MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease

BackgroundAlzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum.MethodWe included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit.ResultsPairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026).ConclusionPlasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT03370744

Study on the Molecular Mechanisms of dlk1 Stimulated Lung Cancer Cell Proliferation

Background and objective The imprinted gene dlk1 has been recognized as a cancer related gene since it aberrantly expressed in a series of cancer tissues, but its role in lung cancer is still unknown. The aim of this study is to examine dlk1’s expression in non-small cell lung cancers (NSCLCs) and investigate the molecular mechanism by which dlk1 could accelerate the proliferation of the cells in lung cancer cell lines (H520). Methods The relative expression of dlk1 among 30 NSCLC specimens and their adjacent normal lung tissues were analyzed by RT-PCR. A cell model that stably expressed exogenous dlk1 was established following that the dlk1 gene was cloned into a eukaryotic expression vector and then transfected into the lung cancer cells H520. CCK8 analysis and colony forming assay were employed to investigate the effect of dlk1 on cell proliferation. The expression of CyclinB1 was detected by Western blot. Results dlk1 aberrantly expressed in 36.7% (11/30) of the tumor tissues of NSCLC compared with their adjacent cancer lung tissues. CCK8 analysis showed that overexpression of dlk1 could promote the proliferation of H520 cells (P < 0.05) and the results was further confirmed by colony forming assay. Western blot analysis found that over expression of dlk1 could up-regulate the expression of CyclinB1 (P < 0.05). Conclusion dlk1 aberrantly expressed in NSCLCs. The Overexpression of dlk1 could accelerate the proliferation of lung cancer cells H520 in vitro, probably through up-regulating the expression of cell cycle protein CyclinB1

Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

Vestibular and Non-vestibular Contributions to Eye Movements that Compensate for Head Rotations during Viewing of Near Targets

We studied horizontal eye movements induced by en-bloc yaw rotation, over a frequency range 0.2 - 2.8 Hz, in 10 normal human subjects as they monocularly viewed a target located at their near point of focus. We measured gain and phase relationships between eye-in-head velocity and head velocity when the near target was either earth-fixed or head-fixed. During viewing of the earth-fixed near target, median gain was 1.49 (range 1.24 - 1.87) at 0.2 Hz for the group of subjects, but declined at higher frequencies, so that at 2.8 Hz median gain was 1.08 (range 0.68 - 1.67). During viewing of the head-fixed near target , median gain was 0.03 (range 0.01 - 0.10) at 0.2 Hz for the group of subjects, but increased at higher frequencies, so that at 2.8 Hz median gain was 0.71 (range 0.28 - 0.94). We estimated the vestibular contribution to these responses vestibulo-ocular reflex gain (Gvor) by applying transient head perturbations (peak acceleration> 1,000 deg/s(exp 2)) during sinusoidal rotation under the two viewing conditions. Median Gvor, estimated < 70ms after the onset of head perturbation, was 0.98 (range 0.39 - 1.42) while viewing the earth-fixed near target, and 0.97 (range 0.37 - 1.33) while viewing the head-fixed near target. For the group of subjects, 9 out of 10 subjects showed no significant difference of Gvor between the two viewing conditions ( p > 0.053 ) at all test frequencies. Since Gvor accounted for only -73% of the overall response gain during viewing of the earth-fixed target, we investigated the relative contributions of non-vestibular factors. When subjects viewed the earth-fixed target under strobe illumination, to eliminate retinal image slip information, the gain of compensatory eye movements declined compared with viewing in ambient room light. During sum-of-sine head rotations, while viewing the earth-fixed target, to Han et al./VOR during near-viewing minimize contributions from predictive mechanisms, gain also declined Nonetheless, simple superposition of smooth-pursuit tracking of sinusoidal target motion could not fully account for the overall response at higher frequencies, suggesting other nonvestibular contributions. During binocular viewing conditions when vergence angle was significantly greater than monocular viewing (p < 0.00l), the gain of compensatory eye movements did not show proportional change; indeed, gain could not be correlated with vergence angle during monocular or binocular viewing. We conclude that several separate factors contribute to generate eye rotations during sinusoidal yaw head rotations while viewing a near target; these include the VOR, visual-tracking eye movements that utilize retinal image motion, predictive eye movements and, possibly, other unidentified non-vestibular factors. For these experiments, vergence was not an important determinant of response gam

Impacts of LaOx Doping on the Performance of ITO/Al₂O₃/ITO Transparent RRAM Devices

Fully transparent ITO/LaAlO3/ITO structure RRAM (resistive random access memory) devices were fabricated on glass substrate, and ITO/Al2O3/ITO structure devices were set for comparison. The electrical characteristics of the devices were analyzed by Agilent B1500A semiconductor analyzer. Compared with the ITO/Al2O3/ITO RRAM devices, the current stability, SET/RESET voltage distribution, and retention characteristic of the ITO/LaAlO3/ITO RRAM devices have been greatly improved. In the visible light range, the light transmittance of the device is about 80%, that of the LaAlO3 layer is about 95%, the on-off ratio of the device is greater than 40, and the data retention time is longer than 10,000 s. The devices have great optical and electrical properties and have huge application potential as fully transparent RRAM devices

Hsp90AB1 Protein is Overexpressed in Non-small Cell Lung Cancer Tissues and Associated with Poor Prognosis in Lung Adenocarcinoma Patients

Background and objective Heat shock protein 90 kDa alpha, class B member 1 (Hsp90AB1) is highly conserved ATP-dependent molecular chaperone, and over-expressed in a variety of tumor cells. Some molecules that play important roles in tumor development signaling pathways such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2) are Hsp90AB1 client proteins. Hsp90AB1 interact with these client proteins and participate in a variety of pathophysiological processes of cells. The aim of this study is to detect the expression of Hsp90AB1 in non-small cell lung cancer (NSCLC) tissues, and explore its clinical significance. Methods The expression of Hsp90AB1 in 213 NSCLC tissues and 147 normal lung tissues was detected by tissue microarray and immunohistochemical staining method, and the relationship of Hsp90AB1 expression with clinicopathological parameters and prognosis of NSCLC patients were analyzed. Results The expression level of Hsp90AB1 in lung cancer tissues (positive rate of 54.0%) was significantly higher than that in normal lung tissue (positive rate of 0.0%, P0.05). Conclusion Hsp90AB1 protein was over-expressed in NSCLC tissues, and was associated with lung cancer pathological type and overall survival in lung adenocarcinoma patients

Fabrication and Characterization of MoS2/h-BN and WS2/h-BN Heterostructures

The general preparation method of large-area, continuous, uniform, and controllable vdW heterostructure materials is provided in this paper. To obtain the preparation of MoS2/h-BN and WS2/h-BN heterostructures, MoS2 and WS2 material are directly grown on the insulating h-BN substrate by atmospheric pressure chemical vapor deposition (APCVD) method, which does not require any intermediate transfer steps. The test characterization of MoS2/h-BN and WS2/h-BN vdW heterostructure materials can be accomplished by optical microscope, AFM, Raman and PL spectroscopy. The Raman peak signal of h-BN material is stronger when the h-BN film is thicker. Compared to the spectrum of MoS2 or WS2 material on SiO2/Si substrate, the Raman and PL spectrum peak positions of MoS2/h-BN heterostructure are blue-shifted, which is due to the presence of local strain, charged impurities and the vdW heterostructure interaction. Additionally, the PL spectrum of WS2 material shows the strong emission peak at 1.96 eV, while the full width half maximum (FWHM) is only 56 meV. The sharp emission peak indicates that WS2/h-BN heterostructure material has the high crystallinity and clean interface. In addition, the peak position and shape of IPM mode characteristic peak are not obvious, which can be explained by the Van der Waals interaction of WS2/h-BN heterostructure. From the above experimental results, the preparation method of heterostructure material is efficient and scalable, which can provide the important support for the subsequent application of TMDs/h-BN heterostructure in nanoelectronics and optoelectronics