the electrochemical property of disulfide-containing crosslinked PANI based cathode was investigated by confirming cyclic voltammetry and charge-discharge capacity. As the contents of ADTTAA increased, the charge/discharge capacity increased but the conductivity and cycle life decreased.

Inhaled nitric oxide for the brain dead donor with neurogenic pulmonary edema during anesthesia for organ donation: a case report.

Neurogenic pulmonary edema (NPE) in brain dead organ donors occurring after an acute central nervous system insult threatens organ preservation of potential organ donors and the outcome of organ donation. Hence the active and immediate management of NPE is critical. In this case, a 50-year-old male was admitted to the intensive care unit (ICU) for organ donation. He was hypoxic due to NPE induced by spontaneous intracerebral hemorrhage and intraventricular hemorrhage. Protective ventilatory management, intermittent recruitment maneuvers, and supportive treatment were maintained in the ICU and the operating room (OR). Despite this management, the hypoxemia worsened after the OR admission. So inhaled nitric oxide (NO) therapy was performed during the operation, and the hypoxic phenomena showed remarkable improvement. The organ retrieval was successfully completed. Therefore, NO inhalation can be helpful in the improvement of hypoxemia caused by NPE in brain dead organ donors during anesthesia for the organ donation.

Alteration of the QT variability index in end-stage liver disease.

BACKGROUND: A prolonged QT interval can lead to malignant ventricular arrhythmias and sudden cardiac death, and has frequently been found in end-stage liver disease (ESLD). However, myocardial repolarization lability has not yet been fully investigated. We evaluated the QT variability index (QTVI), a marker of temporal inhomogeneity in ventricular repolarization and an abnormality associated with re-entrant malignant ventricular arrhythmias. We determined whether QTVI is affected by the head-up tilt test in ESLD. METHODS: We assessed 36 ESLD patients and 12 control subjects without overt heart disease before and after the 70-degree head-up tilt test. The electrocardiography signal (lead II) was recorded on a computer with an analog-to-digital converter. The RR interval (RRI) and QT interval were measured after recording 5 min of the digitized electrocardiography. Then, the QT intervals were corrected with Bazett's formula (QTc). QTVI was calculated through the following formula: QTVI = log10 [(QTv/QTm2)/(RRIv/RRIm2)], QTv/RRIv: variance of QTI/RRI, QTm/RRIm: mean of QT interval/RRI. RESULTS: Cirrhotic patients exhibited an elevated QTVI. In particular, Child class C patients had a significantly increased QTVI compared to Child class A patients and the control subjects in the supine position. However, the head-up tilt test did not cause a significant difference in QTVI in relation to the severity of ESLD. CONCLUSIONS: Myocardial repolarization lability was significantly altered in end-stage liver disease. Our data suggest that the severity of ESLD is associated with the degree of the alteration in the QT variability index.

Poly(hydroxyethyl methacrylate) based networked solid polymer electrolyte.

Solid polymer electrolytes (SPEs) have good safety for lithium battery compared to liquid electrolytes, but they have low ionic conductivity. To solve the problem, the polymer-in-salt system was introduced which has higher ionic conductivity than salt-in-polymer system. However, polymer-in-salt system has disadvantages that are poor mechanical properties with increasing salt concentration. In this study, networked polymer electrolytes consisting of poly(hydroxyethyl methacrylate) (P(HEMA)), lithium triflate (LiCF3SO3, LiTf) and hydrochloric acid (HCl) were prepared. And the electrochemical and mechanical properties of P(HEMA) based SPEs were investigated by using ac impedance analyzer and universal testing machine, respectively.

Tumor suppressor p53 plays a key role in induction of both tristetraprolin and let-7 in human cancer cells.

Tristetraprolin (TTP) and let-7 microRNA exhibit suppressive effects on cell growth through down-regulation of oncogenes. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. However, the precise mechanism of this repression is unknown. We here demonstrate that p53 stimulated by the DNA-damaging agent doxorubicin (DOX) induced the expression of TTP in cancer cells. TTP in turn increased let-7 levels through down-regulation of Lin28a. Correspondingly, cancer cells with mutations or inhibition of p53 failed to induce the expression of both TTP and let-7 on treatment with DOX. Down-regulation of TTP by small interfering RNAs attenuated the inhibitory effect of DOX on let-7 expression and cell growth. Therefore, TTP provides an important link between p53 activation induced by DNA damage and let-7 biogenesis. These novel findings provide a mechanism for the widespread decrease in TTP and let-7 and chemoresistance observed in human cancers.