Toward digitally screening and profiling AD: A GAMLSS approach of MemTrax in China.

PURPOSES: To establish a normative range of MemTrax (MTx) metrics in the Chinese population. METHODS: The correct response percentage (MTx-%C) and mean response time (MTx-RT) were obtained and the composite scores (MTx-Cp) calculated. Generalized additive models for location, shape and scale (GAMLSS) were applied to create percentile curves and evaluate goodness of fit, and the speed-accuracy trade-off was investigated. RESULTS: 26,633 subjects, including 13,771 (51.71%) men participated in this study. Age- and education-specific percentiles of the metrics were generated. Q tests and worm plots indicated adequate fit for models of MTx-RT and MTx-Cp. Models of MTx-%C for the low and intermediate education fit acceptably, but not well enough for a high level of education. A significant speed-accuracy trade-off was observed for MTx-%C from 72 to 94. CONCLUSIONS: GAMLSS is a reliable method to generate smoothed age- and education-specific percentile curves of MTx metrics, which may be adopted for mass screening and follow-ups addressing Alzheimer's disease or other cognitive diseases. HIGHLIGHTS: GAMLSS was applied to establish nonlinear percentile curves of cognitive decline. Subjects with a high level of education demonstrate a later onset and slower decline of cognition. Speed-accuracy trade-off effects were observed in a subgroup with moderate accuracy. MemTrax can be used as a mass-screen instrument for active cognition health management advice.

Structure Identification of ViceninII Extracted from Dendrobium officinale and the Reversal of TGF-ß1-Induced Epithelial⁻Mesenchymal Transition in Lung Adenocarcinoma Cells through TGF-ß/Smad and PI3K/Akt/mTOR Signaling Pathways.

ViceninII is a naturally flavonoid glycoside extracted from Dendrobium officinale, a precious Chinese traditional herb, has been proven to be valuable for cancer treatment. Transforming growth factor-ß1 (TGF-ß1), promotes the induction of epithelial⁻mesenchymal transition (EMT), a process involved in the metastasis of cells that leads to enhanced migration and invasion. However, there is no previously evidence that ViceninII has an inhibitory effect on cancer metastasis, specifically on the TGF-ß1-induced EMT process in lung adenocarcinoma cells. In this experiment, we used UV, ESIMS, and NMR to identify the structure of ViceninII.A549 and H1299 cells were treated with TGF-ß1 in the absence and presence of ViceninII, and subsequent migration and invasion were measured by wound-healing and transwell assays. The protein localization and expressions were detected by immunofluorescence and Western blotting. The results indicated that TGF-ß1 induced spindle-shaped changes, increased migration and invasion, and upregulated or downregulated the relative expression of EMT biomarkers. Meanwhile, these alterations were significantly inhibited when co-treated with ViceninII and inhibitors LY294002 and SB431542. In conclusion, ViceninII inhibited TGF-ß1-induced EMT via the deactivation of TGF-ß/Smad and PI3K/Akt/mTOR signaling pathways.This is the first time that the anti-metastatic effects of ViceninII have been demonstrated, and their molecular mechanisms provided.

Rosmarinic acid protects on rat bone marrow mesenchymal stem cells from hydrogen peroxide-induced apoptosis.

To investigate the anti-oxidant activities and mechanism of rosmarinic acid (RA) on rat bone marrow mesenchymal stem cells (rBMSCs) from ischemia-induced apoptosis in vitro, which was established using H2O2-damage and analyzed for cell viability, cell apoptosis, ROS, morphological changes, and levels of apoptosis proteins. Pretreatment with RA significantly suppressed the generation of ROS, protected the morphological changes of cells, decrease the ratio of cell apoptosis, down-regulated the level of caspase-3, caspase-9, Bax/Bcl-2, and up-regulated the level of p-PI3K. These findings suggest that RA may protect rBMSCs from H2O2-induced apoptosis by partly regulating PI3K/Akt signaling pathway and can be developed as a potential anti-apoptotic agent for therapy in cardiovascular diseases.

Sarcandra glabra (Caoshanhu) protects mesenchymal stem cells from oxidative stress: a bioevaluation and mechanistic chemistry.

BACKGROUND: Sarcandra glabra (Caoshanhu) is a traditional Chinese herbal medicine used for treating various oxidative-stressed diseases. The present work evaluated its protective effect on mesenchymal stem cells (MSCs) from oxidative stress and then discussed possible mechanisms underlying this observation. METHODS: Ethanolic extract of S. glabra (ESG) was investigated by chemical methods for its content of total phenolics, rosmarinic acid, and astilbin. ESG, along with rosmarinic acid and astilbin, was investigated for the effect on the viability of Fenton-treated MSCs using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The observed cell protective effect was further explored by mechanistic chemistry using various antioxidant assays, including DNA protection, •OH-scavenging, •O2--scavenging, FRAP (ferric ion reducing antioxidant power), ABTS+•-scavenging, DPPH•-scavenging, and Fe2+-chelating assays. RESULTS: Analysis of ESG revealed a content of 46.31 ± 0.56 mg quercetin/g total phenolics, 0.78 ± 0.01 % rosmarinic acid, and 3.37 ± 0.01 % astilbin. Results from the MTT assay revealed that three compounds (rosmarinic acid>astilbin>ESG) could effectively increase the survival of Fenton-treated MSCs. Similarly, in •O2--scavenging, DPPH•-scavenging, and Fe2+-chelating assays, rosmarinic acid exhibited more activity than astilbin; while in FRAP, ABTS+•-scavenging assays, astilbin was stronger than rosmarinic acid. CONCLUSION: S. glabra can prevent MSCs from •OH-induced oxidative stress. Such protective effect can be attributed to its antioxidant ability and the presence of two kinds of phytophenols, i.e. caffeoyl derivatives and flavonoids. As the respective representatives of caffeoyl derivatives and flavonoids, rosmarinic acid and astilbin may exert the antioxidant action via direct ROS-scavenging and indirect ROS-scavenging (i.e. Fe2+-chelating). The direct ROS-scavenging ability involves hydrogen atom transfer (HAT) and/or electron transfer (ET) pathway. Astilbin engages the latter pathway more, which can be attributed to the larger planar conjugation in A/C fused rings. Rosmarinic acid, on the other hand, shows more HAT and Fe2+-chelating potential, which may be due to rosmarinic acid bearing one more catechol moiety whereas astilbin has steric-hindrance from 3-α-L-rhamnose and an H-bonding between 4,5 sites. The antioxidant features of rosmarinic acid can be generalized to other caffeoyl derivatives, while that of astilbin cannot be generalized to other flavonoids because of the difference in chemical structures.

Protective Effect of Sinapine against Hydroxyl Radical-Induced Damage to Mesenchymal Stem Cells and Possible Mechanisms.

As a phenolic alkaloid occurring in Cruciferous plants, sinapine was observed to protect mesenchymal stem cells (MSCs) against ·OH-induced damage in this study. It was also found to prevent DNA from damage, to scavenge various free radicals (·OH, ·O2(-), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt) (ABTS)(+·), and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)), and to reduce Cu(2+) to Cu(+). To further explore the mechanism, the end-product of sinapine reaction with DPPH· was determined using HPLC-electrospray ionization (ESI)-MS/MS and HPLC-diode array detector (DAD). Four molecular ion peaks (m/z 701, 702, 703, and 351) in HPLC-ESI-MS/MS analysis indicated a radical adduct formation (RAF) pathway; while a bathochromic shift (λ(max) 334→475 nm) in HPLC-DAD indicated the formation of quinone as the oxidized product of the phenolic -OH group. Based on these results, it may be concluded that, (i) sinapine can effectively protect against ·OH-induced damage to DNA and MSCs; such protective effect may provide evidence for a potential role for sinapine in MSC transplantation therapy, and be responsible for the beneficial effects of Cruciferous plants. (ii) The possible mechanism for sinapine to protect against ·OH-induced oxidative damage is radical-scavenging, which is thought to be via hydrogen atom (H·) transfer (HAT) (or sequential electron (e) proton transfer (SEPT))→RAF pathways.

Purification, Characterization and Biological Activity of Polysaccharides from Dendrobium officinale.

Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of DOPA-1 and DOPA-2 were 394 kDa and 362 kDa, respectively. They were mainly composed of d-mannose, d-glucose, and had a backbone consisting of 1,4-linked ß-d-Manp and 1,4-linked ß-d-Glcp with O-acetyl groups. Bioactivity studies indicated that both DOPA and its purified fractions (DOPA-1 and DOPA-2) could activate splenocytes and macrophages. The D. officinale polysaccharides had stimulatory effects on splenocytes, T-lymphocytes and B-lymphocytes, promoting the cell viability and NO production of RAW 264.7 macrophages. Furthermore, DOPA, DOPA-1 and DOPA-2 were found to protect RAW 264.7 macrophages against hydrogen peroxide (H2O2)-induced oxidative injury by promoting cell viability, suppressing apoptosis and ameliorating oxidative lesions. These results suggested that D. officinale polysaccharides possessed antioxidant activity and mild immunostimulatory activity.

Identification and Validation of Oxidative Stress-Related Biomarkers for Bronchopulmonary Dysplasia.

The objective of this study was to identify and characterize oxidative stress (OS)-related biomarkers in bronchopulmonary dysplasia (BPD) through a combination of bioinformatics analyses and wet experiments. The study utilized the Gene Expression Omnibus database to obtain the mRNA expression profile dataset GSE32472. Differential expression analysis and functional enrichment analysis were employed to investigate the role of OS-related genes in BPD. Gene Ontology Function Enrichment Analysis and Gene Set Enrichment Analysis were conducted to understand the mechanisms behind the signature. Protein-protein interaction analysis to identify hub genes in BPD, and predictions were made for microRNAs (miRNAs), transcription factors (TFs), and potential medications targeting these genes. CIBERSORT was utilized to investigate the correlation between hub genes and the infiltration of immune cells. Hub genes were ultimately determined and confirmed using expression analysis, correlation analysis, receiver operating characteristic (ROC) analysis, and quantitative real-time PCR (qRT-PCR). A novel OS-related gene signature (ARG1, CSF3R, IL1R1, IL1R2, MMP9, RETN, S100A12, and SOCS3) was constructed for the prediction of BPD. We identified 18 miRNAs, 14 TFs, and 30 potential medications targeting these genes. ROC analysis further validated that these genes could diagnose BPD with high specificity and sensitivity. The qRT-PCR revealed that IL1R1 and ARG1 were highly expressed in the lung tissue of the model group, while the expressions of RETN, SOCS3, IL1R2, and MMP9 were decreased. This study demonstrated that ARG1, CSF3R, IL1R1, IL1R2, MMP9, RETN, S100A12, and SOCS3 may serve as potential diagnostic biomarkers in BPD. Furthermore, a significant association between IL1R1 and the pathogenesis of BPD is observed.

The impact of work environment on caring behavior among Chinese hospice nurses: the chain mediating effect of psychological capital and empathy.

Introduction: The caring behavior of hospice nurses toward patients positively impacts their professional careers and significantly improves the quality of hospice services. A positive and supportive work environment may protect nurses against negative emotions that may affect the humanistic care they provide, and their job satisfaction. This study aimed to explore the impact of the nursing work environment on caring behavior. We also investigated the chain mediating effect of psychological capital and empathy on this relationship among Chinese hospice nurses. Methods: The Practice Environment Scale (PES), the Psychological Capital Questionnaire (PCQ), the Empathy Ability Scale for Hospice Nurses, and the Caring Behaviors Inventory (CBI) were used to survey 393 Chinese hospice nurses. SPSS 27.0 and Mplus 8.0 were used for statistical processing to analyze the mediating effects. Results: The nursing work environment positively predicted caring behavior. Furthermore, it was found that psychological capital and empathy jointly mediate the relationship between the nursing work environment and caring behavior. Conclusion: This study reveals how the nursing work environment affects the caring behavior of hospice nurses. Hospital managers need to provide hospice nurses with a favorable working environment from the perspective of positive psychology, continuously monitor their psychological state, improve their caring behavior, and provide references for developing intervention plans to promote the caring behavior of hospice nurses in the future.

[Study on the fingerprint of Morus alba from different habitats by HPLC].

OBJECTIVE: To establish HPLC fingerprint of Morus alba from different habitats by HPLC and provide basis for its quality control. METHODS: HPLC analysis was performed on an Agilent XDB C18 Column (4.6 mm x 250 mm, 5 microm), gradient eluted composed of acetonitrile and 0.3% phosphate acid. The column temperature was set at 35 degrees C and the flow rate was 0.5 mL/min. The detective wavelength was 290 nm. The HPLC fingerprint for 10 batches of Morus alba was studied on their similarity. RESULTS: There were twelve common peaks in the fingerprint. The similarity of 7 batches was above 0.9 and the other batches had low similarity. CONCLUSION: The HPLC fingerprint can be used for quality control of Morus alba with high characteristics and specificity.

Physicochemical and Antioxidant Properties of the Degradations of Polysaccharides from Dendrobium officinale and Their Suitable Molecular Weight Range on Inducing HeLa Cell Apoptosis.

Different molecular weight polysaccharides of Dendrobium officinale (DOPs) have gradually attracted attention because of their broad biological activities. They, however, remain poorly defined whether their antitumor activity is associated with molecular weight. In this study, the physicochemical, antioxidant, and antitumor properties of DOPs, including the crude polysaccharide (DOP) and its six degradation fractions (DOP1-DOP6) extracted from Dendrobium officinale, were determined. Consequently, DOPs were mainly composed of different ratios of mannose and glucose as follows: 5.15 : 1, 4.62 : 1, 4.19 : 1, 4.46 : 1, 4.32 : 1, 4.29 : 1, and 4.23 : 1, and their molecular weights were significantly different ranging from 652.29 kDa to 11.10 kDa. With the concentration increase of DOPs, the scavenging capacity against OH and DPPH free radicals increased. The antitumor ability of DOPs was different that DOP1-DOP5 (Mw: 176.29 kDa-28.48 kDa) exhibited the best antiproliferation activity than DOP (Mw: 652.29 kDa) and DOP6 (Mw: 11.10 kDa) in HeLa cells rather than PC9, A549, and HepG2 cells. Moreover, it is worth mentioning that DOP1 and DOP5 showed stronger capability on inducing apoptosis of HeLa cells than DOP and DOP6 via the mitochondrial pathway by upregulating the ratio of the Bax/Bal-2 mRNA expression. The results demonstrated that DOPs can be used as the potential natural antioxidant and antitumor products in pharmaceutical industries, and the molecular weight is a crucial influential factor of their antitumor activity that 28.48 kDa-176.29 kDa is a suitable range we may refer to.

Protective effect of gigantol against hydrogen peroxide­induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway.

Bone marrow mesenchymal stem cell (BMSC) transplants are promising for the treatment of certain central nervous system diseases. However, oxidative stress is one of the major factors that may limit the survival of the transplanted BMSCs. The present study investigated the effect of pretreatment with gigantol on hydrogen peroxide (H2O2)­induced apoptosis in rat BMSCs (rBMSCs) and the potential underlying mechanisms. The results demonstrated that gigantol pretreatment significantly inhibited H2O2­induced apoptosis of rBMSCs. rBMSCs were incubated with 600 µM H2O2 in the absence or presence of different doses of gigantol (1­100 µM). Cell viability and apoptosis ratios were assessed by MTT assays and flow cytometry, respectively. Morphological alterations and reactive oxygen species were measured by the fluorescent­based methods of Hoechst staining and dichlorodihydrofluorescein diacetate, respectively. Furthermore, the protein levels of phosphorylated­protein kinase B (Akt), B­cell lymphoma­2 (Bcl­2), Bcl­2­associated X (Bax), caspase­3 and caspase­9 were investigated by western blotting. Following incubation with H2O2 for 2 h, gigantol significantly inhibited the H2O2­induced reductions in the cell viability of rBMSCs in a dose­dependent manner. Furthermore, gigantol upregulated Akt phosphorylation and Bcl­2 expression, downregulated Bax expression, and reduced the expression of caspase­3 and caspase­9 in H2O2­treated rBMSCs, whereas an opposite effect was detected when LY294002, an inhibitor of phosphatidylinositol 3­kinase, was administered in combination with gigantol. These results indicate that gigantol may be developed as a promising neuroprotective agent for successful MSC transplantation in ischemic diseases.

The measurement of the effect on citation inequality of differences in citation practices across scientific fields.

This paper has two aims: (i) to introduce a novel method for measuring which part of overall citation inequality can be attributed to differences in citation practices across scientific fields, and (ii) to implement an empirical strategy for making meaningful comparisons between the number of citations received by articles in 22 broad fields. The number of citations received by any article is seen as a function of the article's scientific influence, and the field to which it belongs. A key assumption is that articles in the same quantile of any field citation distribution have the same degree of citation impact in their respective field. Using a dataset of 4.4 million articles published in 1998-2003 with a five-year citation window, we estimate that differences in citation practices between the 22 fields account for 14% of overall citation inequality. Our empirical strategy is based on the strong similarities found in the behavior of citation distributions. We obtain three main results. Firstly, we estimate a set of average-based indicators, called exchange rates, to express the citations received by any article in a large interval in terms of the citations received in a reference situation. Secondly, using our exchange rates as normalization factors of the raw citation data reduces the effect of differences in citation practices to, approximately, 2% of overall citation inequality in the normalized citation distributions. Thirdly, we provide an empirical explanation of why the usual normalization procedure based on the fields' mean citation rates is found to be equally successful.