The apolipoprotein E (APOE) gene is the most potent genetic risk factor for dementia. However, there are few studies on how the APOE gene affects cognitive domain functions.
This study aimed to ...investigate the effects of risk factors for dementia on cognitive function in patients with mild cognitive impairment and Alzheimer's disease (AD).
This study included subjects whose Clinical Dementia Rating scores ranged from 0.5 to 2 and who were older than 65 years. Risk factors for dementia included the APOE ɛ4 allele, age, education period, employment period, body mass index, and exercise. APOE genotyping was performed by polymerase chain reaction, and other factors were identified using medical charts or structured checklists. Cognitive function was measured using the Seoul Neuropsychological Screening Battery II.
General cognitive function did not show a significant difference according to APOE ɛ4 status. However, the score for delayed verbal memory was lower in the APOE ɛ4-carrier group than in the non-carrier group (p < 0.05). In addition, age, education period, employment period, and exercise were correlated with different cognitive function domains in the non-carrier group (p < 0.05); however, the carrier group was showed a significant correlation between age, body mass index, and cognitive domains.
Our findings suggest that APOE ɛ4 significantly decreases verbal memory in patients with AD. Moreover, the effects of risk factors on cognitive function were significantly different according to the APOE ɛ4 status.
Abstract Autophagy is a catabolic process involved in cell death and in cell protective mechanism. Autophagic cell death is differentiated from apoptosis by the presence of double or ...multiple-membrane enclosed vesicles, and the ATG proteins are essential for the formation of these autophagic vesicles. Here, we show that ATG6/Beclin-1 is a novel caspase substrate. ATG6 is directly cleaved by caspases in a process inhibited by the pan caspase inhibitor, zVAD. Ectopic expression of ATG6 suppresses cell death while reduction of ATG6 levels by siRNA sensitizes cells to TRAIL-induced cell death. Also, the inhibition of caspases leads to an increase in autophagy. These results suggest that caspase-mediated cleavage of ATG6 links the apoptotic and autophagic signaling pathways.
Renamezin.sup.® is a modified capsule-type oral spherical adsorptive carbon which lowers indoxyl sulfate levels in patients with advanced chronic kidney disease (CKD). This 24-week prospective ...observational cohort study was performed to evaluate the effect of Renamezin.sup.® upon attenuation of renal function decline. A total of 1,149 adult patients with baseline serum creatinine 2.0-5.0 mg/dL were enrolled from 22 tertiary hospital in Korea from April 2016 to September 2018. Among them, a total of 686 patients completed the study and were included in the intention-to-treat analysis. A total of 1,061 patients were included in the safety analysis. The mean age was 63.5 years and male patients were predominant (63.6%). Most of the patients (76.8%) demonstrated high compliance with study drug (6g per day). After 24 week of treatment, serum creatinine was increased from 2.86±0.72 mg/dL to 3.06±1.15 mg/dL (p<0.001), but estimated glomerular filtration rate was not changed significantly during observation period (22.3±6.8 mL/min/1.73m.sup.2 to 22.1±9.1 mL/min/1.73m.sup.2, p = 0.243). Patients with age over 65 years old and those under good systolic blood pressure control <130 mmHg were most likely to get benefit from Renamezin.sup.® treatment to preserve renal function. A total of 98 (9.2%) patients out of 1,061 safety population experienced 134 adverse events, of which gastrointestinal disorders were the most common. There were no serious treatment-related adverse events. Renamezin.sup.® can be used safely to attenuate renal function decline in moderately advanced CKD patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autophagy is associated with cell survival and cell death. Autophagy is implicated in the pathophysiology of various human diseases. In order to identify autophagy regulatory molecules, we screened a ...chemical drug library in SH-SY5Y cells and selected Sertindole as a potent autophagy inducer. Sertindole was developed as an antipsychotic drug for Schizophrenia. Sertindole treatment highly induced the formation of autophagosomes as well as LC3 conversion. Subsequently, Sertindole-induced autophagy was efficiently suppressed by down regulation of ATG5. Sertindole also increased reactive oxygen species (ROS) production, which contributes to autophagy-associated cell death in neuroblastoma cells. ROS scavengers such as N-acetylcysteine and Trolox suppressed not only ROS generation but also autophagy activation by Sertindole. These results suggest Sertindole induces autophagy and autophagy-associated cell death by ROS production in neuroblastoma cells.
The contextual interference (CI) effect of motor skill has been demonstrated through numerous studies. However, few studies have reported on daily living tasks in patients with stroke. This study ...investigated the CI effect on spooning training in such patients. Fourteen right hemiparetic patients with stroke were assigned to one of two groups: a group with a random practice schedule or a group with a blocked practice schedule. The spooning task involved scooping go stones from a bowl 30 cm away in 3 different directions to a bowl in front of the patient. We evaluated the acquisition, retention, and transfer of motor learning for spooning. The transfer was evaluated while participants ate cereal in a bowl with a spoon. Upper extremity function, defined as far-transfer, was also evaluated using the box-and-block test. In the retention test, no significant difference between random and blocked practice groups was shown, although both groups showed differences between pre-test and post-test movement times. However, in the transfer test, the random practice group had a significantly shorter movement time than the blocked practice group and also revealed improvement between the pre- and follow-up tests. Additionally, in the far-transfer test, there were significant differences between the pre- and post-, and pre- and follow-up tests only in the random practice group. These findings show that the benefits of CI for transfer can be applied to the learning of feeding skills in patients with stroke and that although the blocked practice is also partially beneficial to long-lasting skill learning in a treatment setting, it may not be efficient under changed conditions. We also suggest the possibility that feeding training with the CI effect could apply to not only transfer but also to far-transfer.
The authors reveal the mechanisms of degradation of capacity, charge voltage, and discharge voltage of commercially‐available high‐nickel cathode material when it is cycled without a voltage margin ...by two different charge protocols: constant‐current charging and constant‐current, constant‐voltage charging. With repeated constant‐current charging, the cathode material changes to a non‐periodic cation‐mixed state, which causes a relatively low voltage degradation, whereas during constant‐current, constant‐voltage charging, the cathode material changes from a layered structure to a periodic cation‐mixed spinel‐like phase, with consequent severe voltage decay. This decay results from a reduction in the equilibrium electrode potential and an increase of overpotential which are aggravated in a periodic cation‐mixed state. The findings provide insights into the use of excess Li without charge‐voltage margin in high‐Ni cathode materials.
Constant voltage step at high voltage (4.3 V) entails periodic cation‐mixed states in high‐nickel cathode materials which leads to severe voltage decay. Thus, constant voltage step at high voltage should be avoided for high‐nickel cathode materials. More fundamentally, structural stability of high‐nickel cathode materials should be improved to alleviate lattice distortion induced by the phase transition between two hexagonal phases.
Despite their exceptionally high capacity, overlithiated layered oxides (OLO) have not yet been practically used in lithium‐ion battery cathodes due to necessary toxic/complex chemical activation ...processes and unsatisfactory electrochemical reliability. Here, a new class of ecofriendly chemical activation strategy based on amphiphilic deoxyribose nucleic acid (DNA)‐wrapped multiwalled carbon nanotubes (MWCNT) is demonstrated. Hydrophobic aromatic bases of DNA have a good affinity for MWCNT via noncovalent π–π stacking interactions, resulting in core (MWCNT)‐shell (DNA) hybrids (i.e., DNA@MWCNT) featuring the predominant presence of hydrophilic phosphate groups (coupled with Na+) in their outmost layers. Such spatially rearranged Na+–phosphate complexes of the DNA@MWCNT efficiently extract Li+ from monoclinic Li2MnO3 of the OLO through cation exchange reaction of Na+–Li+, thereby forming Li4Mn5O12‐type spinel nanolayers on the OLO surface. The newly formed spinel nanolayers play a crucial role in improving the structural stability of the OLO and suppressing interfacial side reactions with liquid electrolytes, eventually providing significant improvements in the charge/discharge kinetics, cyclability, and thermal stability. This beneficial effect of the DNA@MWCNT‐mediated chemical activation is comprehensively elucidated by an in‐depth structural/electrochemical characterization.
DNA‐wrapped multiwalled carbon nanotubes (MWCNT) (DNA@MWCNT) are presented as an ecofriendly chemical activation strategy for overlithiated layered oxides (OLO) cathode materials. The Li4Mn5O12‐type spinel nanolayers are formed on the OLO surface through a cation exchange reaction of Na+ (from phosphate complexes of DNA@MWCNT)–Li+ (from OLO). The spinel nanolayers significantly improve the charge–discharge kinetics, cyclability, and thermal stability. This unique behavior is comprehensively investigated by in‐depth structural/electrochemical characterization.
Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, ...and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Biliary intraepithelial neoplasia (BilIN) is the most common noninvasive precursor lesion which progresses to cholangiocarcinoma (CC) and is often found synchronously adjacent to the tumor or at the ...surgical resection margin. The aim of this study was to elucidate the prevalence and prognostic effect of BilIN on survival after resection for CC. We retrospectively analyzed the database of patients with CC who underwent surgery performed at our institution from 2010 to 2017. There were 142 patients who underwent surgery for CC. BilIN was detected in 42 patients (29.5%). On univariate analysis, extrahepatic CC (ExtraH CC) patients with BilIN lesions significantly showed better disease-free survival (P = 0.05). Also, although not statistically significant, ExtraH CC patients with BilIN lesions revealed better overall survival (OS) (P = 0.09). On multivariate analysis, presence of BilIN lesion, irrespective of location, was significantly associated with better disease-free survival (HR = 2.059, 95% confidence interval (CI): 1.057–4.432, P = 0.041) and OS (HR = 1.831, 95% CI: 1.149–3.534, P = 0.044) in ExtraH CC patients. The presence of BilIN lesions was not uncommon in CC patients and was significantly associated with better disease-free survival and OS in ExtraH CC patients. However, larger studies with longer follow-up are needed to accurately determine its clinical significance.
Circulating tumor cells (CTCs) in the blood have been used as diagnostic markers in patients with colorectal cancer (CRC). In this study, we evaluated a CTC detection system based on cell size to ...assess CTCs and their potential as early diagnostic and prognostic biomarkers for CRC.
From 2014 to 2015, 88 patients with newly diagnosed CRC, who were scheduled for surgery, and 31 healthy volunteers were enrolled and followed up in Pusan National University Hospital. CTCs were enriched using a centrifugal microfluidic system with a new fluid-assisted separation technique (FAST) and detected by cytomorphological evaluation using fluorescence microscopy.
Two or more CTCs were detected using FAST in 74 patients and 3 healthy volunteers. The number of CTCs in the CRC group was significantly higher than that in the healthy volunteers (P < 0.001). When a receiver operating characteristic curve was created to differentiate patients with CRC from healthy volunteers, the sensitivity and specificity were almost optimized when the critical CTC value was 5/7.5 mL of blood. When this value was used, the sensitivity and specificity in differentiating patients with CRC from the healthy controls were 75% and 100%, respectively. In patients with CRC with ≥5 CTCs, vascular invasion was frequently identified (P = 0.035). All patients with stage IV were positive for CTCs. Patients with ≥5 CTCs showed a trend toward poor overall and progression-free survival.
Our study demonstrated promising results with the use of FAST-based CTC detection for the early diagnosis and prognosis of CRC.
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