Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects.</p> <p>Methods</p> <p>We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia.</p> <p>Results</p> <p>We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group.</p> <p>Conclusion</p> <p>These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD.</p

Serum immunoglobulin fused interferon-α inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 × : 30 µg/kg and 50 × : 150 µg/kg). A slight anti-tumoral effect was observed in all 10 × groups compared to the control. In the 50 × groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-β. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition

Mesoscale magnetism at the grain boundaries in colossal magnetoresistive films

We report the discovery of mesoscale regions with distinctive magnetic properties in epitaxial La$_{1-x}$Sr$_{x}$MnO$_{3}$ films which exhibit tunneling-like magnetoresistance across grain boundaries. By using temperature-dependent magnetic force microscopy we observe that the mesoscale regions are formed near the grain boundaries and have a different Curie temperature (up to 20 K {\it higher}) than the grain interiors. Our images provide direct evidence for previous speculations that the grain boundaries in thin films are not magnetically and electronically sharp interfaces. The size of the mesoscale regions varies with temperature and nature of the underlying defect.Comment: 4 pages of text, 4 figure

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria

Background/Aim This study aimed to determine the diagnostic performance of 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) imaging criteria compared with the 2018 KLCA-NCC for hepatocellular carcinoma (HCC) in high-risk patients using magnetic resonance imaging (MRI). Methods This retrospective study included 415 treatment-naïve patients (152 patients who underwent extracellular contrast agent [ECA]-MRI and 263 who underwent hepatobiliary agent [HBA]-MRI; 535 lesions, including 412 HCCs) with a high risk of HCC who underwent contrast-enhanced MRI. Two readers evaluated all lesions according to the 2018 and 2022 KLCA-NCC imaging diagnostic criteria, and the per-lesion diagnostic performances were compared. Results In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI showed a significantly higher sensitivity for the diagnosis of HCC than ECA-MRI (77.0% vs. 64.3%, P=0.006) without a significant difference in specificity (94.7% vs. 95.7%, P=0.801). On ECAMRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC had significantly higher sensitivity than those of the 2018 KLCA-NCC (85.3% vs. 78.3%, P=0.002) with identical specificity (93.6%). On HBA-MRI, the sensitivity and specificity of “definite” or “probable” HCC categories of both 2018 and 2022 KLCA-NCC were not significantly different (83.3% vs. 83.6%, P>0.999 and 92.1% vs. 90.8%, P>0.999, respectively). Conclusions In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI provides better sensitivity than ECA-MRI without compromising specificity. On ECA-MRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC may improve sensitivity in the diagnosis of HCC compared with the 2018 KLCA-NCC

Phenotypic Characterization of Transgenic Miscanthus sinensis Plants Overexpressing Arabidopsis Phytochrome B

Phytochromes are dimeric pigment proteins with reversible photochromism between red and far-red light-absorbing forms. They are photoreceptors that regulate various aspects of plant growth and development and have been used for biotechnological applications to improve agricultural performance of crops. Miscanthus species have been suggested as one of the most promising energy crops. In this paper, Arabidopsis phytochrome B (PHYB) gene was introduced into Miscanthus sinensis using Agrobacteriummediated transformation method that we developed recently, with the herbicide resistance gene (BAR) as a selection marker. After putative transgenic plants were selected using the herbicide resistance assay, genomic integration of the transgene was confirmed by genomic PCR and Southern blot analysis, and transgene expression was validated by Northern blot analysis. Compared to nontransformed control plants, transgenic plants overexpressing PHYB showed phenotypes with increased phytochrome B function, which includes increased chlorophyll content, decreased plant height, and delayed flowering. Therefore, these results suggest that Arabidopsis phytochrome B is functional in M. sinensis and provide a method to develop Miscanthus varieties with enhanced agricultural performance using phytochromes

Lapatinib, a Dual EGFR and HER2 Tyrosine Kinase Inhibitor, Downregulates Thymidylate Synthase by Inhibiting the Nuclear Translocation of EGFR and HER2

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been shown to exert a synergistic antitumor effect when combined with fluoropyrimidine. This synergy may be attributable to the downregulation of thymidylate synthase (TS), which is frequently overexpressed in fluoropyrimidine-resistant cancer cells. However, the molecular mechanism underlying the downregulation of TS has yet to be clearly elucidated.In this study, we demonstrate that lapatinib, a dual TKI of EGFR and HER2 downregulates TS via inhibition of the nuclear translocation of EGFR and HER2. From our cDNA microarray experiments, we determined that a variety of nucleotide synthesis-related genes, including TS, were downregulated with lapatinib, and this was apparent in HER2-amplified cells. Targeted and pharmacologic inhibition assays confirmed that the dual inhibition of EGFR and HER2 is required for the more effective reduction of TS as compared to what was observed with gefitinib or trasutuzumab alone. Additionally, we determined that co-transfected EGFR and HER2 activate the TS gene promoter more profoundly than do either EGFR or HER2 alone. The translocation of EGFR and HER2 into the nucleus and the subsequent activation of the TS promoter were inhibited by lapatinib.These results demonstrate that lapatinib inhibits the nuclear translocation of EGFR and HER2 and downregulates TS, thus sensitizing cancer cells to fluoropyrimidine

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods

Shared psychological characteristics that are linked to aggression between patients with Internet addiction and those with alcohol dependence

Background : Internet addiction (IA) is considered as one of behavioral addictions. Although common neurobiological mechanisms have been suggested to underlie behavioral addiction and substance dependence, few studies have directly compared IA with substance dependence, such as alcohol dependence (AD). Methods : We compared patients with IA, AD, and healthy controls (HC) in terms of the Five Factor Model of personality and with regard to impulsiveness, anger expression, and mood to explore psychological factors that are linked to aggression. All patients were treatment-seeking and had moderate-to-severe symptoms. Results : The IA and AD groups showed a lower level of agreeableness and higher levels of neuroticism, impulsivity, and anger expression compared with the HC group, which are characteristics related to aggression. The addiction groups showed lower levels of extraversion, openness to experience, and conscientiousness and were more depressive and anxious than the HCs, and the severity of IA and AD symptoms was positively correlated with these types of psychopathology. Conclusions : IA and AD are similar in terms of personality, temperament, and emotion, and they share common characteristics that may lead to aggression. Our findings suggest that strategies to reduce aggression in patients with IA are necessary and that IA and AD are closely related and should be dealt with as having a close nosological relationship.This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI12C-0113-020013).Peer Reviewe